View source for Modafinil

{{Short description|Eugeroic medication}}
{{Use American English|date=December 2023}}
{{Use mdy dates|date=March 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = correct
| Watchedfields = correct
| verifiedrevid = 800497129
| image = Marvin image (9).png
| image_class = skin-invert-image
| width = 300
| alt = 
| caption = 
| image2 = (S)-Modafinil molecule ball.png
| image_class2 = bg-transparent
| alt2 = <!-- Clinical data -->
| pronounce = 
| tradename = Provigil, others
| Drugs.com = {{drugs.com|monograph|modafinil}}
| MedlinePlus = a602016
| DailyMedID = Modafinil
| pregnancy_AU = D
| pregnancy_AU_comment = <ref name="Modavigil PI" />
| pregnancy_category = 
| dependency_liability = Relatively low<ref name="modafinil-schedule-IV-1999"/>
| addiction_liability = Low<ref name="modafinil-schedule-IV-1999"/>
| routes_of_administration = [[Oral administration|By mouth]]<ref name="Drugs.com-Monograph-2023"/>
| class = {{plainlist|
* [[Stimulant]];
* [[Dopamine reuptake inhibitor]];
* [[Wakefulness-promoting agent]]}}
| ATC_prefix = N06
| ATC_suffix = BA07
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="Modavigil PI">{{cite web | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-01898-1 | title=TGA eBS - Product and Consumer Medicine Information Licence | access-date=February 28, 2024 }}</ref>
| legal_BR = B1
| legal_BR_comment = <ref name="Diario Oficial da Uniao-2023">{{cite web |author-link=Brazilian Health Regulatory Agency |date=March 31, 2023 |title=RDC Nº 784 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=August 3, 2023 |access-date=August 3, 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=April 4, 2023}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = <ref name="Modafinil Product information">{{cite web | title=Modafinil Product information | website=Health Canada | date=April 25, 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=63139 | access-date=June 10, 2022 | archive-date=June 10, 2022 | archive-url=https://web.archive.org/web/20220610220622/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=63139 | url-status=live }}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = <ref name="Modafinil Provigil SmPC">{{cite web | url=https://www.medicines.org.uk/emc/product/5412/smpc | title=Modafinil Provigil 100 mg Tablets – Summary of Product Characteristics (SMPC) – (Emc) | website=emc | date=June 9, 2021 | access-date=December 1, 2023 | archive-date=December 2, 2023 | archive-url=https://web.archive.org/web/20231202185852/https://www.medicines.org.uk/emc/product/5412/smpc | url-status=live }}</ref>
| legal_US = Schedule IV
| legal_US_comment = <ref name="modafinil-schedule-IV-1999"/><ref name="Provigil FDA label">{{cite web | title=Provigil- modafinil tablet | work = DailyMed | date=November 30, 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e16c26ad-7bc2-d155-3a5d-da83ad6492c8 | access-date=June 10, 2022 | archive-date=June 10, 2022 | archive-url=https://web.archive.org/web/20220610220626/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e16c26ad-7bc2-d155-3a5d-da83ad6492c8 | url-status=live }}</ref>
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- Pharmacokinetic data -->
| bioavailability = 40–65% (based on [[urine|urinary]] [[excretion]])<ref name="SousaDinis-Oliveira2020">{{cite journal | vauthors = Sousa A, Dinis-Oliveira RJ | title = Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects | journal = Subst Abus | volume = 41 | issue = 2 | pages = 155–173 | date = 2020 | pmid = 31951804 | doi = 10.1080/08897077.2019.1700584 | bibcode = 2020JPkR...41..155S | url = }}</ref><ref name="HerseyTanda2024">{{cite book | vauthors = Hersey M, Tanda G | title = Pharmacological Advances in Central Nervous System Stimulants | chapter = Modafinil, an atypical CNS stimulant? | series = Adv Pharmacol | volume = 99 | pages = 287–326 | date = 2024 | pmid = 38467484 | doi = 10.1016/bs.apha.2023.10.006 | pmc = 12004278 | isbn = 978-0-443-21933-7 | chapter-url = }}</ref>
| protein_bound = ~60% (mainly to [[human serum albumin|albumin]])<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| metabolism = [[Liver]] ([[amide]] [[hydrolysis]], ''S''-[[oxidation]], [[aromatic ring]] [[hydroxylation]], [[glucuronidation|glucuronide]] [[conjugation (biochemistry)|conjugation]]; [[CYP1A2]], [[CYP2B6]], [[CYP2C9]], [[CYP2C19]], [[CYP3A4]], [[CYP3A5]] involved)<ref name="SousaDinis-Oliveira2020" /><ref name="pmid12537513"/><ref name="pmid10820139">{{cite journal | vauthors = Robertson P, DeCory HH, Madan A, Parkinson A | title = In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil | journal = Drug Metabolism and Disposition | volume = 28 | issue = 6 | pages = 664–671 | date = June 2000 | doi = 10.1016/S0090-9556(24)15146-X | pmid = 10820139 }}</ref>
| metabolites = • [[Modafinil acid]] (35–65%)<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" /><br />• [[Modafinil sulfone]]<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| onset = 2–4{{nbsp}}hours ([[Tmax (pharmacology)|peak]])<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| elimination_half-life = Modafinil: {{Val|12|-|15|u=hour}}<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" /><ref name="pmid12537513">{{cite journal | vauthors = Robertson P, Hellriegel ET | title = Clinical pharmacokinetic profile of modafinil | journal = Clinical Pharmacokinetics | volume = 42 | issue = 2 | pages = 123–137 | date = 2003 | pmid = 12537513 | doi = 10.2165/00003088-200342020-00002 | s2cid = 1266677 }}</ref><br />[[Armodafinil]]: 10–17{{nbsp}}h<ref name="NiemegeersMaudensMorrens2012">{{cite journal | vauthors = Niemegeers P, Maudens KE, Morrens M, Patteet L, Joos L, Neels H, Sabbe BG | title = Pharmacokinetic evaluation of armodafinil for the treatment of bipolar depression | journal = Expert Opin Drug Metab Toxicol | volume = 8 | issue = 9 | pages = 1189–1197 | date = September 2012 | pmid = 22803602 | doi = 10.1517/17425255.2012.708338 | url = }}</ref><ref name="HerseyTanda2024" /><br />[[Esmodafinil]]: 3–5{{nbsp}}h<ref name="SousaDinis-Oliveira2020" /><ref name="HerseyTanda2024" />
| duration_of_action = {{Val|11.5|u=hour}}<ref name="pmid22375280"/>
| excretion = [[Urine]]: 80% (≤10% as modafinil, 35–51% as modafinil acid)<ref name="NiemegeersMaudensMorrens2012" /><ref name="HerseyTanda2024" /><br />[[Feces]]: 1.0%<ref name="NiemegeersMaudensMorrens2012" />

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 68693-11-8
| CAS_supplemental = 
| PubChem = 4236
| IUPHAR_ligand = 7555
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4088
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = R3UK8X3U3D
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01832
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 31859
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1373
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = CRL-40476; CRC-40476; CEP-1538; DEP-1538; Diphenylmethyl-sulfinylacetamide

<!-- Chemical data -->| IUPAC_name = 2-(diphenylmethanesulfinyl)acetamide
| C = 15
| H = 15
| N = 1
| O = 2
| S = 1
| SMILES = O=S(C(c1ccccc1)c2ccccc2)CC(=O)N
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H15NO2S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H2,16,17)
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YFGHCGITMMYXAQ-UHFFFAOYSA-N

<!-- Physical data -->| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

'''Modafinil''', sold under the brand name '''Provigil''' among others, is a [[central nervous system]] (CNS) [[stimulant]] and [[wakefulness-promoting agent|eugeroic]] ([[wakefulness]] promoter) medication used primarily to treat [[narcolepsy]],<ref name="Drugs.com-Monograph-2023">{{cite web |title=Modafinil Monograph for Professionals |url=https://www.drugs.com/monograph/modafinil.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |date=September 23, 2023 |access-date=February 3, 2024 |archive-date=March 30, 2019 |archive-url=https://web.archive.org/web/20190330181813/https://www.drugs.com/monograph/modafinil.html |url-status=live }}</ref><ref name="Provigil FDA label" /><ref name="medlineplus.gov-modafinil">{{cite web|url=https://medlineplus.gov/druginfo/meds/a602016.html|website=MedlinePlus|date=February 15, 2016|title=Modafinil|access-date=February 3, 2024|publisher=US National Library of Medicine|archive-date=December 7, 2023|archive-url=https://web.archive.org/web/20231207203943/https://medlineplus.gov/druginfo/meds/a602016.html|url-status=live}}</ref> a [[sleep disorder]] characterized by [[excessive daytime sleepiness]] and sudden [[Microsleep|sleep attacks]].<ref name="pmid34743789"/> Modafinil is also approved for stimulating wakefulness in people with [[sleep apnea]] and [[shift work sleep disorder]].<ref name="Drugs.com-Monograph-2023"/> It is taken [[by mouth]].<ref name="Drugs.com-Monograph-2023"/><ref name="Provigil FDA label" /> Modafinil is not approved by the US [[Food and Drug Administration]] (FDA) for use in people under 18 years old.<ref name="Provigil FDA label" />

<!-- Contraindications -->
Common side effects of modafinil include [[anxiety]], [[insomnia]], [[dizziness]], and [[headache]]. Modafinil has potential for causing severe [[allergic reaction]]s, [[Psychiatry|psychiatric]] effects,<ref name="Drugs.com-Monograph-2023" /> [[hypersensitivity]], [[adverse effect|adverse]] [[drug interaction|interactions]] with [[prescription drug]]s, and misuse or [[drug abuse|abuse]].<ref name="Drugs.com-Monograph-2023"/><ref name="Provigil FDA label" /><ref name="medlineplus.gov-modafinil"/> Modafinil may harm the [[fetus]] if taken during or two months prior to [[pregnancy]].<ref name="pmid33074297">{{cite journal |vauthors=Kaplan S, Braverman DL, Frishman I, Bartov N |title=Pregnancy and Fetal Outcomes Following Exposure to Modafinil and Armodafinil During Pregnancy |journal=JAMA Internal Medicine |volume=181 |issue=2 |pages=275–277 |date=February 2021 |pmid=33074297 |pmc=7573789 |doi=10.1001/jamainternmed.2020.4009 }}</ref>

<!-- Use in non-sleep-deprived individuals -->
While modafinil is used as a [[Nootropic|cognitive enhancer]], or "smart drug", among healthy individuals seeking improved focus and productivity,<ref name="economist-2008-05-22"/><ref name="Slotnik-2017"/> its use outside medical supervision raises concerns regarding potential misuse or abuse.<ref name="Drugs.com-Monograph-2023" /><ref name="Provigil FDA label"/><ref name="pmid30285371">{{cite book |title=StatPearls |vauthors=Greenblatt K, Adams N |date=February 2022 |publisher=StatPearls Publishing |location=Treasure Island (FL) |chapter=Modafinil |pmid=30285371 |id={{NCBIBook|NBK531476}}}}</ref> Research on the cognitive enhancement effects of modafinil in non-sleep deprived individuals has yielded mixed results, with some studies suggesting modest improvements in attention and [[executive functions]], while others show no significant benefits or a decline in cognitive functions at high doses.<ref name="pmid36056861"/><ref name="pmid32341841"/>
{{TOC limit}}

==Uses==
===Medical===
====Sleep disorders====
{{See also|Sleep disorder}}
Modafinil, a [[eugeroic]] or [[wakefulness-promoting drug]], is primarily used for treating narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks.<ref name="pmid34743789">{{cite journal | vauthors = Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD, Watson NF | title = Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline | journal = Journal of Clinical Sleep Medicine | volume = 17 | issue = 9 | pages = 1881–1893 | date = September 2021 | pmid = 34743789 | pmc = 8636351 | doi = 10.5664/jcsm.9328 }}</ref> Being a [[central nervous system]] (CNS) [[stimulant]] itself,<ref name="pmid38725665">{{cite journal |vauthors=Cid-Jofré V, Bahamondes T, Zúñiga Correa A, Ahumada Arias I, Reyes-Parada M, Renard GM |title=Psychostimulants and social behaviors |journal=Front Pharmacol |volume=15 |article-number=1364630 |date=2024 |pmid=38725665 |pmc=11079219 |doi=10.3389/fphar.2024.1364630|doi-access=free }}</ref> modafinil has lower addictive potential than classical stimulants such as [[amphetamine]], [[cocaine]], or [[methylphenidate]],<ref name="pmid22375280">{{cite journal | vauthors = Kim D | title = Practical use and risk of modafinil, a novel waking drug | journal = Environmental Health and Toxicology | volume = 27 | article-number = e2012007 | date = 2012 | pmid = 22375280 | pmc = 3286657 | doi = 10.5620/eht.2012.27.e2012007 }}</ref><ref name="pmid32927246">{{cite journal | vauthors = Tanda G, Hersey M, Hempel B, Xi ZX, Newman AH | title = Modafinil and its structural analogs as atypical dopamine uptake inhibitors and potential medications for psychostimulant use disorder | journal = Current Opinion in Pharmacology | volume = 56 | pages = 13–21 | date = February 2021 | pmid = 32927246 | pmc = 8247144 | doi = 10.1016/j.coph.2020.07.007 }}</ref><ref name="pmid33435717">{{cite journal |vauthors= Kakehi S, Tompkins DM |title=A Review of Pharmacologic Neurostimulant Use During Rehabilitation and Recovery After Brain Injury |journal=Ann Pharmacother |volume=55 |issue=10 |pages=1254–1266 |date=October 2021 |pmid=33435717 |doi=10.1177/1060028020983607 |s2cid=231593912 }}</ref> but still produces [[Psychoactive drug|psychoactive]] and subjective effects typical of classical stimulants.<ref name="Drugs.com-Monograph-2023" /><ref name="Provigil FDA label"/><ref name="pmid30285371"/>

Narcolepsy causes a strong urge to sleep during the day and can include symptoms like [[cataplexy]] (sudden muscle weakness), [[sleep paralysis]] (inability to move or speak while falling asleep or waking up), and [[hallucination]]s. Narcolepsy is linked to a lack of the brain chemical [[hypocretin]] ([[orexin]]), primarily produced in the [[hypothalamus]].<ref name="pmid35624073">{{cite journal | vauthors = Barateau L, Pizza F, Plazzi G, Dauvilliers Y | title = Narcolepsy | journal = Journal of Sleep Research | volume = 31 | issue = 4 | article-number = e13631 | date = August 2022 | pmid = 35624073 | doi = 10.1111/jsr.13631 | s2cid = 251107306 | hdl = 11380/1280615 | hdl-access = free }}</ref><ref name="pmid34031309">{{cite journal | vauthors = Anderson D | title = Narcolepsy: A clinical review | journal = JAAPA | volume = 34 | issue = 6 | pages = 20–25 | date = June 2021 | pmid = 34031309 | doi = 10.1097/01.JAA.0000750944.46705.36 | s2cid = 241205299 | doi-access = free | title-link = doi }}</ref> Modafinil is not a cure for narcolepsy, but it can help manage the symptoms. While modafinil is primarily used to treat excessive sleepiness, it may also help reduce the frequency and severity of cataplexy attacks in some people. Modafinil is approved for management of narcolepsy with or without cataplexy. However, it is not specifically approved for the treatment of cataplexy.<ref name="govuk-Modafinil Now restricted to narcolepsy"/><ref name="pmid28443381">{{cite journal |vauthors=Kallweit U, Bassetti CL |title=Pharmacological management of narcolepsy with and without cataplexy |journal=Expert Opin Pharmacother |volume=18 |issue=8 |pages=809–817 |date=June 2017 |pmid=28443381 |doi=10.1080/14656566.2017.1323877 |s2cid=1906751 }}</ref>

Modafinil is also prescribed for [[shift work sleep disorder]].<ref name="Provigil FDA label" />

Modafinil performs moderately (but better than [[armodafinil]] or [[solriamfetol]])<ref name="pmid39243682">{{cite journal |vauthors=Wang Y, Zhang W, Ye H, Xiao Y |title=Excessive daytime sleepiness in obstructive sleep apnea: Indirect treatment comparison of wake-promoting agents in patients adherent/nonadherent to primary OSA therapy |journal=Sleep Med Rev |volume=78 |issue= |article-number=101997 |date=August 2024 |pmid=39243682 |doi=10.1016/j.smrv.2024.101997 |url=|doi-access=free }}</ref> as a drug to overcome [[excessive daytime sleepiness]] caused by [[obstructive sleep apnea]],<ref name="pmid38754208">{{cite journal |vauthors=Neshat SS, Heidari A, Henriquez-Beltran M, Patel K, Colaco B, Arunthari V, Lee Mateus AY, Cheung J, Labarca G |title=Evaluating pharmacological treatments for excessive daytime sleepiness in obstructive sleep apnea: A comprehensive network meta-analysis and systematic review |journal=Sleep Med Rev |volume=76 |issue= |article-number=101934 |date=August 2024 |pmid=38754208 |doi=10.1016/j.smrv.2024.101934}}</ref> though it is recommended that people with apnea use [[continuous positive airway pressure]] (CPAP) therapy, that is a sleep breathing apparatus to prevent apnea, before starting modafinil.<ref name="Provigil FDA label" /><ref name="pmid32341841">{{cite journal | vauthors = Hashemian SM, Farhadi T | title = A review on modafinil: the characteristics, function, and use in critical care | journal = Journal of Drug Assessment | volume = 9 | issue = 1 | pages = 82–86 | date = 2020 | pmid = 32341841 | pmc = 7170336 | doi = 10.1080/21556660.2020.1745209 }}</ref><ref name="pmid18041479">{{cite journal | vauthors = Morgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B, Brown T, Chesson AL, Kapur V, Maganti R, Owens J, Pancer J, Swick TJ, Zak R | title = Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report | journal = Sleep | volume = 30 | issue = 11 | pages = 1445–1459 | date = November 2007 | pmid = 18041479 | pmc = 2082098 | doi = 10.1093/sleep/30.11.1445 }}</ref> When obstructive sleep apnea is comorbid with narcolepsy, modafinil is an effective drug to reduce the associated excessive daytime sleepiness.<ref name="pmid39386319">{{cite journal |vauthors=Miano S, Kheirandish-Gozal L, De Pieri M |title=Comorbidity of obstructive sleep apnea and narcolepsy: A challenging diagnosis and complex management |journal=Sleep Med X |volume=8 |issue= |article-number=100126 |date=December 2024 |pmid=39386319 |doi=10.1016/j.sleepx.2024.100126|pmc=11462365 }}</ref>

Modafinil's use varies by region. In the US, it is approved for adult narcolepsy, shift work sleep disorder, and obstructive sleep apnea, but not for children.<ref name="pmid30285371"/> In the UK and the EU, since 2014, it is approved solely for narcolepsy, including in children ([[pediatric narcolepsy]]), with its use for other conditions restricted by the European Medicines Agency.<ref name="govuk-Modafinil Now restricted to narcolepsy">{{cite web | url=https://www.gov.uk/drug-safety-update/modafinil-provigil-now-restricted-to-narcolepsy | title=Modafinil (Provigil): Now restricted to narcolepsy | work=[[Medicines and Healthcare products Regulatory Agency]] | access-date=December 2, 2023 | archive-date=December 15, 2023 | archive-url=https://web.archive.org/web/20231215212604/https://www.gov.uk/drug-safety-update/modafinil-provigil-now-restricted-to-narcolepsy | url-status=live }}</ref><ref name="Modafinil: Restricted use recommended">{{cite web | url=https://www.gov.uk/drug-safety-update/modafinil-restricted-use-recommended | title=Modafinil: Restricted use recommended | publisher=[[Medicines and Healthcare products Regulatory Agency]] | access-date=December 2, 2023 | archive-date=December 2, 2023 | archive-url=https://web.archive.org/web/20231202141511/https://www.gov.uk/drug-safety-update/modafinil-restricted-use-recommended | url-status=live }}</ref>

{{As of|2024|post=,}} both the French and the American Academy of Sleep Medicine strongly recommend modafinil as the first-choice treatment for narcolepsy.<ref name="pmid36921459">{{cite journal | vauthors = Arnulf I, Thomas R, Roy A, Dauvilliers Y | title = Update on the treatment of idiopathic hypersomnia: Progress, challenges, and expert opinion | journal = Sleep Medicine Reviews | volume = 69 | article-number = 101766 | date = June 2023 | pmid = 36921459 | doi = 10.1016/j.smrv.2023.101766 | s2cid = 257214950 | doi-access = free | title-link = doi | url = https://hal.science/hal-04588723/document | access-date = July 13, 2024 | archive-date = August 6, 2024 | archive-url = https://web.archive.org/web/20240806000406/https://hal.science/hal-04588723/document | url-status = live }}</ref> In Europe, modafinil is considered one of the primary drugs recommended for treating narcolepsy according to the guidelines.<ref name="pmid37839272">{{cite journal |vauthors=Winter Y, Lang C, Kallweit U, Apel D, Fleischer V, Ellwardt E, Groppa S |title=Pitolisant-supported bridging during drug holidays to deal with tolerance to modafinil in patients with narcolepsy |journal=Sleep Med |volume=112 |pages=116–121 |date=December 2023 |pmid=37839272 |doi=10.1016/j.sleep.2023.10.005 |doi-access=free }}</ref>

====Multiple sclerosis-related fatigue====
Fatigue is a common and often debilitating symptom experienced by people with MS.<ref name="pmid35572947">{{cite journal |vauthors=Ayache SS, Serratrice N, Abi Lahoud GN, Chalah MA |title=Fatigue in Multiple Sclerosis: A Review of the Exploratory and Therapeutic Potential of Non-Invasive Brain Stimulation |journal=Frontiers in Neurology |volume=13 |article-number=813965 |date=2022 |pmid=35572947 |pmc=9101483 |doi=10.3389/fneur.2022.813965 |doi-access=free }}</ref><ref name="pmid34856949">{{cite journal |vauthors=Oliva Ramirez A, Keenan A, Kalau O, Worthington E, Cohen L, Singh S |title=Prevalence and burden of multiple sclerosis-related fatigue: a systematic literature review |journal=BMC Neurology |volume=21 |issue=1 |article-number=468 |date=December 2021 |pmid=34856949 |pmc=8638268 |doi=10.1186/s12883-021-02396-1 |doi-access=free }}</ref>

When modafinil is prescribed for fatigue, some people with MS may experience increased energy levels, reduced feelings of tiredness, improved cognitive function, and better quality of life.<ref name="pmid38988104">{{cite journal |vauthors=Ghazanfar S, Farooq M, Qazi SU, Chaurasia B, Kaunzner U |title=The use of modafinil for the treatment of fatigue in multiple sclerosis: A systematic review and meta-analysis of controlled clinical trials |journal=Brain and Behavior |volume=14 |issue=7 |article-number=e3623 |date=July 2024 |pmid=38988104 |pmc=11237168 |doi=10.1002/brb3.3623 }}</ref>{{Failed verification|date=August 2025|talk=Statistical Significance}} Two reviews concluded that modafinil has minor effectiveness in managing fatigue in people with MS,<ref name="pmid38988104"/><ref name="pmid37445551"/> and optimal dosing and treatment schedules are not well established.<ref name="pmid37445551">{{cite journal | vauthors = Ciancio A, Moretti MC, Natale A, Rodolico A, Signorelli MS, Petralia A, Altamura M, Bellomo A, Zanghì A, D'Amico E, Avolio C, Concerto C | title = Personality Traits and Fatigue in Multiple Sclerosis: A Narrative Review | journal = Journal of Clinical Medicine | volume = 12 | issue = 13 | page = 4518 | date = July 2023 | pmid = 37445551 | pmc = 10342558 | doi = 10.3390/jcm12134518 | doi-access = free | title-link = doi }}</ref><ref name="pmid29175676">{{cite journal |vauthors=Shangyan H, Kuiqing L, Yumin X, Jie C, Weixiong L |title=Meta-analysis of the efficacy of modafinil versus placebo in the treatment of multiple sclerosis fatigue |journal=Multiple Sclerosis and Related Disorders |volume=19 |pages=85–89 |date=January 2018 |pmid=29175676 |doi=10.1016/j.msard.2017.10.011}}</ref> Clinical assessments have found that adverse events were common.<ref name=pmid38988104/><ref>{{Cite web |date=2023-09-01 |title=Comparing Treatments for Multiple Sclerosis-Related Fatigue - Evidence Update for Clinicians |url=https://www.pcori.org/evidence-updates/comparing-treatments-multiple-sclerosis-related-fatigue |access-date=2024-11-15 |website=Patient-Centered Outcomes Research Institute |language=en}}</ref> The American [[National Multiple Sclerosis Society]] states that modafinil can be used off-label to alleviate fatigue associated with MS.<ref name="National Multiple Sclerosis Society">{{cite web |url=https://www.nationalmssociety.org/for-professionals/for-healthcare-professionals/managing-and-treating-ms/symptom-management/fatigue-management |title=Fatigue management |publisher=US National Multiple Sclerosis Society|date=2025 |access-date=August 26, 2025}}</ref>

====Attention deficit hyperactivity disorder====
{{See also|Attention deficit hyperactivity disorder}}
Modafinil is occasionally prescribed [[off-label]] for individuals with attention deficit hyperactivity disorder (ADHD).<ref name="pmid31200137">{{cite journal | vauthors = Wilms W, Woźniak-Karczewska M, Corvini PF, Chrzanowski Ł | title = Nootropic drugs: Methylphenidate, modafinil and piracetam - Population use trends, occurrence in the environment, ecotoxicity and removal methods - A review | journal = Chemosphere | volume = 233 | pages = 771–785 | date = October 2019 | pmid = 31200137 | doi = 10.1016/j.chemosphere.2019.06.016 | s2cid = 189861826 | bibcode = 2019Chmsp.233..771W }}</ref><ref name="pmid33516734">{{cite journal | vauthors = Kittel-Schneider S, Quednow BB, Leutritz AL, McNeill RV, Reif A | title = Parental ADHD in pregnancy and the postpartum period - A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 124 | pages = 63–77 | date = May 2021 | pmid = 33516734 | doi = 10.1016/j.neubiorev.2021.01.002 | s2cid = 231723198 | url = https://www.zora.uzh.ch/id/eprint/198979/1/Kittel-Schneider_et_al_2021.pdf | access-date = October 19, 2023 | archive-date = October 21, 2023 | archive-url = https://web.archive.org/web/20231021234946/https://www.zora.uzh.ch/id/eprint/198979/1/Kittel-Schneider_et_al_2021.pdf | url-status = live }}</ref><ref name="pmid29952165">{{cite journal | vauthors = Weiergräber M, Ehninger D, Broich K | title = Neuroenhancement and mood enhancement – Physiological and pharmacodynamical background | journal = Medizinische Monatsschrift für Pharmazeuten | volume = 40 | issue = 4 | pages = 154–164 | date = April 2017 | pmid = 29952165 }}</ref> It has not consistently shown efficacy in treating adult ADHD,<ref name="pmid38433530">{{cite journal |vauthors=Miskowiak KW, Obel ZK, Guglielmo R, Bonnin CD, Bowie CR, Balanzá-Martínez V, Burdick KE, Carvalho AF, Dols A, Douglas K, Gallagher P, Kessing LV, Lafer B, Lewandowski KE, López-Jaramillo C, Martinez-Aran A, McIntyre RS, Porter RJ, Purdon SE, Schaffer A, Stokes PR, Sumiyoshi T, Torres IJ, Van Rheenen TE, Yatham LN, Young AH, Vieta E, Hasler G |title=Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force |journal=Bipolar Disord |volume=26 |issue=3 |pages=216–239 |date=May 2024 |pmid=38433530 |doi=10.1111/bdi.13414|url=https://eprints.ncl.ac.uk/file_store/production/297410/28FECDCD-DACE-49B2-8260-46BED7B5094C.pdf }}</ref> especially when compared to other treatments such as [[lisdexamfetamine]].<ref name="pmid30117329">{{cite journal | vauthors = Stuhec M, Lukić P, Locatelli I | title = Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis | journal = The Annals of Pharmacotherapy | volume = 53 | issue = 2 | pages = 121–133 | date = February 2019 | pmid = 30117329 | doi = 10.1177/1060028018795703 | s2cid = 52019992 }}</ref><ref name="pmid26693882" /> In children, modafinil is more effective than placebo for treating ADHD symptoms.<ref name="pmid30097390">{{cite journal | vauthors = Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, Atkinson LZ, Tessari L, Banaschewski T, Coghill D, Hollis C, Simonoff E, Zuddas A, Barbui C, Purgato M, Steinhausen HC, Shokraneh F, Xia J, Cipriani A | title = Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis | journal = The Lancet. Psychiatry | volume = 5 | issue = 9 | pages = 727–738 | date = September 2018 | pmid = 30097390 | pmc = 6109107 | doi = 10.1016/S2215-0366(18)30269-4 }}</ref><ref name="pmid32845025">{{cite journal | vauthors = Rodrigues R, Lai MC, Beswick A, Gorman DA, Anagnostou E, Szatmari P, Anderson KK, Ameis SH | title = Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis | journal = Journal of Child Psychology and Psychiatry, and Allied Disciplines | volume = 62 | issue = 6 | pages = 680–700 | date = June 2021 | pmid = 32845025 | doi = 10.1111/jcpp.13305 | s2cid = 221329069 }}</ref>

Given its approved status in the US to treat narcolepsy, physicians can also prescribe modafinil for off-label uses, such as treating ADHD in both children and adults.<ref name="pmid16669720" /><ref name="pmid16623645">{{cite journal | vauthors = Turner D | title = A review of the use of modafinil for attention-deficit hyperactivity disorder | journal = Expert Review of Neurotherapeutics | volume = 6 | issue = 4 | pages = 455–468 | date = April 2006 | pmid = 16623645 | doi = 10.1586/14737175.6.4.455 | s2cid = 24293088 }}</ref><ref name="pmid16954326">{{cite journal | vauthors = Lindsay SE, Gudelsky GA, Heaton PC | title = Use of modafinil for the treatment of attention deficit/hyperactivity disorder | journal = The Annals of Pharmacotherapy | volume = 40 | issue = 10 | pages = 1829–1833 | date = October 2006 | pmid = 16954326 | doi = 10.1345/aph.1H024 | s2cid = 37368284 }}</ref>

The Canadian Network for Mood and Anxiety Treatments (CANMAT) suggests modafinil as a second-line treament for comorbid ADHD and [[bipolar disorder]], after first-line [[Management of attention deficit hyperactivity disorder#Stimulants|psychostimulants]] and the antidepressant [[bupropion]].<ref name="pmid22303520">{{cite journal | vauthors = Bond DJ, Hadjipavlou G, Lam RW, McIntyre RS, Beaulieu S, Schaffer A, Weiss M | title = The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder | journal = Annals of Clinical Psychiatry | volume = 24 | issue = 1 | pages = 23–37 | date = February 2012 | doi = 10.1177/104012371202400104 | pmid = 22303520 }}</ref>

====Bipolar disorder====
{{See also|Bipolar disorder}}
Modafinil is used off-label as an [[adjunctive treatment]] (i.e., in combination therapy) for the acute depressive phase in bipolar disorder.<ref name=retz-2022>{{cite book|chapter=Efficacy of Amphetamines, Methylphenidate, and Modafinil in the Treatment of Mental Disorders|doi=10.1007/978-3-030-62059-2_319|vauthors=Retz W|title=NeuroPsychopharmacotherapy |date=2022 |pages=2465–2486 |isbn=978-3-030-62058-5 }}</ref><ref name="pmid22717304">{{cite journal |vauthors=Dell'Osso B, Ketter TA |title=Use of adjunctive stimulants in adult bipolar depression |journal=Int J Neuropsychopharmacol |volume=16 |issue=1 |pages=55–68 |date=February 2013 |pmid=22717304 |doi=10.1017/S1461145712000326 |hdl=2434/265768 |hdl-access=free }}</ref><ref name="pmid28144880"/><ref name="pmid30069121">{{cite journal |vauthors=Shen YC |title=Treatment of acute bipolar depression |journal=Ci Ji Yi Xue Za Zhi |volume=30 |issue=3 |pages=141–147 |date=2018 |pmid=30069121 |pmc=6047324 |doi=10.4103/tcmj.tcmj_71_18 |doi-access=free }}</ref> The depressive phase of [[bipolar disorder]] may feature excessive sleepiness and fatigue. Adjunctive treatment with modafinil can be used as an augmentation for the main treatment to increase its effect and is safe and effective, especially for people who do not respond well to standard antidepressants.<ref name="pmid31643130">{{cite journal | vauthors = Nunez NA, Singh B, Romo-Nava F, Joseph B, Veldic M, Cuellar-Barboza A, Cabello Arreola A, Vande Voort JL, Croarkin P, Moore KM, Biernacka J, McElroy SL, Frye MA | title = Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta-analysis of randomized controlled trials | journal = Bipolar Disorders | volume = 22 | issue = 2 | pages = 109–120 | date = March 2020 | pmid = 31643130 | doi = 10.1111/bdi.12859 | doi-access = free | title-link = doi }}</ref><ref name="pmid36561896">{{cite journal | vauthors = Elsayed OH, Ercis M, Pahwa M, Singh B | title = Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions | journal = Neuropsychiatric Disease and Treatment | volume = 18 | pages = 2927–2943 | date = 2022 | pmid = 36561896 | pmc = 9767030 | doi = 10.2147/NDT.S273503 | doi-access = free | title-link = doi }}</ref><ref name="pmid38433530"/> Modafinil does not significantly increase the risk of mood switch to mania or suicide attempts in people with bipolar disorder.<ref name="r2">{{cite web | url=https://www.proquest.com/openview/017f800499b0259521ea4ef8ccf503a8/1?pq-origsite=gscholar&cbl=5540454 | title=Modafinil in the treatment of selected mental disorders | website=[[ProQuest]] | access-date=February 14, 2024 | archive-date=February 14, 2024 | archive-url=https://web.archive.org/web/20240214153327/https://www.proquest.com/openview/017f800499b0259521ea4ef8ccf503a8/1?pq-origsite=gscholar&cbl=5540454 | url-status=live }}</ref><ref name="pmid31643130"/> Modafinil may also have cognitive benefits in people with bipolar disorder who are in a remission state.<ref name="pmid31951804">{{cite journal |vauthors=Sousa A, Dinis-Oliveira RJ |date=2020 |title=Article commentary: Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects |journal=Substance Abuse |volume=41 |issue=2 |pages=155–173 |doi=10.1080/08897077.2019.1700584 |pmid=31951804 |bibcode=2020JPkR...41..155S |s2cid=210709160}}</ref><ref name="r4">{{cite journal | doi=10.4088/JCP.19r12767 | title=The Potential Procognitive Effects of Modafinil in Major Depressive Disorder | date=2019 | journal=The Journal of Clinical Psychiatry | volume=80 | issue=6 | pmid=31599501 | s2cid=204028869 | vauthors=Vaccarino SR, McInerney SJ, Kennedy SH, Bhat V }}</ref><ref name="pmid38433530"/>

Whereas modafinil and armodafinil are approved for narcolepsy, they have been repurposed as [[adjunct therapy|adjunctive treatments]] to alleviate symptoms of acute depressive phase in people with bipolar disorder.<ref name="pmid34509090">{{cite journal | vauthors = Bartoli F, Cavaleri D, Bachi B, Moretti F, Riboldi I, Crocamo C, Carrà G | title = Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials | journal = Journal of Psychiatric Research | volume = 143 | pages = 230–238 | date = November 2021 | pmid = 34509090 | doi = 10.1016/j.jpsychires.2021.09.018 | s2cid = 237485915 }}</ref> Drug repurposing in psychiatry is a strategy for discovering new uses for drugs that have already been approved or tested in clinical trials for other illnesses. As such, drug repurposing is a rapid, cost-effective, and reduced-risk strategy for the development of new treatment options for psychiatric disorders.<ref name="pmid34509090"/> 2021 [[meta-analysis]] concluded that add-on modafinil and armodafinil were more effective than placebo on response to treatment, clinical remission, and reduction in depressive symptoms, with only minor side effects, but the effect sizes are small and the quality of evidence is therefore low, limiting the clinical relevance of the evidence.<ref name="pmid34509090"/><ref name="r6">{{cite journal | doi=10.1080/14656566.2023.2194488 | title=An update on potential pharmacotherapies for cognitive impairment in bipolar disorder | date=2023 | journal=Expert Opinion on Pharmacotherapy | volume=24 | issue=5 | pages=641–654 | pmid=36946229 | s2cid=257665446 | vauthors=Johnson DE, McIntyre RS, Mansur RB, Rosenblat JD }}</ref> Very low rates of mood swing (a change in mood from one extreme to another)<ref name="r2"/><ref name="pmid20492846">{{cite journal | vauthors = Salvadore G, Quiroz JA, Machado-Vieira R, Henter ID, Manji HK, Zarate CA | title = The neurobiology of the switch process in bipolar disorder: a review | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 11 | pages = 1488–1501 | date = November 2010 | pmid = 20492846 | pmc = 3000635 | doi = 10.4088/JCP.09r05259gre }}</ref> have been observed with modafinil and armodafinil in depressive phase of bipolar disorder.<ref name="pmid28144880">{{cite journal | vauthors = Perugi G, Vannucchi G, Bedani F, Favaretto E | title = Use of Stimulants in Bipolar Disorder | journal = Current Psychiatry Reports | volume = 19 | issue = 1 | article-number = 7 | date = January 2017 | pmid = 28144880 | doi = 10.1007/s11920-017-0758-x | s2cid = 2932701 }}</ref><ref name="pmid25295426" />

===Occupational===
{{See also|List of psychoactive drugs used by militaries}}

Modafinil was used during the [[Gulf War]] by the [[French Foreign Legion]],<ref name="pmid30174215" /> the [[United States Air Force|US Air Force]],<ref name="pmid34632515">{{cite journal | vauthors = Van Puyvelde M, Van Cutsem J, Lacroix E, Pattyn N | title = A State-of-the-Art Review on the Use of Modafinil as a Performance-enhancing Drug in the Context of Military Operationality | journal = Military Medicine | volume = 187 | issue = 1–2 | pages = 52–64 | date = January 2022 | pmid = 34632515 | doi = 10.1093/milmed/usab398 | doi-access = free | title-link = doi }}</ref><ref name="Brunye-2020">{{cite journal|vauthors=Brunyé TT, Brou R, Doty TJ|title=A Review of US Army Research Contributing to Cognitive Enhancement in Military Contexts|journal=J Cogn Enhanc|volume=4 |issue= 4|pages=453–468|year=2020|doi=10.1007/s41465-020-00167-3|s2cid=256621326 }}</ref> and [[United States Marine Corps|US Marines]]<ref name="Go Pills for Black Shoes?">{{cite journal | vauthors = Gonzalez J | url = https://www.usni.org/magazines/proceedings/2017/july/go-pills-black-shoes | title = Go Pills for Black Shoes? | journal = U.S. Naval Institute Proceedings | date = July 2017 | volume = 143 | issue = 7/1,373 | access-date = December 3, 2023 | archive-date = December 3, 2023 | archive-url = https://web.archive.org/web/20231203140637/https://www.usni.org/magazines/proceedings/2017/july/go-pills-black-shoes | url-status = live }}</ref> to enhance "operational tempo" (a term that denotes the speed and intensity at which military operations or activities are executed), aiming to optimize the overall performance and efficiency of the units.<ref name="Brunye-2020" /><ref name="pmid16018329">{{cite journal | vauthors = Caldwell JA, Caldwell JL | title = Fatigue in military aviation: an overview of US military-approved pharmacological countermeasures | journal = Aviation, Space, and Environmental Medicine | volume = 76 | issue = 7 Suppl | pages = C39–C51 | date = July 2005 | pmid = 16018329 }}</ref><ref name="guardian2004">{{cite news | url=https://www.theguardian.com/society/2004/jul/29/health.sciencenews | title=MoD bought thousands of stay awake pills in advance of war in Iraq | newspaper=[[The Guardian]] | date=July 29, 2004 | vauthors=Sample I, Evans R | access-date=December 2, 2023 | archive-date=December 2, 2023 | archive-url=https://web.archive.org/web/20231202042216/https://www.theguardian.com/society/2004/jul/29/health.sciencenews | url-status=live }}</ref>

Armed forces in various countries, including the United States, the United Kingdom, India, and France, have considered modafinil as an alternative to traditional [[Substituted amphetamine|amphetamines]] for managing sleep deprivation in combat or extended missions.<ref name="Martin-2003">{{cite magazine|url=https://www.wired.com/2003/11/sleep/|title=It's Wake-Up Time|vauthors=Martin R|date=November 1, 2003|magazine=Wired|access-date=May 23, 2019|issn=1059-1028|archive-date=October 17, 2020|archive-url=https://web.archive.org/web/20201017212750/https://www.wired.com/2003/11/sleep/|url-status=live}}</ref> The US military approved modafinil for specific Air Force missions, replacing [[Amphetamine|amphetamines]] for fatigue management.<ref name="Air Force Special Operations Command Instruction 48–101-2012">{{cite web | title = Air Force Special Operations Command Instruction 48–101 | archive-url = https://web.archive.org/web/20180410202141/http://static.e-publishing.af.mil/production/1/afsoc/publication/afi11-202v3_afsocsup/afi11-202v3_afsocsup.pdf | archive-date= April 10, 2018 | quote = (sects. 1.7.4), U.S. Air Force Special Operations Command | date = November 30, 2012 | url = http://static.e-publishing.af.mil/production/1/afsoc/publication/afi11-202v3_afsocsup/afi11-202v3_afsocsup.pdf }}</ref> The use of modafinil in military contexts without sleep deprivation is not recommended due to inconclusive evidence on its cognitive enhancement benefits and potential risks of adverse effects.<ref name="pmid34632515" />

Modafinil is also available to astronauts aboard the [[International Space Station]] for the management of fatigue caused by circadian dyssynchrony in orbit.<ref name="pmid19487390">{{cite journal | vauthors = Thirsk R, Kuipers A, Mukai C, Williams D | title = The space-flight environment: the International Space Station and beyond | journal = CMAJ | volume = 180 | issue = 12 | pages = 1216–1220 | date = June 2009 | pmid = 19487390 | pmc = 2691437 | doi = 10.1503/cmaj.081125 }}</ref>

===Non-medical===

Modafinil has been used non-medically as a "smart drug"<ref name="economist-2008-05-22">{{cite news |vauthors=Slotnik DE |title=Smart drugs |newspaper=[[The Economist]] |url=https://www.economist.com/leaders/2008/05/22/smart-drugs |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203141554/https://www.economist.com/leaders/2008/05/22/smart-drugs |url-status=live }}</ref><ref name="Slotnik-2017">{{cite news |vauthors=Slotnik DE |date=October 11, 2017 |title=Michel Jouvet, Who Unlocked REM Sleep's Secrets, Dies at 91 |work=[[The New York Times]] |url=https://www.nytimes.com/2017/10/11/obituaries/michel-jouvet-who-unlocked-rem-sleeps-secrets-dies-at-91.html |access-date=December 3, 2023 |issn=0362-4331 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203143118/https://www.nytimes.com/2017/10/11/obituaries/michel-jouvet-who-unlocked-rem-sleeps-secrets-dies-at-91.html |url-status=live }}</ref> by various groups, including students,<ref name="Cadwalladr-2015">{{cite news|vauthors=Cadwalladr C|title=Students used to take drugs to get high. Now they take them to get higher grades|url=https://www.theguardian.com/society/2015/feb/15/students-smart-drugs-higher-grades-adderall-modafinil|newspaper=[[The Guardian]]|date=February 14, 2015|access-date=January 7, 2017|archive-date=August 3, 2020|archive-url=https://web.archive.org/web/20200803132607/https://www.theguardian.com/society/2015/feb/15/students-smart-drugs-higher-grades-adderall-modafinil|url-status=live}}</ref><ref name="The Economist - The Drug Does Work">{{cite news |vauthors=Cumming E |date=November 3, 2009 |title=The drug does work |newspaper=[[The Economist]] |url=https://www.economist.com/1843/2009/11/03/the-drug-does-work |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203141443/https://www.economist.com/1843/2009/11/03/the-drug-does-work |url-status=live }}</ref><ref name="The Independent-2017">{{cite news|date=May 30, 2017 |title=Professors are taking the same 'smart drugs' as students to keep up with workloads |url=https://www.independent.co.uk/news/education/education-news/professor-smart-drugs-modafinil-noopept-students-workloads-university-research-teaching-academic-cambridge-a7763041.html |access-date=January 17, 2023 |website=The Independent |archive-date=December 7, 2022 |archive-url=https://web.archive.org/web/20221207055128/http://www.independent.co.uk/news/education/education-news/professor-smart-drugs-modafinil-noopept-students-workloads-university-research-teaching-academic-cambridge-a7763041.html |url-status=live }}</ref> office workers, [[transhumanist]]s,<ref name="Talbot - Brain Gain">{{cite magazine|vauthors=Talbot M|title=Brain Gain|url=http://www.newyorker.com/magazine/2009/04/27/brain-gain|magazine=[[The New Yorker]]|access-date=April 9, 2017|archive-date=August 19, 2020|archive-url=https://web.archive.org/web/20200819222934/https://www.newyorker.com/magazine/2009/04/27/brain-gain|url-status=live}}</ref><ref name="The Economist - Toward Immortality">{{cite news |title=Towards immortality |date=November 16, 2006 |newspaper=[[The Economist]] |url=https://www.economist.com/news/2006/11/16/towards-immortality |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203142303/https://www.economist.com/news/2006/11/16/towards-immortality |url-status=live }}</ref> and professionals in various sectors. Its use is attributed by these individuals to its potential for enhancing attention, cognitive capabilities, and [[alertness]].<ref name="pmid34382572">{{cite journal | vauthors = Van Rooyen LR, Gihwala R, Laher AE | title = Stimulant use among prehospital emergency care personnel in Gauteng Province, South Africa | journal = South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde | volume = 111 | issue = 6 | pages = 587–590 | date = May 2021 | pmid = 34382572 | doi = 10.7196/SAMJ.2021.v111i6.15465 | s2cid = 236402826 | doi-access = free | title-link = doi | doi-broken-date = July 1, 2025 }}</ref><ref name="The Economist - Supercharging the brain">{{cite news |title=Supercharging the brain |newspaper=[[The Economist]] |date=September 18, 2004 |url=https://www.economist.com/technology-quarterly/2004/09/18/supercharging-the-brain |access-date=December 3, 2023 |issn=0013-0613 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203143124/https://www.economist.com/technology-quarterly/2004/09/18/supercharging-the-brain |url-status=live }}</ref>

The effectiveness of modafinil as a cognitive enhancer is still debated. Some studies suggest significant increases in cognitive abilities, while others indicate mild to nonexistent cognitive improvements.<ref name="pmid17712350"/><ref name="pmid12417966">{{cite journal | vauthors = Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ | title = Cognitive enhancing effects of modafinil in healthy volunteers | journal = Psychopharmacology | volume = 165 | issue = 3 | pages = 260–269 | date = January 2003 | pmid = 12417966 | doi = 10.1007/s00213-002-1250-8 }}</ref><ref name=retz-2022/><ref name="pmid16142993">{{cite journal |vauthors=Keating GM, Raffin MJ | title=Modafinil: a review of its use in excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder | journal=CNS Drugs | volume=19 |issue=9 |pages=785–803 |date=2005 |pmid=16142993 |doi=10.2165/00023210-200519090-00005 |s2cid=43733424 }}</ref> In some cases, it has even been associated with impairments in certain cognitive functions.<ref name="pmid36056861">{{cite journal | vauthors = Zamanian MY, Karimvandi MN, Nikbakhtzadeh M, Zahedi E, Bokov DO, Kujawska M, Heidari M, Rahmani MR | title = Effects of Modafinil (Provigil) on Memory and Learning in Experimental and Clinical Studies: From Molecular Mechanisms to Behaviour Molecular Mechanisms and Behavioural Effects | journal = Current Molecular Pharmacology | volume = 16 | issue = 4 | pages = 507–516 | date = 2023 | pmid = 36056861 | doi = 10.2174/1874467215666220901122824 | s2cid = 252046371 }}</ref><ref name="pmid32341841" /><ref name="Meulen-2017">{{cite book | vauthors = Meulen R, Hall W, Mohammed A |title=Rethinking Cognitive Enhancement |date=2017 |publisher=Oxford University Press |isbn=978-0-19-872739-2 |page=116 |url=https://books.google.com/books?id=aAIXDgAAQBAJ&pg=PA116 }}</ref> It has been shown that modafinil's positive impact on cognitive abilities is more noticeable on sleep-deprived individuals.<ref name="pmid26381811">{{cite journal | vauthors = Battleday RM, Brem AK | title = Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review | journal = European Neuropsychopharmacology | volume = 25 | issue = 11 | pages = 1865–1881 | date = November 2015 | pmid = 26381811 | doi = 10.1016/j.euroneuro.2015.07.028 | s2cid = 23319688 }}</ref> Therefore, in people who are not sleep-deprived, the potential of modafinil as a cognitive enhancer may be limited.<ref name="pmid35366192">{{cite journal |vauthors=Schifano F, Catalani V, Sharif S, Napoletano F, Corkery JM, Arillotta D, Fergus S, Vento A, Guirguis A |title=Benefits and Harms of 'Smart Drugs' (Nootropics) in Healthy Individuals |journal=Drugs |volume=82 |issue=6 |pages=633–647 |date=April 2022 |pmid=35366192 |doi=10.1007/s40265-022-01701-7 |hdl=2299/25614 |s2cid=247860331 |hdl-access=free }}</ref>

==Adverse effects==
Modafinil is generally well-tolerated but can have potential risks and side effects. Common adverse effects of modafinil, experienced by less than 10% of users, include [[headache]]s, [[nausea]], and [[Anorexia (symptom)|reduced appetite]].<ref name="pmid18729534" /><ref name="Bello-2015">{{cite book |title=A worldwide yearly survey of new data in adverse drug reactions |vauthors=Bello NT |publisher=Elsevier |year=2015 |isbn=978-0-444-63525-9 |veditors=Ray SD |series=Side Effects of Drugs Annual |volume=37 |pages=1–13 |chapter=Central Nervous System Stimulants and Drugs That Suppress Appetite |doi=10.1016/bs.seda.2015.08.004 |issn=0378-6080}}</ref><ref name="pmid30285371" /> [[Anxiety]], [[insomnia]], [[dizziness]], [[diarrhea]], and [[rhinitis]] are also reported in 5% to 10% of users.<ref name="pmid30285371" /> Psychiatric reactions have occurred in individuals with and without a preexisting psychiatric history.<ref name="Australian Adverse Drug Reactions Bulletin-2008">{{cite web |date=December 1, 2008 |title=Australian Adverse Drug Reactions Bulletin 2008 |url=https://www.tga.gov.au/publication-issue/australian-adverse-drug-reactions-bulletin-vol-27-no-6#a2 |url-status=live |archive-url=https://web.archive.org/web/20200703041749/https://www.tga.gov.au/publication-issue/australian-adverse-drug-reactions-bulletin-vol-27-no-6#a2 |archive-date=July 3, 2020 |publisher=Australian Adverse Drug Reactions Bulletin}}</ref> [[Urinary retention]] and [[paresthesia]] have also been reported.<ref name="Davis2013">{{Cite book | vauthors = Ciccone CD |title=Davis's drug guide for rehabilitation professionals |date=2013 |publisher=F.A. Davis |isbn=978-0-8036-2589-1 |location=Philadelphia |language=en |chapter=Modafinil |chapter-url=https://fadavispt.mhmedical.com/content.aspx?bookid=1873&sectionid=139018549 |archive-url=https://web.archive.org/web/20240916100601/https://fadavispt.mhmedical.com/content.aspx?bookid=1873&sectionid=139018549 |archive-date=2024-09-16 |url-status=live}}</ref>

No significant changes in body weight have been observed in clinical trials, although decreased appetite and weight loss have been noted in children and adolescents.<ref name="Medication Guide-2010">{{cite web |date=November 1, 2010 |title=Provigil |url=http://provigil.com/media/PDFs/medication_guide.pdf |archive-url=https://web.archive.org/web/20160304035819/http://provigil.com/media/PDFs/medication_guide.pdf |archive-date=March 4, 2016 |access-date=December 31, 2013 |work=Medication Guide |publisher=Cephalon, Inc.}}</ref> Modafinil can cause a slight increase in [[Transaminase|aminotransferase enzymes]], indicative of liver function, but there is no evidence of serious liver damage when levels are within reference ranges.<ref name="pmid31643597">{{cite book |title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. |date=2012 |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |location=Bethesda (MD) |chapter=Modafinil |pmid=31643597 |id={{NCBIBook|NBK548274}}}}</ref>

Rare but serious adverse effects include severe skin rashes and allergy-related symptoms. Between December 1998 and January 2007, the FDA received reports of six cases of severe cutaneous adverse reactions, including [[erythema multiforme]], [[Stevens–Johnson syndrome]], [[toxic epidermal necrolysis]], and [[DRESS syndrome]]. The FDA has issued alerts regarding these risks and also noted reports of angioedema and multi-organ hypersensitivity reactions in [[Postmarketing surveillance#United States|postmarketing surveillance]].<ref name="FDA-2007-Serious-Skin-Reactions">{{cite web |year=2007 |title=Modafinil (marketed as Provigil): Serious Skin Reactions |url=http://www.fda.gov/cder/dsn/2007_fall/postmarketing.htm#modafinil |archive-url=https://web.archive.org/web/20090115021301/http://www.fda.gov/cder/dsn/2007_fall/postmarketing.htm#modafinil |archive-date=January 15, 2009 |publisher=U.S. [[Food and Drug Administration]] (FDA)}}</ref><ref name="Li-2023">{{cite news |date=November 6, 2023 |title=Three men hospitalised after taking modafinil or armodafinil to stay awake; drugs were not prescribed |url=https://www.straitstimes.com/singapore/three-men-hospitalised-after-taking-modafinil-or-armodafinil-to-stay-awake-drugs-were-not-prescribed |url-status=live |archive-url=https://web.archive.org/web/20231203191528/https://www.straitstimes.com/singapore/three-men-hospitalised-after-taking-modafinil-or-armodafinil-to-stay-awake-drugs-were-not-prescribed |archive-date=December 3, 2023 |access-date=December 3, 2023 |newspaper=The Straits Times |vauthors=Li TW}}</ref> In 2007, the FDA required Cephalon to modify the Provigil leaflet to include warnings about these serious conditions. The long-term safety and effectiveness of modafinil have not been conclusively established.<ref name="pmid15336235" />

The FDA does not endorse modafinil for children's medical conditions due to an increased risk of rare but serious dermatological toxicity, manifested as [[Stevens–Johnson syndrome]] which is a type of severe skin reaction.<ref name="Fda.gov-2015">{{cite web |date=January 2015 |title=FDA Provigil Drug Safety Data |url=https://www.fda.gov/downloads/Drugs/DrugSafety/UCM231722.pdf |archive-url=https://web.archive.org/web/20170502094203/https://www.fda.gov/downloads/Drugs/DrugSafety/UCM231722.pdf |archive-date=May 2, 2017 |publisher=U.S. [[Food and Drug Administration]] (FDA)}}</ref><ref name="pmid31951804" /><ref name="pmid19300563">{{cite journal |vauthors=Rugino T |date=June 2007 |title=A review of modafinil film-coated tablets for attention-deficit/hyperactivity disorder in children and adolescents |journal=Neuropsychiatric Disease and Treatment |volume=3 |issue=3 |pages=293–301 |pmc=2654790 |pmid=19300563}}</ref> However, in Europe, modafinil may be prescribed for treating narcolepsy in children.<ref name="pmid34173288" />

==Available forms==
[[File:Modafinil 200mg.jpg|thumb|Modafinil tablets – Modalert 200 (Sun Pharma)]]

Modafinil is commercially available in {{Val|100|u=mg}} and {{Val|200|u=mg}} oral tablet forms.<ref name="Provigil FDA label" /> Additionally, it is offered as the (''R'')-[[enantiomer]], known as [[armodafinil]], and as a [[prodrug]] named [[adrafinil]].<ref name="Billiard-2015">{{cite book | vauthors = Billiard M, Lubin S | title=Sleep Medicine | chapter=Modafinil: Development and Use of the Compound | publisher=Springer New York | publication-place=New York, NY | year=2015 | doi=10.1007/978-1-4939-2089-1_61 | pages=541–544| isbn=978-1-4939-2088-4 }}</ref>

==Contraindications==
Modafinil is contraindicated during pregnancy and 2 months before getting pregnant.<ref name="drug-safety-congenital-2020"/> Women who take modafinil should not become pregnant, and, additionally, should be aware that modafinil reduces effectiveness of [[Hormonal contraception|hormonal contraceptives]], increasing chances of getting pregnant.<ref name="Provigil FDA label" /><ref name="medlineplus.gov-modafinil"/><ref name="sleep-women-2016">{{cite journal|title=Sleep Medications and Women: a Review of Issues to Consider for Optimizing the Care of Women with Sleep Disorders| vauthors = Krystal A, Attarian H |date=December 2016|journal=Current Sleep Medicine Reports|volume=2|issue=4|pages=218–222|doi=10.1007/s40675-016-0060-1}}</ref> Modafinil therapy during pregnancy increases the risk of birth defects,<ref name="pmid33074297"/><ref name="pmid33074296">{{cite journal |vauthors=Ghaffari N, Robertson PA |title=Caution in Prescribing Modafinil and Armodafinil to Individuals Who Could Become Pregnant |journal=JAMA Intern Med |volume=181 |issue=2 |pages=277–278 |date=February 2021 |pmid=33074296 |doi=10.1001/jamainternmed.2020.4206 |s2cid=224780160 }}</ref><ref name="birth-defects-2020">{{cite journal | doi=10.1001/jama.2020.9840 | title=Incidence of Malformations After Early Pregnancy Exposure to Modafinil in Sweden and Norway | date=2020 | journal=JAMA | volume=324 | issue=9 | pages=895–897 | pmid=32870289 | pmc=7489822 | vauthors = Cesta CE, Engeland A, Karlsson P, Kieler H, Reutfors J, Furu K }}</ref><ref name="drug-safety-congenital-2020">{{cite web|url=https://www.gov.uk/drug-safety-update/modafinil-provigil-increased-risk-of-congenital-malformations-if-used-during-pregnancy|title=Modafinil (Provigil): increased risk of congenital malformations if used during pregnancy|date=November 16, 2020|website=GOV.UK|access-date=January 13, 2024|archive-date=January 13, 2024|archive-url=https://web.archive.org/web/20240113182538/https://www.gov.uk/drug-safety-update/modafinil-provigil-increased-risk-of-congenital-malformations-if-used-during-pregnancy|url-status=live}}</ref> such as with [[Torticollis|congenital torticollis]], [[hypospadias]], and [[congenital heart defect]]s.<ref name="pmid33074296" />

Modafinil is contraindicated for individuals with known [[hypersensitivity]] to either modafinil or armodafinil.<ref name="Provigil FDA label" /><ref name="pmid22375280" />

Modafinil is also contraindicated in certain cardiac conditions, including uncontrolled moderate to severe [[hypertension]], [[arrhythmia]], [[Pulmonary heart disease|cor pulmonale]],<ref name="Miller-2020"/><ref name="NHS-UK-2022"/> and in cases with signs of CNS stimulant-induced [[mitral valve prolapse]] or [[left ventricular hypertrophy]].<ref name="safety-2015-04-28">{{cite web | url=https://www.acc.org/latest-in-cardiology/articles/2015/04/28/10/06/the-safety-of-stimulant-medication-use-in-cardiovascular-and-arrhythmia-patients | title=The Safety of Stimulant Medication Use in Cardiovascular and Arrhythmia Patients | access-date=January 29, 2024 | archive-date=January 29, 2024 | archive-url=https://web.archive.org/web/20240129013130/https://www.acc.org/latest-in-cardiology/articles/2015/04/28/10/06/the-safety-of-stimulant-medication-use-in-cardiovascular-and-arrhythmia-patients | url-status=live }}</ref><ref name="europa-packaging">{{cite web | title = Modafinil: Annex III Summary of Product Characteristics, Labelling and Package Leaflet | url = https://www.ema.europa.eu/en/documents/referral/modafinil-annex-iii-summary-product-characteristics-labeling-or-package-leaflet_en.pdf | work = European Medicines Agency | access-date = January 29, 2024 | archive-date = January 29, 2024 | archive-url = https://web.archive.org/web/20240129013129/https://www.ema.europa.eu/en/documents/referral/modafinil-annex-iii-summary-product-characteristics-labeling-or-package-leaflet_en.pdf | url-status = live }}</ref> The package insert in the United States cautions about using modafinil in people with a documented medical history of left ventricular hypertrophy or those diagnosed with mitral valve prolapse who have previously exhibited symptoms associated with the mitral valve prolapse syndrome while undergoing treatment involving central nervous system stimulants.<ref name="pmid16199853">{{cite journal |vauthors=Oskooilar N |title=A case of premature ventricular contractions with modafinil |journal=Am J Psychiatry |volume=162 |issue=10 |pages=1983–4 |date=October 2005 |pmid=16199853 |doi=10.1176/appi.ajp.162.10.1983-a }}</ref> The reasons why modafinil is contraindicated in certain cardiac conditions are because modafinil affects the autonomic nervous system and, in particular, exerts significant effects on autonomic cardiovascular regulation, leading in some people to notable increases in heart rate and blood pressure. These substantial changes in the autonomic system warrant careful consideration when prescribing modafinil to people with pre-existing cardiovascular conditions.<ref name="pmid15753235">{{cite journal |vauthors=Taneja I, Diedrich A, Black BK, Byrne DW, Paranjape SY, Robertson D |title=Modafinil elicits sympathomedullary activation |journal=Hypertension |volume=45 |issue=4 |pages=612–8 |date=April 2005 |pmid=15753235 |doi=10.1161/01.HYP.0000158267.66763.63 |s2cid=9192971 |citeseerx=10.1.1.521.5289 }}</ref> The increase in heart rate and blood pressure can worsen the symptoms of such pre-existing conditions as hypertension, arrhythmia, and cor pulmonale. These changes in the autonomic system induced by modafinil can increase the risk of heart attack, stroke, and heart failure. Modafinil can stimulate the release of norepinephrine and epinephrine, hormones that activate the sympathetic nervous system. This can cause [[vasoconstriction]], which is the narrowing of blood vessels, and increase the heart's workload, which is not desired in people with pre-existing heart conditions. In particular, modafinil can worsen the consequences of mitral valve prolapse or left ventricular hypertrophy, which are structural abnormalities of the heart. These can affect the blood flow and oxygen delivery to the heart and other organs.<ref name="pmid15983798">{{cite journal |vauthors=Hou RH, Freeman C, Langley RW, Szabadi E, Bradshaw CM |title=Does modafinil activate the locus coeruleus in man? Comparison of modafinil and clonidine on arousal and autonomic functions in human volunteers |journal=Psychopharmacology (Berl) |volume=181 |issue=3 |pages=537–49 |date=September 2005 |pmid=15983798 |doi=10.1007/s00213-005-0013-8 |s2cid=10265746 }}</ref>

Modafinil is also contraindicated in people with congenital problems like [[galactose]] intolerance, [[lactase deficiency]], or [[glucose-galactose malabsorption]].<ref name="monograph-2">{{cite web | vauthors = Evans K, Tay S | date = September 2020 | title = Shared Care Guideline – Modafinil for narcolepsy (adults) and excessive daytime sleepiness in Parkinson's disease | work = York and Scarborough Medicines Commissioning Committee | url = https://www.yorkandscarboroughformulary.nhs.uk/docs/SC/Modafinil%20shared%20care%20guideline%20v2.pdf | access-date = January 30, 2024 | archive-date = January 30, 2024 | archive-url = https://web.archive.org/web/20240130034658/https://www.yorkandscarboroughformulary.nhs.uk/docs/SC/Modafinil%20shared%20care%20guideline%20v2.pdf | url-status = live }}</ref><ref name="Miller-2020">{{cite web | vauthors = Miller M | veditors = Morgan J | collaboration = Hull & East Riding Prescribing Committee | title = Prescribing Framework for Modafinil for Daytime Hypersomnolence and excessive daytime sleepiness in Parkinsons | url = https://www.hey.nhs.uk/wp/wp-content/uploads/2021/06/modafanil.pdf | location = Northern Lincolnshire, UK | publisher = National Health Service | access-date = December 2, 2023 | archive-date = December 2, 2023 | archive-url = https://web.archive.org/web/20231202001703/https://www.hey.nhs.uk/wp/wp-content/uploads/2021/06/modafanil.pdf | url-status = live }}</ref><ref name="NHS-UK-2022">{{cite web | title = Modafinil for the treatment of adult patients with excessive sleepiness | url = https://gmmmg.nhs.uk/wp-content/uploads/2022/12/GMMMG-Modafinil-primary-care-info-leaflet_Nov-22-approved.pdf | date = November 10, 2022 | publisher = National Health Service, UK | access-date = December 2, 2023 | archive-date = December 2, 2023 | archive-url = https://web.archive.org/web/20231202001703/https://gmmmg.nhs.uk/wp-content/uploads/2022/12/GMMMG-Modafinil-primary-care-info-leaflet_Nov-22-approved.pdf | url-status = live }}</ref>

==Drug tolerance==
Extensive clinical research has not demonstrated [[drug tolerance]] as a common adverse effect, even with therapeutic use extending up to 40 weeks.<ref name="pmid30174215">{{cite journal |vauthors=Billiard M, Broughton R |title=Modafinil: its discovery, the early European and North American experience in the treatment of narcolepsy and idiopathic hypersomnia, and its subsequent use in other medical conditions |journal=Sleep Med |volume=49 |pages=69–72 |date=September 2018 |pmid=30174215 |doi=10.1016/j.sleep.2018.05.027 |s2cid=52143478 }}</ref><ref name="billiard-2016-springer">{{cite book|chapter=Sleep in Narcolepsy and the Effects of Modafinil|vauthors=Billiard M|title=Dopamine and Sleep |doi=10.1007/978-3-319-46437-4_11|date=October 25, 2016|pages=235–253 |publisher=Springer, Cham|isbn=978-3-319-46435-0}}</ref><ref name="pmid15336235">{{cite journal |vauthors=Banerjee D, Vitiello MV, Grunstein RR |title=Pharmacotherapy for excessive daytime sleepiness |journal=Sleep Med Rev |volume=8 |issue=5 |pages=339–54 |date=October 2004 |pmid=15336235 |doi=10.1016/j.smrv.2004.03.002 }}</ref> Drug tolerance in this context is defined as a reduction in response, to wakefulness-promoting and [[pro-motivational agent|anti-fatigue]] properties of modafinil.<ref name="pmid30174215"/>

While modafinil is generally found to be safe and significant adverse effects are rare, including in pediatric narcolepsy cases (sleep disorders in children), there is evidence that long-term usage can lead to tolerance in some individuals.<ref name="pmid32341841" /> This necessitates higher doses to maintain the same level of cognitive enhancement or relief from sleepiness.<ref name="pmid32341841" />

People with current or past substance addictions and those with a family history of addiction are particularly at risk for developing tolerance.<ref name="pmid32341841" /><ref name="pmid34173288"/><ref name="pmid33802176"/>

The mechanisms driving tolerance to modafinil, which may involve its impact on [[dopamine]] and [[norepinephrine]] levels in the brain, are not fully understood.<ref name="pmid32341841" /><ref name="pmid34173288"/><ref name="pmid33802176"/>

Repeated administration of modafinil for off-label use, such as increased [[alertness]] and cognitive-enhancing effects in sleep deprivation, can lead to drug tolerance, which means that the effectiveness of the drug may decrease over time. Still, modafinil therapy as a [[eugeroic]] agent to treat narcolepsy does not typically lead to drug tolerance, i.e., the effectiveness does not usually decrease on prolonged use, although individual responses may vary.<ref name="pmid32341841" /><ref name="pmid34173288">{{cite journal | vauthors = Bassetti CL, Kallweit U, Vignatelli L, Plazzi G, Lecendreux M, Baldin E, Dolenc-Groselj L, Jennum P, Khatami R, Manconi M, Mayer G, Partinen M, Pollmächer T, Reading P, Santamaria J, Sonka K, Dauvilliers Y, Lammers GJ | title = European guideline and expert statements on the management of narcolepsy in adults and children | journal = Journal of Sleep Research | volume = 30 | issue = 6 | article-number = e13387 | date = December 2021 | pmid = 34173288 | doi = 10.1111/jsr.13387 | s2cid = 235648766 | doi-access = free | title-link = doi | hdl = 11380/1251554 | hdl-access = free }}</ref><ref name="pmid33802176">{{cite journal | vauthors = Sharif S, Guirguis A, Fergus S, Schifano F | title = The Use and Impact of Cognitive Enhancers among University Students: A Systematic Review | journal = Brain Sciences | volume = 11 | issue = 3 | page = 355 | date = March 2021 | pmid = 33802176 | pmc = 8000838 | doi = 10.3390/brainsci11030355 | doi-access = free | title-link = doi }}</ref>

==Addiction and dependence==
Despite being a [[CNS stimulant]], the addiction and [[drug dependence|dependence]] liabilities of modafinil are considered low.<ref name="Provigil FDA label" /><ref name="modafinil-schedule-IV-1999">{{cite web|volume=64|issue=17|publisher=Department of Justice|series=Federal register|title=64 FR 4050 - Schedules of Controlled Substances: Placement of Modafinil Into Schedule IV|date=January 27, 1999|vauthors=Sapienza F|url=https://www.govinfo.gov/app/details/FR-1999-01-27/99-1791|access-date=February 5, 2024|archive-date=February 5, 2024|archive-url=https://web.archive.org/web/20240205144036/https://www.govinfo.gov/app/details/FR-1999-01-27/99-1791|url-status=live}}</ref><ref name="pmid33435717" /><ref name="pmid23065655">{{cite journal | vauthors = Mignot EJ | title = A practical guide to the therapy of narcolepsy and hypersomnia syndromes | journal = Neurotherapeutics | volume = 9 | issue = 4 | pages = 739–752 | date = October 2012 | pmid = 23065655 | pmc = 3480574 | doi = 10.1007/s13311-012-0150-9 }}</ref> The exact mechanisms of action of modafinil are not known,<ref name="pmid32032921"/> and it is believed that pharmacological profile of modafinil is different from that of the classical stimulants such as [[cocaine]] or [[amphetamine]].<ref name="pmid22375280"/> Although modafinil shares biochemical mechanisms with stimulant drugs, it is less likely to have [[Mood elevation|mood-elevating properties]].<ref name="Provigil FDA label" /> The similarities in effects with [[caffeine]] are not clearly established.<ref name= "pmid22375280"/><ref name="Warot-1993">{{cite journal|vauthors=Warot D, Corruble E, Payan C, Weil JS, Puech AJ|date=1993|title=Subjective effects of modafinil, a new central adrenergic stimulant in healthy volunteers: a comparison with amphetamine, caffeine, and placebo|journal=European Psychiatry |volume=8|issue=4|pages=201–208|doi=10.1017/S0924933800002923|s2cid=151797528 }}</ref> Unlike other stimulants, modafinil does not induce a strong subjective [[Pleasure|feeling of pleasure or reward]], which is commonly associated with [[euphoria]], an intense feeling of well-being.<ref name="pmid32341841"/> Euphoria may be an indicator of a drug's potential to be abused. Substance abuse is a compulsive and excessive use of the substance despite adverse consequences.<ref name="pmid22542906">{{cite journal |vauthors=de Wit H, Phillips TJ |title=Do initial responses to drugs predict future use or abuse? |journal=Neurosci Biobehav Rev |volume=36 |issue=6 |pages=1565–76 |date=July 2012 |pmid=22542906 |pmc=3372699 |doi=10.1016/j.neubiorev.2012.04.005 }}</ref> In comparison to classical stimulants, modafinil exhibits a low propensity for abuse, as it lacks significantly expressed pleasurable or euphoric effects.<ref name="pmid32341841"/> Albeit to a lower degree than classical stimulants, modafinil still can produce psychoactive, euphoric, and subjective effects typical for abused stimulants.<ref name="Provigil FDA label"/><ref name="Drugs.com-Monograph-2023"/>

Modafinil was not observed to promote overuse or misuse, even in people who have a history of cocaine addiction.<ref name="pmid16741217">{{cite journal | vauthors = O'Brien CP, Dackis CA, Kampman K | title = Does modafinil produce euphoria? | journal = The American Journal of Psychiatry | volume = 163 | issue = 6 | page = 1109 | date = June 2006 | pmid = 16741217 | doi = 10.1176/ajp.2006.163.6.1109 }}</ref> Despite the initial belief that modafinil carried no abuse potential, emerging evidence suggests that it works at the same neurobiological mechanisms as other addictive stimulants. Consequently, there exists a potential risk of modafinil abuse, necessitating prudent consideration and caution when prescribing or using this medication.<ref name="pmid35366192"/> Modafinil exhibits a lower response on the amphetamine scale of the addiction research center inventory, suggesting reduced propensity for abuse compared to amphetamine.<ref name="pmid35990796">{{cite journal |vauthors=Martins B, Rutland W, De Aquino JP, Kazer BL, Funaro M, Potenza MN, Angarita GA |title=Helpful or Harmful? The Therapeutic Potential of Medications with Varying Degrees of Abuse Liability in the Treatment of Substance Use Disorders |journal=Curr Addict Rep |volume=9 |issue=4 |pages=647–659 |date=2022 |pmid=35990796 |pmc=9376579 |doi=10.1007/s40429-022-00432-9 }}</ref>

The US [[Drug Enforcement Administration]] has classified modafinil as a [[Controlled Substances Act#Schedule IV controlled substances|Schedule IV controlled substance]];<ref name="modafinil-schedule-IV-1999"/><ref name="Provigil FDA label" /> the medicine is recognized for having valid medical uses with low addiction potential.<ref name="pmid23065655" /><ref name="pmid16669720"/> The [[International Narcotics Control Board]] does not classify it as a narcotic or a psychotropic substance.<ref name="INCB yellow">{{cite web | publisher= [[International Narcotics Control Board]] |title=Yellow List: List of Narcotic Drugs Under International Control |series=In accordance with the Single Convention on Narcotic Drugs, 1961 [Protocol of March 25, 1972, amending the Single Convention on Narcotic Drugs, 1961] |date=July 2020 |edition=59th |url=https://www.incb.org/incb/en/narcotic-drugs/Yellowlist/yellow-list.html |access-date=January 12, 2022 |archive-date=January 16, 2022 |archive-url=https://web.archive.org/web/20220116102908/https://www.incb.org/incb/en/narcotic-drugs/Yellowlist/yellow-list.html }}</ref><ref name="INCB green">{{cite web | publisher= International Narcotics Control Board |title=Green List: List of Psychotropic Substances Under International Control |series=In accordance with Convention psychotropic substances of 1971 |date=July 2020 |edition=31st |url= https://www.incb.org/incb/en/psychotropics/toolkit.html |access-date=January 12, 2022 |archive-date=January 18, 2022 |archive-url= https://web.archive.org/web/20220118201426/https://www.incb.org/incb/en/psychotropics/toolkit.html |url-status=live }}</ref>

==Overdose==
An [[Drug overdose|overdose]] of modafinil can lead to a range of symptoms and complications. Psychiatric symptoms may include [[psychosis]], [[mania]], [[hallucination]]s, and [[suicidal ideation]], which can occur even in individuals without a history of mental illness and may persist after discontinuation of the drug.<ref name="pmid31422705">{{cite journal | vauthors = Reinert JP, Dunn RL | title = Management of overdoses of loperamide, gabapentin, and modafinil: a literature review | journal = Expert Review of Clinical Pharmacology | volume = 12 | issue = 9 | pages = 901–908 | date = September 2019 | pmid = 31422705 | doi = 10.1080/17512433.2019.1657830 | s2cid = 201063075 }}</ref> Neurological complications, such as seizures, tremors, [[dystonia]], and [[dyskinesia]], may arise from modafinil's interaction with various neurotransmitter systems.<ref name="pmid31422705" />

Allergic reactions such as rash, [[angioedema]], [[anaphylaxis]], and [[Stevens–Johnson syndrome]] may rarely be triggered by an immunological response to modafinil or its metabolites.<ref name="pmid29028129">{{cite journal | vauthors = Prince V, Philippidou M, Walsh S, Creamer D | title = Stevens-Johnson syndrome induced by modafinil | journal = Clinical and Experimental Dermatology | volume = 43 | issue = 2 | pages = 191–192 | date = March 2018 | pmid = 29028129 | doi = 10.1111/ced.13282 | s2cid = 204987385 }}</ref><ref name="Reactions-Weekly-2018-Overdose">{{cite journal|doi=10.1007/s40278-018-42202-6 |title=Modafinil overdose |journal=Reactions Weekly |date=2018 |volume=1690 |page=136 |s2cid=195079873 }}</ref> Cardiovascular complications like hypertension, [[tachycardia]], chest pain, and [[arrhythmia]]s may also be observed due to modafinil's sympathomimetic action.<ref name="pmid31422705"/>

In animal studies, the median lethal dose (LD<sub>50</sub>) of modafinil varies among species and depends on the route of administration. In mice and rats, the LD<sub>50</sub> is approximately {{Val|1250|u=mg/kg}} if administered via an injection, but the oral LD<sub>50</sub> for rats is {{Val|3400|u=mg/kg}}.<ref name="adrafinil1999">{{cite journal |title=Adrafinil: A Novel Vigilance Promoting Agent|vauthors=Milgram NW, Callahan H, Siwak C|date=September 1999|journal=CNS Drug Reviews|volume=5|issue=3|pages=193–212|doi=10.1111/j.1527-3458.1999.tb00100.x }}</ref><ref name="modafinil-mesenchymal-2020">{{cite journal | vauthors = Nazarian S, Abdolmaleki Z, Torfeh A, Shirazi Beheshtiha SH | title = Mesenchymal stem cells with modafinil (gold nanoparticles) significantly improves neurological deficits in rats after middle cerebral artery occlusion | journal = Experimental Brain Research | volume = 238 | issue = 11 | pages = 2589–2601 | date = November 2020 | pmid = 32886135 | doi = 10.1007/s00221-020-05913-9 | s2cid = 221495887 }}</ref> The LD<sub>50</sub> value for humans have not been established. Human clinical trials have involved total daily doses up to {{Val|1200|u=mg/day}} for 7–21&nbsp;days. Acute one-time total overdoses up to {{Val|4500|u=mg}} have not been life-threatening but resulted in symptoms like [[psychomotor agitation|agitation]], [[insomnia]], [[tremor]], [[palpitations]], and [[gastrointestinal disturbances]].<ref name="Provigil FDA label" /><ref name="pmid23757186">{{cite journal | vauthors = Spiller HA, Hays HL, Aleguas A | title = Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management | journal = CNS Drugs | volume = 27 | issue = 7 | pages = 531–543 | date = July 2013 | pmid = 23757186 | doi = 10.1007/s40263-013-0084-8 }}</ref>

The management of modafinil overdose involves supportive care, monitoring of vital signs, and treatment of specific complications. In cases of recent consumption, [[activated charcoal]], [[gastric lavage]], or [[hemodialysis]] may be used.<ref name="pmid31422705"/> There is no specific antidote for modafinil overdose.<ref name="pmid23757186" /><ref name="Reactions-Weekly-2018-Misuse-Abuse">{{cite journal|doi=10.1007/s40278-018-52897-7|title=Modafinil overdose/misuse/abuse|journal=Reactions Weekly|volume=1723|page=215|year=2018|s2cid=195081462 }}</ref><ref name="pmid18787992">{{cite journal | vauthors = Spiller HA, Borys D, Griffith JR, Klein-Schwartz W, Aleguas A, Sollee D, Anderson DA, Sawyer TS | title = Toxicity from modafinil ingestion | journal = Clinical Toxicology | volume = 47 | issue = 2 | pages = 153–156 | date = February 2009 | pmid = 18787992 | doi = 10.1080/15563650802175595 | s2cid = 12421545 }}</ref> The main way to deal with modafinil overdose is supportive care, which includes sedating the patient and stabilizing their blood pressure, and muscle activity in case of manifestations such as agitation or tremor.<ref name="pmid23757186"/>

== Interactions ==
Some of the drugs that frequently interact with modafinil include [[aripiprazole]] (an antipsychotic), [[amphetamine]] (including its enantiomers and salts; stimulants), [[aspirin]], and others.<ref name="Modafinil Interactions Checker">{{cite web | url=https://www.drugs.com/drug-interactions/modafinil.html | title=Modafinil Interactions | work=Drugs.com | date=January 10, 2024 | access-date=February 5, 2024 | archive-date=December 15, 2023 | archive-url=https://web.archive.org/web/20231215212735/https://www.drugs.com/drug-interactions/modafinil.html | url-status=live }}</ref>

Modafinil is a weak to moderate [[enzyme inducer|inducer]] of [[CYP3A4]]<ref name="sleep-women-2016" /><ref name="FDA-2021">{{cite web | url=https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers | title=Drug Development and Drug Interactions &#124; Table of Substrates, Inhibitors and Inducers | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=May 26, 2021 | access-date=April 8, 2022 | archive-date=November 4, 2020 | archive-url=https://web.archive.org/web/20201104173036/https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers }}</ref><ref name="UpToDate-CYP3A4">{{cite web | url = https://www.uptodate.com/contents/image?imageKey=CARD%2F76992 | title = Cytochrome P450 3A (including 3A4) inhibitors and inducers | work = UpToDate | access-date = April 8, 2022 | archive-date = April 8, 2022 | archive-url = https://web.archive.org/web/20220408220537/https://www.uptodate.com/contents/image?imageKey=CARD%2F76992 | url-status = live }}</ref> and a weak inhibitor of [[CYP2C19]],<ref name="pmid12537513"/> enzymes of the [[cytochrome P450]] group of enzymes.<ref name="pmid30285371"/> Modafinil also induces or inhibits other cytochrome P450 enzymes.<ref name="sleep-women-2016" /> One ''[[in vitro]]'' study predicts that modafinil may [[enzyme inducer|induce]] the cytochrome P450 enzymes [[CYP1A2]], CYP3A4, and [[CYP2B6]], as well as may inhibit [[CYP2C9]] and [[CYP2C19]].<ref name="pmid10820139" /> However, other in-vitro studies find no significant inhibition of [[CYP2C9]].<ref name="pmid12537513"/><ref name="pmid11831544">{{cite journal | vauthors = Robertson P, Hellriegel ET, Arora S, Nelson M | title = Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers | journal = Journal of Clinical Pharmacology | volume = 42 | issue = 2 | pages = 205–214 | date = February 2002 | pmid = 11831544 | doi = 10.1177/00912700222011120 | s2cid = 29223738 }}</ref> Modafinil may induce [[P-glycoprotein]], which may affect drugs transported by P-glycoprotein, such as [[digoxin]].<ref name="pmid17963743">{{cite journal | vauthors = Zhu HJ, Wang JS, Donovan JL, Jiang Y, Gibson BB, DeVane CL, Markowitz JS | title = Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein | journal = European Journal of Pharmacology | volume = 578 | issue = 2–3 | pages = 148–158 | date = January 2008 | pmid = 17963743 | pmc = 2659508 | doi = 10.1016/j.ejphar.2007.09.035 }}</ref>

It was clinically found that modafinil affects [[pharmacodynamics]] of drugs which are metabolized by CYP3A4 and other enzymes of the cytochrome P450 family so that interactions of modafinil with these drugs were observed in real people, rather than being predicted in a lab setting.<ref name="sleep-women-2016" /><ref name="FDA-2021" /> For instance, it was observed that induction of CYP3A4 by modafinil affects metabolism of the following [[medication]]s and [[endogenous]] substances:<ref name="Drugs.com-Interactions-2021" />
* '''[[opioid]]s''', such as [[methadone]], [[hydrocodone]], [[oxycodone]], or [[fentanyl]] – modafinil may result in a drop in opioid plasma concentrations because of faster clearance of opioids by CYP3A4. If the patient is not monitored closely, reduced efficacy or withdrawal symptoms can occur.<ref name="Drugs.com-Interactions-2021">{{cite web |title=Modafinil drug interactions |url=https://www.drugs.com/drug-interactions/modafinil-index.html |website=Drugs.com |access-date=May 3, 2021 |archive-date=May 3, 2021 |archive-url=https://web.archive.org/web/20210503184406/https://www.drugs.com/drug-interactions/modafinil-index.html |url-status=live }}</ref>
* '''[[steroid]] hormones''', such as [[estradiol]], [[progesterone]] or [[cortisol]]. Modafinil may have an adverse effect on [[Hormonal contraception|hormonal contraceptives]] (such as [[Oral contraceptive pill|birth control pills]], [[Patch (dermatology)|patches]], etc.) for up to a month after discontinuation.<ref name="NIH-2005">{{cite web |url=https://www.medlineplus.gov/druginfo/meds/a602016.html | work = Medline Plus | publisher = U.S. National Library of Medicine | title = Modafinil |date=July 1, 2005 |access-date=July 21, 2007 |url-status=live |archive-url=https://web.archive.org/web/20070610045952/http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a602016.html |archive-date=June 10, 2007}}</ref> Both modafinil and armodafinil in the United States and the United Kingdom come with package inserts that highlight the interaction between these medications and hormonal birth control.<ref name="sleep-women-2016" /> Modafinil may induce cytochrome P450 enzymes that are involved in the clearance of steroid hormones taken as hormonal contraceptives, reducing their effectiveness, which may lead to pregnancy despite taking the birth control medication. Besides steroid hormones, modafinil may affect [[pituitary gland]] hormones. In a 2006 study, a single dose of modafinil {{Val|200|u=mg}} caused a decrease in blood [[prolactin]] levels, although it did not affect [[human growth hormone]] or [[thyroid-stimulating hormone]].<ref name="pmid17712350">{{cite journal | vauthors = Minzenberg MJ, Carter CS | title = Modafinil: a review of neurochemical actions and effects on cognition | journal = Neuropsychopharmacology | volume = 33 | issue = 7 | pages = 1477–1502 | date = June 2008 | pmid = 17712350 | doi = 10.1038/sj.npp.1301534 | publisher = Springer Science and Business Media LLC | s2cid = 13752498 | doi-access = free | title-link = doi }}</ref><ref name="pmid16401653">{{cite journal | vauthors = Samuels ER, Hou RH, Langley RW, Szabadi E, Bradshaw CM | title = Comparison of pramipexole and modafinil on arousal, autonomic, and endocrine functions in healthy volunteers | journal = Journal of Psychopharmacology | volume = 20 | issue = 6 | pages = 756–770 | date = November 2006 | pmid = 16401653 | doi = 10.1177/0269881106060770 | publisher = SAGE Publications | s2cid = 8033437 }}</ref> Since modafinil induces the activity of the CYP3A4 enzyme involved in [[cortisol]] clearance,<ref name="pmid25678418">{{cite journal | vauthors = Niwa T, Murayama N, Imagawa Y, Yamazaki H | title = Regioselective hydroxylation of steroid hormones by human cytochromes P450 | journal = Drug Metabolism Reviews | volume = 47 | issue = 2 | pages = 89–110 | date = May 2015 | pmid = 25678418 | doi = 10.3109/03602532.2015.1011658 | publisher = Informa UK Limited | s2cid = 5791536 }}</ref> modafinil may reduce the bioavailability of [[hydrocortisone]]. Therefore, it may be necessary to adjust the steroid substitution dose in people receiving modafinil, which is a CYP3A4-metabolism-inducing drug.<ref name="pmid34633961">{{cite journal | vauthors = Aquinos BM, García Arabehety J, Canteros TM, de Miguel V, Scibona P, Fainstein-Day P | title = [Adrenal crisis associated with modafinil use] | language = es | journal = Medicina | volume = 81 | issue = 5 | pages = 846–849 | year = 2021 | pmid = 34633961 }}</ref>

[[Hypertensive crisis|Hypertensive crises]] have been reported when [[armodafinil]] (one of modafinil's [[enantiomer]]s) has been taken with [[monoamine oxidase inhibitor]]s (MAOIs) like [[tranylcypromine]].<ref name="KinslowShapiroGrunebaum2018">{{cite journal | vauthors = Kinslow CJ, Shapiro SD, Grunebaum MF, Miller EC | title = Acute hypertensive crisis and severe headache after concurrent use of armodafinil and tranylcypromine: Case report and review of the literature | journal = J Neurol Sci | volume = 393 | issue = | pages = 1–3 | date = October 2018 | pmid = 30077942 | pmc = 6446082 | doi = 10.1016/j.jns.2018.07.023 | url = }}</ref>

==Pharmacology==
===Pharmacodynamics===
{| class="wikitable floatright"
|+ Modafinil activity profile
|-
! Site !! Potency !! Type !! Species !! Refs
|-
| {{Abbrlink|DAT|Dopamine transporter}} || {{Val|1.8|-|2.6|u=μM}}<br />{{Val|4.8|u=μM}}<br />{{Val|6.4|u=μM}}<br />{{Val|4.0|u=μM}}|| K<sub>i</sub><br />K<sub>i</sub><br />IC<sub>50</sub><sup>a</sup><br />IC<sub>50</sub><sup>a</sup> || Human<br />Rat<br />Human<br />Rat || <ref name="pmid19197004">{{cite journal | vauthors = Zolkowska D, Jain R, Rothman RB, Partilla JS, Roth BL, Setola V, Prisinzano TE, Baumann MH | title = Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 329 | issue = 2 | pages = 738–746 | date = May 2009 | pmid = 19197004 | pmc = 2672878 | doi = 10.1124/jpet.108.146142 | author5-link = Bryan Roth }}</ref><ref name="pmid34423920">{{cite journal | vauthors = Krief S, Berrebi-Bertrand I, Nagmar I, Giret M, Belliard S, Perrin D, Uguen M, Robert P, Lecomte JM, Schwartz JC, Finance O, Ligneau X | title = Pitolisant, a wake-promoting agent devoid of psychostimulant properties: Preclinical comparison with amphetamine, modafinil, and solriamfetol | journal = Pharmacology Research & Perspectives | volume = 9 | issue = 5 | article-number = e00855 | date = October 2021 | pmid = 34423920 | pmc = 8381683 | doi = 10.1002/prp2.855 }}</ref><br /><ref name="pmid19197004" /><br /><ref name="pmid29115823">{{cite journal | vauthors = Murillo-Rodríguez E, Barciela Veras A, Barbosa Rocha N, Budde H, Machado S | title = An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil | journal = ACS Chemical Neuroscience | volume = 9 | issue = 2 | pages = 151–158 | date = February 2018 | pmid = 29115823 | doi = 10.1021/acschemneuro.7b00374 }}</ref><ref name="pmid22537794">{{cite journal | vauthors = Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, Kopajtic T, Shi L, Katz JL, Tanda G, Newman AH | title = R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse | journal = Biological Psychiatry | volume = 72 | issue = 5 | pages = 405–413 | date = September 2012 | pmid = 22537794 | pmc = 3413742 | doi = 10.1016/j.biopsych.2012.03.022 }}</ref><br /><ref name="pmid19197004" />
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || &gt;{{Val|10|u=μM}}<br />&gt;{{Val|92|u=μM}}<br />{{Val|35.6|u=μM}}<br />{{Val|136|u=μM}} || K<sub>i</sub><br />K<sub>i</sub><br />IC<sub>50</sub><sup>a</sup><br />IC<sub>50</sub><sup>a</sup> || Human<br />Rat<br />Human<br />Rat || <ref name="pmid19197004" /><ref name="pmid34423920" /><br /><ref name="pmid19197004" /><br /><ref name="pmid29115823" /><ref name="pmid22537794" /><br /><ref name="pmid19197004" />
|-
| {{Abbrlink|SERT|Serotonin transporter}} || >{{Val|10|u=μM}}<br />{{Val|46.6|u=μM}}<br />&gt;{{Val|500|u=μM}}<br />&gt;{{Val|50|u=μM}} || K<sub>i</sub><br />K<sub>i</sub><br />IC<sub>50</sub><sup>a</sup><br />IC<sub>50</sub><sup>a</sup> || Human<br />Rat<br />Human<br />Rat || <ref name="pmid19197004" /><ref name="pmid34423920" /><br /><ref name="pmid19197004" /><br /><ref name="pmid29115823" /><ref name="pmid22537794" /><br /><ref name="pmid19197004" />
|-
| [[Dopamine D2 receptor|D<sub>2</sub>]] || >{{Val|10|u=μM}}<br />{{Val|16|u=μM}}<sup>b</sup><br />{{Val|120|u=μM}}<sup>b</sup> || K<sub>i</sub><br />K<sub>i</sub><br />EC<sub>50</sub><sup>a</sup> || Human<br />Rat<br />Rat|| <ref name="pmid19197004" /><br /><ref name="pmid19391150">{{cite journal | vauthors = Seeman P, Guan HC, Hirbec H | title = Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil | journal = Synapse | volume = 63 | issue = 8 | pages = 698–704 | date = August 2009 | pmid = 19391150 | doi = 10.1002/syn.20647 | s2cid = 17758902 }}</ref><br /><ref name="pmid19391150" />
|- class="sortbottom"
| colspan="5" style="width:1px; background:#eaecf0; text-align:center;"| '''Footnotes:''' <sup>a</sup> = Functional activity, not binding inhibition. <sup>b</sup> = [[Armodafinil]] at D<sub>2</sub><sup>High</sup>. '''Notes:''' No activity at a variety of other assessed targets.<ref name="pmid19197004" />
|}

The precise [[mechanism of action]] of modafinil for narcolepsy and other sleep disorders remains unclear.<ref name="Drugs.com-Monograph-2023"/><ref name="pmid32032921">{{cite journal | vauthors = Thorpy MJ, Bogan RK | title = Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications | journal = Sleep Medicine | volume = 68 | pages = 97–109 | date = April 2020 | pmid = 32032921 | doi = 10.1016/j.sleep.2019.09.001 | s2cid = 203405397 }}</ref><ref name="Stahl-2017">{{cite book | vauthors=Stahl SM | title=Prescriber's Guide: Stahl's Essential Psychopharmacology | date=March 2017 | publisher=Cambridge University Press | location=Cambridge, United Kingdom | isbn=978-1-108-22874-9 | pages=491–495 | edition=6th | chapter=Modafinil }}</ref><ref name="pmid19300566">{{cite journal | vauthors = Gerrard P, Malcolm R | title = Mechanisms of modafinil: A review of current research | journal = Neuropsychiatric Disease and Treatment | volume = 3 | issue = 3 | pages = 349–364 | date = June 2007 | pmid = 19300566 | pmc = 2654794 }}</ref> Although modafinil may have interactions with neurotransmitter systems, its exact mode of action is not fully understood.<ref name="pmid32032921"/><ref name="pmid28646346">{{cite book | vauthors = Lazarus M, Chen JF, Huang ZL, Urade Y, Fredholm BB | chapter = Adenosine and Sleep | title = Handbook of Experimental Pharmacology | volume = 253 | pages = 359–381 | date = 2019 | pmid = 28646346 | doi = 10.1007/164_2017_36 | isbn = 978-3-030-11270-7 }}</ref>

From laboratory research, modafinil has little to no affinity for [[Serotonin transporter|serotonin]] or [[norepinephrine transporter]]s and does not directly interact with these systems.<ref name="pmid30285371"/><ref name="pmid19300566"/> However, studies have shown that elevated concentrations of norepinephrine and serotonin can occur as an indirect effect following modafinil administration due to increased extracellular dopamine activity.<ref name="pmid19300566"/><ref name="pmid30285371"/> Unlike traditional psychostimulant drugs,<ref name="pmid38725665"/> such as [[cocaine]] or [[amphetamine]], modafinil shows low potential for causing euphoria due to differences in how it interacts with dopamine transporters at a cellular level.<ref name="pmid32032921"/><ref name="pmid19300566"/><ref name="pmid28646346"/>

In addition to its influence on [[dopaminergic pathways]], modafinil may impact other neurotransmitter systems, such as [[orexin]] ([[hypocretin]]).<ref name="pmid19300566"/> Orexin neurons are involved in promoting wakefulness and regulating arousal states. Modafinil may increase signaling within hypothalamic orexin pathways, potentially contributing to its wake-promoting effects.<ref name="pmid30285371"/><ref name="pmid19300566"/>

===Pharmacokinetics===
C<sub>max</sub> (peak levels) occurs approximately 2&nbsp;to&nbsp;3&nbsp;hours after modafinil administration.<ref name="pmid12537513"/> Food slows the absorption of modafinil but does not affect the total [[Area under the curve (pharmacokinetics)|area under the curve]] (AUC). ''In vitro'' measurements indicate that 60% of modafinil is bound to [[plasma protein]]s at clinical concentrations of the drug. This percentage changes very little when the concentration of modafinil is varied.<ref name="Hardman2001">{{cite book |vauthors=Gilman A, Goodman LS, Hardman JG, Limbird LE |title=Goodman & Gilman's the pharmacological basis of therapeutics |publisher=McGraw-Hill |location=New York |year=2001 |page=1984 |isbn=978-0-07-135469-1 }}</ref>

Renal excretion of unchanged modafinil usually accounts for less than 10% of an oral dose. This means that when modafinil is taken by mouth, the only approved route of administration, less than 10% of the drug is eliminated from the body through the urine without being metabolized by the liver or other organs. The rest of the drug is either metabolized or excreted through other routes, such as feces or bile.<ref name="pmid12537513"/>

The two major circulating [[metabolite]]s of modafinil are [[modafinil acid]] (CRL-40467) and [[modafinil sulfone]] (CRL-41056). Both of these metabolites have been described as inactive, and neither appears to contribute to the wakefulness-promoting effects of modafinil.<ref name="pmid31951804"/><ref name="pmid26908128">{{cite journal | vauthors = Ramachandra B | title = A Critical Review of Properties of Modafinil and Analytical, Bioanalytical Methods for its Determination | journal = Critical Reviews in Analytical Chemistry | volume = 46 | issue = 6 | pages = 482–489 | date = November 2016 | pmid = 26908128 | doi = 10.1080/10408347.2016.1153948 | s2cid = 34069997 }}</ref> However, modafinil sulfone does appear to possess [[anticonvulsant]] effects, a property that it shares with modafinil.<ref name="pmid31951804"/><ref name="pmid15260124">{{cite journal | vauthors = Chatterjie N, Stables JP, Wang H, Alexander GJ | title = Anti-narcoleptic agent modafinil and its sulfone: a novel facile synthesis and potential anti-epileptic activity | journal = Neurochemical Research | volume = 29 | issue = 8 | pages = 1481–1486 | date = August 2004 | pmid = 15260124 | doi = 10.1023/b:nere.0000029559.20581.1a | s2cid = 956077 }}</ref>

[[Elimination half-life]] is in the range of 10 to 12 hours,<ref name="pmid12537513"/><ref name="Hardman2001"/> subject to differences in sex,<ref name="sleep-women-2016"/> in cytochrome P450 [[genotype]]s, liver function and renal function. Modafinil is metabolized mainly in the liver,<ref name="pmid12537513"/> and its inactive metabolites are excreted in the urine. Urinary excretion of the unchanged drug is usually less than 10% but can range from 0% to as high as 18.7%, depending on the factors mentioned.<ref name="Hardman2001"/>

Modafinil exhibits sex-specific pharmacokinetic differences.<ref name="sleep-women-2016" /> It demonstrates higher [[bioavailability]] in women compared to men. The mean C<sub>max</sub> is higher in women than in men, {{Val|5.2|u=mg/L}} vs. {{Val|4.2|u=mg/L}} (p < 0.05), following a single {{Val|200|u=mg}} oral dose of modafinil.<ref name="sleep-women-2016" /> This difference persists even after adjusting for body weight ({{Val|0.88|u=ml/min/kg}} vs. {{Val|0.72|u=ml/min/kg}}).<ref name="sleep-women-2016" /> The clearance of modafinil is 30% higher in men than in women, and plasma concentrations after a single dose are significantly higher in women than in men. These sex-specific pharmacokinetic differences may have implications for the efficacy and safety of modafinil.<ref name="sleep-women-2016" />

==Chemistry==
===Enantiomers===
<div class="skin-invert-image">{{Multiple image
| direction  = horizontal
| align      = right
| image1     = (R)-(−)-modafinil.svg
| width1     = 180
| caption1   = [[Armodafinil]] ((''R'')-(−)-modafinil)
| image2     = (S)-(+)-modafinil.svg
| width2     = 180
| caption2   = [[Esmodafinil]] ((''S'')-(+)-modafinil)
}}</div>

Modafinil is a [[racemic mixture]] of two [[enantiomer]]s, [[armodafinil]] ((''R'')-modafinil) and [[esmodafinil]] ((''S'')-modafinil).<ref name="pmid20307223">{{cite journal | vauthors = Bogan RK | title = Armodafinil in the treatment of excessive sleepiness | journal = Expert Opinion on Pharmacotherapy | volume = 11 | issue = 6 | pages = 993–1002 | date = April 2010 | pmid = 20307223 | pmc = 3630938 | doi = 10.1517/14656561003705738 }}</ref>

===Detection in body fluids===
Modafinil and/or its major metabolite, modafinil acid, may be quantified in plasma, serum, or urine to monitor dosage in those receiving the drug therapeutically, to confirm a diagnosis of poisoning in hospitalized patients, or to assist in the forensic investigation of a vehicular traffic violation.<ref name="judexbelarus-2018">{{cite journal|url=https://elibrary.ru/item.asp?id=36403188|title=Analytical characteristics and identification of modafinil and adrafinil in the objects of examination|vauthors=Polyakov YS, Mikhniuk ON, Hilkevich TY, Chevtchouk TA, Yurchenko RA, Vinarskiy VA|publisher=State Institute for Advanced Training and Retraining of Customs Authorities of the Republic of Belarus|issn=2413-6158|journal=Судебная экспертиза Беларуси|year=2018|access-date=February 6, 2024|archive-date=September 28, 2020|archive-url=https://web.archive.org/web/20200928001949/https://www.elibrary.ru/item.asp?id=36403188|url-status=live}}</ref> Instrumental techniques involving gas or liquid chromatography are usually employed for these purposes.<ref name="pmid16142993"/><ref name="pmid9549666">{{cite journal | vauthors = Wong YN, King SP, Laughton WB, McCormick GC, Grebow PE | title = Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers | journal = Journal of Clinical Pharmacology | volume = 38 | issue = 3 | pages = 276–282 | date = March 1998 | pmid = 9549666 | doi = 10.1002/j.1552-4604.1998.tb04425.x | s2cid = 26877375 }}</ref><ref name="Baselt-2008">{{cite book | vauthors = Baselt RC |title=Disposition of Toxic Drugs and Chemicals in Man |publisher=Biomedical Publications |location=Foster City, CA |year=2008 |isbn=978-0-9626523-7-0 |pages=1152–1153}}</ref> In 2011, modafinil was not tested for by common [[Drug test|drug screens]] (except for anti-doping screens) and is unlikely to cause false positives for other chemically unrelated drugs such as [[substituted amphetamine]]s.<ref name="pmid22537794"/><ref name="pmid20307223" /><ref name="mdpi-advanced-mass-spectrometry" />

[[Reagent testing]] can screen for the presence of modafinil in samples.<ref name="Spratley-2005"/><ref name="Reagent Tests UK-2015"/>

{| class="wikitable"
|+ Colors produced by modafinil with various reagents
|-
!RC
![[Marquis reagent|Marquis Reagent]]
![[Liebermann reagent|Liebermann]]
![[Froehde reagent|Froehde]]
|-
|Modafinil || Yellow/Orange > Brown<ref name="Spratley-2005"/><ref name="Reagent Tests UK-2015"/> || Darkening Orange<ref name="Spratley-2005">{{cite journal | vauthors = Spratley TK, Hayes PA, Geer LC, Cooper SD, McKibben TD | title = Analytical Profiles for Five "Designer" Tryptamines | journal = Microgram Journal | volume = 3 | issue = 1–2 | pages = 54–68 | year = 2005 | format = PDF | url = http://www.erowid.org/library/periodicals/microgram/microgram_journal_2005-1.pdf#page=54 | access-date = December 18, 2015 | archive-date = August 2, 2020 | archive-url = https://web.archive.org/web/20200802180946/https://www.erowid.org/library/periodicals/microgram/microgram_journal_2005-1.pdf#page=54 | url-status = live }}</ref> || Deep orange/red<ref name="Reagent Tests UK-2015">{{cite web | url=http://www.reagent-tests.uk/blog/modafinil-reaction-with-the-froehde-reagent-and-others/ | title=Modafinil reaction with the Froehde reagent and others | publisher=Reagent Tests UK | date=December 13, 2015 | access-date=December 18, 2015 | archive-date=August 3, 2020 | archive-url=https://web.archive.org/web/20200803124145/https://www.reagent-tests.uk/blog/modafinil-reaction-with-the-froehde-reagent-and-others/ | url-status=live }}</ref>
|}

===Structural analogs===
{{See also|List of modafinil analogues and derivatives}}

Many [[chemical derivative|derivative]]s and [[structural analog]]s of modafinil have been synthesized.<ref name="pmid32927246"/><ref name="pmid18954992">{{cite journal | vauthors = De Risi C, Ferraro L, Pollini GP, Tanganelli S, Valente F, Veronese AC | title = Efficient synthesis and biological evaluation of two modafinil analogues | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 23 | pages = 9904–9910 | date = December 2008 | pmid = 18954992 | doi = 10.1016/j.bmc.2008.10.027 }}</ref><ref name="pmid24494745">{{cite journal | vauthors = Okunola-Bakare OM, Cao J, Kopajtic T, Katz JL, Loland CJ, Shi L, Newman AH | title = Elucidation of structural elements for selectivity across monoamine transporters: novel 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues | journal = Journal of Medicinal Chemistry | volume = 57 | issue = 3 | pages = 1000–1013 | date = February 2014 | pmid = 24494745 | pmc = 3954497 | doi = 10.1021/jm401754x }}</ref> Examples include [[adrafinil]], [[CE-123]], [[fladrafinil]] (CRL-40941; fluorafinil), [[flmodafinil]] (CRL-40940; bisfluoromodafinil, lauflumide), [[RDS03-94]], [[JJC8-088]], [[modafiendz]] and [[modafinil sulfone]] (CRL-41056).<ref name="pmid33024436">{{cite journal | vauthors = Napoletano F, Schifano F, Corkery JM, Guirguis A, Arillotta D, Zangani C, Vento A | title = The Psychonauts' World of Cognitive Enhancers | journal = Frontiers in Psychiatry | volume = 11 | article-number = 546796 | date = 2020 | pmid = 33024436 | pmc = 7516264 | doi = 10.3389/fpsyt.2020.546796 | doi-access = free | title-link = doi }}</ref><ref name="pmid32927246"/>

==History==
Modafinil was developed in France by [[neurophysiology]] professor [[Michel Jouvet]] and Lafon Laboratories. It is part of a series of benzhydryl sulfinyl compounds, including [[adrafinil]], initially used as a treatment for narcolepsy in France in 1986.<ref name="Denis-2021" /> Modafinil, the primary metabolite of [[adrafinil]],<ref name="pmid19810941">{{cite journal | vauthors = Ballas CA, Kim D, Baldassano CF, Hoeh N | title = Modafinil: past, present and future | journal = Expert Review of Neurotherapeutics | volume = 2 | issue = 4 | pages = 449–457 | date = July 2002 | pmid = 19810941 | doi = 10.1586/14737175.2.4.449 | s2cid = 32939239 }}</ref> has been prescribed in France since 1994 under the name Modiodal,<ref name="Denis-2021" /> and in the United States since 1998 as Provigil.<ref name="Provigil FDA label" /> Unlike modafinil, adrafinil does not have FDA approval and was withdrawn from the French market in 2011.<ref name="DrugBank-Adrafinil">{{cite web | url=https://go.drugbank.com/drugs/DB08925 | title=Adrafinil | publisher=The Governors of the University of Alberta | date=May 14, 2021 | access-date=May 14, 2021 | archive-date=May 16, 2021 | archive-url=https://web.archive.org/web/20210516092402/https://go.drugbank.com/drugs/DB08925 | url-status=live }}</ref>

The FDA approved modafinil in 1998 for [[narcolepsy]] treatment, and later for [[shift work sleep disorder]] and [[obstructive sleep apnea]] in 2003.<ref name="Provigil FDA label" /><ref name="U.S. Food and Drug Administration (FDA)-2001">{{cite web | title=Drug Approval Package: Provigil (Modafinil) NDA# 20717 | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=September 10, 2001 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/020717A_Provigil.cfm | access-date=March 1, 2024 | archive-date=March 1, 2024 | archive-url=https://web.archive.org/web/20240301182513/https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/020717A_Provigil.cfm }}</ref><ref name="pmid22363762">{{cite journal | vauthors = Kesselheim AS, Myers JA, Solomon DH, Winkelmayer WC, Levin R, Avorn J | title = The prevalence and cost of unapproved uses of top-selling orphan drugs | journal = PLOS ONE | volume = 7 | issue = 2 | article-number = e31894 | date = February 2012 | pmid = 22363762 | pmc = 3283698 | doi = 10.1371/journal.pone.0031894 | veditors = Alessi-Severini S | doi-access = free | title-link = doi | bibcode = 2012PLoSO...731894K }}</ref> It was approved in the UK in December 2002. In the United States, modafinil is marketed by [[Cephalon (company)|Cephalon]],<ref name="thepharmaletter-1995">{{cite web | url=https://www.thepharmaletter.com/article/cephalon-modafinil | title=Cephalon: Modafinil – Pharmaceutical industry news | date=October 8, 1995 | work=The Pharma Letter | access-date=November 15, 2023 | archive-date=November 15, 2023 | archive-url=https://web.archive.org/web/20231115191229/https://www.thepharmaletter.com/article/cephalon-modafinil | url-status=live }}</ref> who acquired the rights from Lafon and purchased the company in 2001.<ref name="thepharmaletter-1995"/>

Cephalon introduced armodafinil, the (''R'')-enantiomer of modafinil, in the United States in 2007. Generic versions of modafinil became available in the US in 2012 after extensive patent litigation.<ref name="pmid24773330">{{cite journal | vauthors = Gellad WF, Choi P, Mizah M, Good CB, Kesselheim AS | title = Assessing the chiral switch: approval and use of single-enantiomer drugs, 2001 to 2011 | journal = The American Journal of Managed Care | volume = 20 | issue = 3 | pages = e90–e97 | date = March 2014 | pmid = 24773330 }}</ref><ref name="generic-provigil">{{cite web | url=https://www.drugs.com/availability/generic-provigil.html | title=Generic Provigil Availability | publisher=[[Drugs.com]] | date=November 2023 | access-date=November 15, 2023 | archive-date=November 15, 2023 | archive-url=https://web.archive.org/web/20231115191917/https://www.drugs.com/availability/generic-provigil.html | url-status=live }}</ref>

==Society and culture==
Modafinil is not approved for use by children in multiple jurisdictions.<ref name="Modavigil PI" /><ref name="Product monograph including patient medication information Alertec modafinil tablets-100mg-2024">{{Cite web |url=https://pdf.hres.ca/dpd_pm/00071543.PDF |title=Product monograph including patient medication information Alertec modafinil tablets, 100 mg, oral mfr. std. central nervous system stimulant |access-date=February 28, 2024 |archive-date=February 21, 2024 |archive-url=https://web.archive.org/web/20240221143222/https://pdf.hres.ca/dpd_pm/00071543.PDF |url-status=live }}</ref><ref name="Modafinil Provigil SmPC" /><ref name="Provigil FDA label" /><ref name="European Medicines Agency-2010">{{cite web | title=Modafinil | website=European Medicines Agency | date=November 18, 2010 | url=https://www.ema.europa.eu/en/medicines/human/referrals/modafinil | access-date=February 28, 2024 | archive-date=January 20, 2024 | archive-url=https://web.archive.org/web/20240120112003/https://www.ema.europa.eu/en/medicines/human/referrals/modafinil | url-status=live }}</ref>

===Legal status===
==== Australia ====
In Australia, modafinil is considered to be a [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 4: Prescription Only Medicine|Schedule 4]] [[prescription-only medicine]]. This means that it is a drug with a perceived low potential for abuse and low risk of dependence; still, the use of Schedule 4 drugs in Australia is restricted to those who have a valid prescription from a medical practitioner; import from abroad is illegal.<ref name="Legislation.gov.au">{{cite web |title=Poisons Standard March 2018 |date=February 28, 2018 |url=https://www.legislation.gov.au/Details/F2018L00168 |access-date=January 20, 2019 |publisher=Legislation.gov.au |archive-date=August 7, 2020 |archive-url=https://web.archive.org/web/20200807113733/https://www.legislation.gov.au/Details/F2018L00168 |url-status=live }}</ref>

==== Canada ====
In Canada, modafinil is not specifically included in the lists of controlled drugs and substances specified within the [[Controlled Drugs and Substances Act]].<ref name="Canada-Gazette-2005">{{cite news|date=March 26, 2005 |title=Regulations Amending the Food and Drug Regulations (1184 — Modafinil) |newspaper=[[Canada Gazette]] |volume=140 |issue=20 |url=http://gazette.gc.ca/archives/p1/2005/2005-03-26/html/reg5-eng.html |archive-url=https://web.archive.org/web/20110706181716/http://gazette.gc.ca/archives/p1/2005/2005-03-26/html/reg5-eng.html |archive-date=July 6, 2011}}</ref> However, it is classified as a Schedule&nbsp;F prescription drug.<ref name="canada-modafinil-guidance">{{Cite web|url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/guidance-document.html|title=Guidance Document: Determining Prescription Status for Human and Veterinary Drugs| author = Health Canada|date=May 29, 2013|website=www.canada.ca|access-date=February 8, 2024|archive-date=February 8, 2024|archive-url=https://web.archive.org/web/20240208124250/https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/guidance-document.html|url-status=live}}</ref><ref name="canada-prescription-drug-list">{{Cite web|url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list.html|title=The Prescription Drug List| author = Health Canada|date=May 29, 2013|website=www.canada.ca|access-date=February 8, 2024|archive-date=June 28, 2023|archive-url=https://web.archive.org/web/20230628231029/https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list.html|url-status=live}}</ref><ref name="modafinil-canada-ca">{{Cite web|url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/questions-answers.html|title=Questions and Answers - Prescription Drug List| author = Health Canada|date=May 30, 2013|website=www.canada.ca|access-date=February 8, 2024|archive-date=February 8, 2024|archive-url=https://web.archive.org/web/20240208124251/https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/questions-answers.html|url-status=live}}</ref> This means that modafinil can only be obtained legally with a valid prescription from a licensed health care practitioner in Canada, and the import of modafinil to Canada from other countries is subject to restrictions: importing prescription drugs without an import permit may result in the seizure of the drugs at the border, the refusal of entry of the drugs into Canada, or prosecution.<ref name="import-of-modafinil-to-canada">{{cite web | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/importation-exportation/personal-use-health-products-guidance/document.html | title=Bringing health products into Canada for personal use (GUI-0116) | date=December 23, 2020 | access-date=January 29, 2024 | archive-date=January 29, 2024 | archive-url=https://web.archive.org/web/20240129173522/https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/importation-exportation/personal-use-health-products-guidance/document.html | url-status=live }}</ref>

====China====
In mainland China, modafinil is strictly controlled like other stimulants such as amphetamines and [[methylphenidate]]. It is classified as Class&nbsp;I psychotropic drug. This classification means that modafinil is considered to have a high potential for abuse and dependence, and is therefore subject to strict regulation and control. As a result, modafinil is only available by prescription and cannot be purchased over the counter. In order to obtain a prescription for modafinil, a patient must have a valid medical reason for using the drug, such as [[narcolepsy]] or [[obstructive sleep apnea]]. Additionally, the prescription must be written by a licensed physician and filled at a [[Pharmacy in China|licensed pharmacy]]. The use of modafinil for non-medical purposes, such as with the aim to improve cognitive performance or to stay awake for long periods of time, is strictly prohibited and can result in legal consequences.<ref name="China Food and Drug Administration">{{cite web|title=食品药品监管总局 公安部 国家卫生计生委关于公布麻醉药品和精神药品品种目录的通知 | trans-title = Notice from the Food and Drug Administration, the Ministry of Public Security, and the National Health and Family Planning Commission on publishing the catalog of narcotic drugs and psychotropic drugs | language = zh |publisher=China Food and Drug Administration|url=http://samr.cfda.gov.cn/WS01/CL0844/94735.html |archive-url=https://web.archive.org/web/20181205061404/http://samr.cfda.gov.cn/WS01/CL0844/94735.html|archive-date=December 5, 2018}}</ref><ref name="China-Modafinil">{{cite web|url=http://www.gov.cn/flfg/2007-03/13/content_549406.htm|title=处方管理办法(原卫生部令第53号)| trans-title = Prescription Management Measures (Former Ministry of Health Order No. 53) |website=中国政府网 (China Government Network) |language=zh|access-date=February 8, 2019|archive-date=February 8, 2020|archive-url=https://web.archive.org/web/20200208155424/http://www.gov.cn/flfg/2007-03/13/content_549406.htm|url-status=live}}</ref>

==== Europe ====
In Denmark, modafinil is a prescription drug but not listed as a controlled substance. According to the [[Danish Medicines Agency]], modafinil is approved for use in the treatment of narcolepsy; still, importing modafinil to Denmark is considered illegal without a valid prescription.<ref name="Retsinformation.dk-2020">{{cite web |url=https://www.retsinformation.dk/eli/lta/2020/950 |title=Bekendtgørelse om euforiserende stoffer |date=June 23, 2020 |website=Retsinformation.dk |language=da |trans-title=Narcotics act |access-date=October 7, 2020 |archive-date=November 28, 2020 |archive-url=https://web.archive.org/web/20201128175558/https://www.retsinformation.dk/eli/lta/2020/950 |url-status=live }}</ref><ref name="import-dk-1">{{cite web | url=https://laegemiddelstyrelsen.dk/en/pharmacies/medicines-imported-from-abroad/medicines-for-human-use/are-you-bringing-medicine-into-denmark/ | title=Are you bringing medicine into Denmark? | date=August 13, 2018 | access-date=February 5, 2024 | publisher=Danish Medicines Agency | archive-date=January 26, 2024 | archive-url=https://web.archive.org/web/20240126183328/https://laegemiddelstyrelsen.dk/en/pharmacies/medicines-imported-from-abroad/medicines-for-human-use/are-you-bringing-medicine-into-denmark/ | url-status=live }}</ref><ref name="import-dk-2">{{cite web | url=https://laegemiddelstyrelsen.dk/en/pharmacies/medicines-imported-from-abroad/ | title=Medicines imported from abroad | date=March 16, 2022 | access-date=February 5, 2024 | publisher=Danish Medicines Agency | archive-date=January 26, 2024 | archive-url=https://web.archive.org/web/20240126183315/https://laegemiddelstyrelsen.dk/en/pharmacies/medicines-imported-from-abroad/ | url-status=live }}</ref><ref name="Civilstyrelsen-2011">{{cite web|url=https://www.retsinformation.dk/eli/lta/2011/557|title=BEK nr 557 af 31/05/2011, Indenrigs- og Sundhedsministeriet|date=May 31, 2011|access-date=February 5, 2024|publisher=Civilstyrelsen|archive-date=January 26, 2024|archive-url=https://web.archive.org/web/20240126183312/https://www.retsinformation.dk/eli/lta/2011/557|url-status=live}}</ref>

'''Finland'''

In Finland, modafinil is a prescription drug but not listed as a [[controlled substance]]. Finland is a member of the European Union, and it is illegal to import prescription medicine from outside the European Union unless the person has a valid prescription.<ref name="Finlex.fi-2009">{{cite web|url=https://www.finlex.fi/fi/lainsaadanto/saadoskokoelma/2009/1095|title=Lääkealan turvallisuus- ja kehittämiskeskuksen päätöslääkeluettelosta|date=2009|website=Finlex.fi|access-date=January 3, 2017|archive-date=August 23, 2020|archive-url=https://web.archive.org/web/20200823111409/https://finlex.fi/fi/laki/alkup/2009/20091095|url-status=live}}</ref><ref name="finland-prohibited-goods">{{cite web|url=https://tulli.fi/en/private-persons/ordering-goods-online/prohibited-goods|title=Prohibited goods|publisher=Finnish Customs|access-date=February 5, 2024|archive-date=January 26, 2024|archive-url=https://web.archive.org/web/20240126183313/https://tulli.fi/en/private-persons/ordering-goods-online/prohibited-goods|url-status=live}}</ref><ref name="finland-doping">{{cite web|url=https://dopinglinkki.fi/en/info-bank/doping-substances/modafinil/|title=Modafinil|date=September 19, 2019|access-date=February 5, 2024|website=Dopinglinkki|publisher=A-klinikkasäätiö|archive-date=January 26, 2024|archive-url=https://web.archive.org/web/20240126183315/https://dopinglinkki.fi/en/info-bank/doping-substances/modafinil/|url-status=live}}</ref>

==== Republic of Moldova ====
In the Republic of Moldova, modafinil is classified as a psychotropic drug (included in table III list 3 which is the list of psychotropic substances as defined by the [[Government of Moldova]])<ref name="moldova_HG_list_of_substances"/> and is available by prescription.<ref name="moldova_HG_list_of_substances">{{cite web | url = https://www.legis.md/cautare/getResults?doc_id=103676&lang=ro | title = Hotărâre Nr. 79 din 23-01-2006 privind aprobarea Listei substanţelor stupefiante, psihotrope şi a plantelor care conţin astfel de substanţe depistate în trafic ilicit, precum şi cantităţile acestora | trans-title = Decision No. 79 of 01-23-2006 regarding the approval of the List of narcotic, psychotropic substances and plants containing such substances detected in illicit traffic, as well as their quantities | language = Romanian | publisher = Moldavian Ministry of Justice | date = January 23, 2006 | access-date = February 5, 2024 | archive-date = April 3, 2023 | archive-url = https://web.archive.org/web/20230403194451/https://www.legis.md/cautare/getResults?doc_id=103676&lang=ro | url-status = live }}</ref> Importation of modafinil may be considered illegal and subject to severe penalties, even if you have a prescription.<ref name="Customs-Moldova-2023">{{cite web | url = https://customs.gov.md/ro/articles/e-bine-sa-stim-1369-ro | title = Serviciul Vamal al Republicii Moldova – E bine să știm! | trans-title = Customs Service of the Republic of Moldova - Good to know! | language = Romanian | work = Customs Service of the Republic of Moldova | access-date = September 4, 2023 | archive-date = September 4, 2023 | archive-url = https://web.archive.org/web/20230904105420/https://customs.gov.md/ro/articles/e-bine-sa-stim-1369-ro | url-status = live }}</ref> For example, on June 29, 2017, [[Poșta Moldovei|Moldovan postal officers]] discovered 60 tablets of Modalert (200&nbsp;mg modafinil tablets) in a parcel sent from India to a resident in [[Chișinău]], Moldova. The prohibited substance was detected during a routine scan and was seized as illegal. The authorities were notified of the incident and the recipient was charged with criminal penalties.<ref name="modafinil-moldova-2017-discovered-curentul-md">{{cite web|date=June 30, 2007|publisher=curentul.md|vauthors=Parfeni C|url=http://curentul.md/stiri/substante-psihotrope-si-un-pumnal-militar-au-fost-depistate-de-vamesi-in-coletele-postale.html|title=Substanțe psihotrope și un pumnal militar au fost depistate de vameși în coletele poștale|access-date=January 29, 2024|archive-date=January 29, 2024|archive-url=https://web.archive.org/web/20240129202533/http://curentul.md/stiri/substante-psihotrope-si-un-pumnal-militar-au-fost-depistate-de-vamesi-in-coletele-postale.html|url-status=live}}</ref><ref name="modafinil-moldova-2017-discovered-noi-md">{{cite web| publisher=noi.md| date=June 30, 2017| url=https://noi.md/md/news_id/231399| title=Centrul de Sănătate din Edineţ va fi eficientizat energetic| access-date=January 29, 2024| archive-date=January 29, 2024| archive-url=https://web.archive.org/web/20240129202534/https://noi.md/md/news_id/231399| url-status=live}}</ref> In the [[Transnistria]] region of Moldova, modafinil is completely prohibited, due to application of the legislation similar to that of Russia where modafinil is completely prohibited and is in the same list as narcotics. Possession or an attempt to bring modafinil to Transnistria potentially leads to imprisonment.<ref name="base.consultant.ru-2017" />

==== Romania ====
In Romania, modafinil is classified as a stimulant doping agent and is prohibited in sports competitions.<ref name="ro-antidopink">{{cite web | title = LISTA INTERZISĂ - 2018 | trans-title = Forbidden List - 2018 |work =AGENȚIA NAȚIONALĂ ANTI-DOPING | trans-work = National Anti-Doping Agency | language = Romanian |url=http://anad.gov.ro/web/wp-content/uploads/2017/10/LISTA-2018-web.pdf |archive-date=February 24, 2021 |archive-url=https://web.archive.org/web/20210224105716/http://anad.gov.ro/web/wp-content/uploads/2017/10/LISTA-2018-web.pdf }}</ref> In 2022, laws were passed making its importation or sale a felony, punishable by three to seven years in jail.<ref name="LEGE 219 26/07/2021 – Portal Legislativ">{{cite web | url=https://legislatie.just.ro/Public/DetaliiDocumentAfis/245003 | title=LEGE 219 26/07/2021 | trans-title = Law 219 26/07/2021 - | work = Portal Legislativ | trans-work = Romanian Legislative Portal| access-date=October 16, 2022 | archive-date=October 16, 2022 | archive-url=https://web.archive.org/web/20221016104753/https://legislatie.just.ro/Public/DetaliiDocumentAfis/245003 | url-status=live | language = Romanian }}</ref> Simple possession for personal use may result in a fine and confiscation.<ref name="LEGE 219 26/07/2021 – Portal Legislativ" />

==== Sweden ====
In Sweden, modafinil is classified as a schedule&nbsp;IV substance, which means that it is considered to have a low potential for abuse and a low risk of dependence. Still, possession is illegal without a prescription.<ref name="LVFS">{{cite web |title=Läkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika | trans-title = The Swedish Medicines Agency's regulations (LVFS 2011: 10) on lists of drugs | language = sv |url=https://lakemedelsverket.se/upload/lvfs/konsoliderade/LVFS_2011_10_konsoliderad_tom_HSLF-FS_2019_7.pdf |archive-url=https://web.archive.org/web/20190807175859/https://lakemedelsverket.se/upload/lvfs/konsoliderade/LVFS_2011_10_konsoliderad_tom_HSLF-FS_2019_7.pdf |archive-date=August 7, 2019 }}</ref>

==== United Kingdom ====
In the United Kingdom, it is not listed in [[Misuse of Drugs Act 1971|Misuse of Drugs Act]], so possession is not illegal, but a prescription is required.<ref name="MHRA-2013">{{cite web|url = http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con273748.pdf|title = MHRA license for Modafinil in UK|author = MHRA|date = April 3, 2013|publisher = MHRA|location = London|access-date = April 3, 2013|archive-date = January 22, 2016|archive-url = https://web.archive.org/web/20160122195257/http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con273748.pdf|url-status = live}}</ref>

====Mexico====
In Mexico, modafinil is not listed as a controlled substance, in the National Health Law, and can be purchased in pharmacies without prescription.<ref name="Federal Commission for Protection against Health Risks-2007">{{cite web |title=Estupefacientes y Psicotrópicos |trans-title=Narcotic Drugs and Psychotropic Substances |language=es |publisher=<! --Comisión Federal para la Protección contra Riesgos Sanitarios -->Federal Commission for Protection against Health Risks |url=http://www.cofepris.gob.mx/pyp/estpsic/es.htm |archive-url=https://web.archive.org/web/20070713135452/http://www.cofepris.gob.mx/pyp/estpsic/es.htm |archive-date=July 13, 2007}}</ref>

====Japan====
In Japan, modafinil is Schedule&nbsp;I psychotropic drug. This means that it is considered to have a high potential for abuse and dependence, and is therefore subject to strict regulations. The use of Schedule I drugs in Japan is generally prohibited, except under certain circumstances, such as for medical purposes. It can only be prescribed by a doctor. It cannot be imported or exported without a permit. It cannot be used while driving or operating machinery.<ref name="List of psychotropics">{{cite web|url=http://www.ncd.mhlw.go.jp/img/en/total.pdf|title=List of psychotropics|access-date=May 24, 2019|archive-date=July 11, 2019|archive-url=https://web.archive.org/web/20190711014332/http://www.ncd.mhlw.go.jp/img/en/total.pdf| work = Narcotics Control Department }}</ref><ref name="Japan-Modafinil">{{cite web |url=http://www.fukushihoken.metro.tokyo.jp/kenkou/iyaku/sonota/shitei_m/moda.html |title=モダフィニルの向精神薬への指定 | trans-title = Designation as a psychotropic drug of Modafinyl | language = Japanese |access-date=January 17, 2017 |archive-url=https://web.archive.org/web/20150515002556/http://www.fukushihoken.metro.tokyo.jp/kenkou/iyaku/sonota/shitei_m/moda.html |archive-date=May 15, 2015 }}</ref> [[Cephalon (company)|Cephalon]] licensed Alfresa Corporation to produce, and [[Mitsubishi Tanabe Pharma]] to sell modafinil products under the trade name Modiodal in Japan.<ref name="modafinil-japanese">{{cite web|title=医疗用医薬品の添付文书情报-モディオダール锭100mg | trans-title = Attachment of drugs for doctors-Modio Dal 100mg |work = 独立行政法人 医薬品医疗机器総合机 | trans-work = Pharmaceuticals and Medical Devices Agency |url=http://www.info.pmda.go.jp/go/pack/1179047F1022_2_15/ |language=ja|archive-url=https://web.archive.org/web/20190209124042/http://www.info.pmda.go.jp/go/pack/1179047F1022_2_15/|archive-date=February 9, 2019}}</ref> There have been arrests of people who imported modafinil for personal use.<ref name="Medicallaw.exblog.jp">{{cite web|url=https://medicallaw.exblog.jp/20422896/|title=モダフィニル密輸で逮捕された歯科医師, ダイエットに使用と供述(報道)| trans-title = Dentist who was arrested for Modafinyl smuggling, usage and confidence (report) | language = ja |website=Medicallaw.exblog.jp|access-date=January 20, 2019|archive-url=https://web.archive.org/web/20190121010916/https://medicallaw.exblog.jp/20422896/|archive-date=January 21, 2019}}</ref><ref name="Hayabusa3.5ch.net">{{cite web|url=https://hayabusa3.5ch.net/test/read.cgi/news/1391949369/|title=向精神薬をインドから密輸入した男を逮捕 | trans-title = Arrested a man who imported psychotropic drugs from India | language = ja |website=Hayabusa3.5ch.net |access-date=January 20, 2019|archive-date=January 21, 2019|archive-url =https://web.archive.org/web/20190121064119/https://hayabusa3.5ch.net/test/read.cgi/news/1391949369/ |url-status=live}}</ref>

====Russia====
In Russia, starting from May 18, 2012, modafinil is Schedule&nbsp;II controlled substance. Being classified as a Schedule II controlled substance in Russia means that it is seen as a drug with a high potential for abuse and dependence. This classification imposes strict regulations on the production, distribution, and use of modafinil. Possession of a few modafinil pills can lead to three to ten years imprisonment. Modafinil is not approved for medical use in Russia and cannot be bought even in pharmacies. It also cannot be imported from abroad, even if you have a prescription issued outside Russia.<ref name="base.consultant.ru-2017">{{cite web |url=http://base.consultant.ru/cons/cgi/online.cgi?req=doc;base=LAW;n=142882;fld=134;dst=4294967295;rnd=0.8965571122244;from=141820-563 |title=Decree of the Government of the Russian Federation of 06.30.1998 N 681 (as amended on 02.26.2013) "On approval of the list of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation" |website=base.consultant.ru |format=PDF |access-date=January 3, 2017 |archive-date=August 28, 2021 |archive-url=https://web.archive.org/web/20210828174157/http://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=142882&fld=134&dst=4294967295&rnd=0.8965571122244&from=141820-563 |url-status=live | language = Russian }}</ref><ref name="Russia-New-Stimulator">{{cite web |title=Россия начнет производить новый стимулятор на базе модафинила |trans-title=Russia will begin to produce a new stimulator based on modafinil |language=ru |url=https://medvestnik.ru/content/news/Rossiya-gotovitsya-proizvodit-novyi-stimulyator-na-baze-modafinila.html |access-date=December 8, 2023 |website=medvestnik.ru |archive-date=December 8, 2023 |archive-url=https://web.archive.org/web/20231208054906/https://medvestnik.ru/content/news/Rossiya-gotovitsya-proizvodit-novyi-stimulyator-na-baze-modafinila.html |url-status=live }}</ref> There are multiple cases of criminal proceedings initiated against Russian residents who tried to import modafinil by mail from abroad.<ref name="SpbPenal2020">{{cite web |date=February 19, 2020 |title=В Петербурге завели дело из-за полученных по почте таблеток от сонливости |trans-title=In St. Petersburg, a case was started because of the pills received by mail from drowsiness |language=ru |url=https://www.rbc.ru/society/19/02/2020/5e4d28499a79473eeeac6613 |access-date=December 8, 2023 |website=РБК (RBC) |archive-date=December 8, 2023 |archive-url=https://web.archive.org/web/20231208054905/https://www.rbc.ru/society/19/02/2020/5e4d28499a79473eeeac6613 |url-status=live }}</ref><ref name="ru-russian-trapped-2023">{{cite web |date=October 11, 2023 |title="Вместо лечения — тюрьма". Россияне с редкими болезнями оказались в ловушке |trans-title="Instead of treatment - a prison." Russians with rare diseases were trapped |url=https://ria.ru/20231011/son-1901816843.html |access-date=December 8, 2023 |website=РИА Новости (Ria News) |language=ru |archive-date=December 8, 2023 |archive-url=https://web.archive.org/web/20231208054905/https://ria.ru/20231011/son-1901816843.html |url-status=live }}</ref>

====South Africa====
In South Africa, modafinil is Schedule&nbsp;V substance, which means that it is legal to use modafinil in South Africa, but only with a valid prescription from a licensed medical practitioner.<ref name="SAFLII-2003">{{cite web|title = GENERAL REGULATIONS MADE IN TERMS OF THE MEDICINES AND RELATED SUBSTANCES ACT 101 OF 1965, AS AMENDED Government Notice R510 in Government Gazette 24727 dated 10 April 2003. 22A/16/b; states that although import and export is restricted, possession is not illegal providing that a prescription is present.|author = SA Government|date = April 10, 2003|publisher = SAFLII|location = Pretoria| url=http://saflii.org/za/legis/consol_reg/marsa101o1965rangnr510723.pdf |archive-url = https://web.archive.org/web/20160422183746/http://saflii.org/za/legis/consol_reg/marsa101o1965rangnr510723.pdf|archive-date = April 22, 2016}}</ref>

====United States====
In the United States, modafinil is classified as a [[Controlled Substances Act#Schedule IV|schedule IV controlled substance]]<ref name="modafinil-schedule-IV-1999"/> under US federal law.<ref name="Provigil FDA label" /><ref name="Pharmaceutical Press-2017">{{cite book |title=BNF 74 |date=September 2017 |publisher=Pharmaceutical Press |isbn=978-0-85711-298-9 |page=468 |edition=74}}</ref> This means that the drug has a low potential for abuse and dependence compared to other controlled substances. However, it still requires a prescription from a [[Health care provider|licensed healthcare provider]] to obtain.<ref name="Pharmaceutical Press-2017"/>

It is illegal to import modafinil to the United States without a [[Drug Enforcement Administration]] ([[Drug Enforcement Administration|DEA]])–registered importer and a prescription.<ref name="United States Drug Enforcement Administration-info-modafinil-2007">{{Cite web |title=Is It Illegal to Obtain Controlled Substances from the Internet? |url=http://www.usdoj.gov/dea/illegal_internet.html |archive-url=https://web.archive.org/web/20070709032821/http://www.usdoj.gov/dea/illegal_internet.html |archive-date=July 9, 2007 |publisher=[[United States Drug Enforcement Administration]] |access-date=July 21, 2007}}</ref> Individuals may legally bring modafinil into the US from a foreign country for personal use, limited to 50 dosage units, with a prescription and proper declaration at the border.<ref name="United States Department of Justice-1997">{{cite web |date=March 24, 1997 |title=USC 201 Section 1301.26 Exemptions from import or export requirements for personal medical use |archive-url=https://web.archive.org/web/20070203125143/http://www.deadiversion.usdoj.gov/21cfr/cfr/1301/1301_26.htm |archive-date=February 3, 2007 |access-date=January 10, 2007 |publisher=[[United States Department of Justice]]|url=http://www.deadiversion.usdoj.gov/21cfr/cfr/1301/1301_26.htm }}</ref> Under the [[Pure Food and Drug Act]], marketing drugs for off-label uses is prohibited.<ref name="FDA-DMA-1987">{{cite web |title=Prescription Drug Marketing Act of 1987 (PDMA), PL 100-293 |archive-url=https://web.archive.org/web/20080223233036/https://www.fda.gov/opacom/laws/pdma.html |archive-date=February 23, 2008 |publisher=U.S. [[Food and Drug Administration]] (FDA) |url=https://www.fda.gov/opacom/laws/pdma.html }}</ref> Cephalon, the manufacturer of Provigil, faced legal issues for promoting off-label uses and paid significant fines in 2008.<ref name="Allison-2009">{{cite web |vauthors=Allison J |date=October 9, 2009 |title=Class Action Over Cephalon Off-Label Claims Tossed |url=https://www.law360.com/articles/127434 |publisher=Law360 |quote=Cephalon executives have repeatedly said that they do not condone off-label use of Provigil, but in 2002 the company was reprimanded by the FDA for distributing marketing materials that presented the drug as a remedy for tiredness, "decreased activity" and other supposed ailments. In 2008, Cephalon paid $425m and pleaded guilty to a federal criminal charge relating to its promotion of off-label uses for Provigil and two other drugs. |access-date=January 12, 2022 |archive-date=April 30, 2022 |archive-url=https://web.archive.org/web/20220430201243/https://www.law360.com/articles/127434 |url-status=live }}</ref>

===Brand names===
[[File:Modafinil-generic-aspendos.jpg|thumb|right|A [[Generic drug|generic]] formulation of modafinil marketed under the Aspendos brand name]]
Modafinil is sold under a variety of brand names worldwide, including Alertec, Alertex, Altasomil, Aspendos, Bravamax, Forcilin, Intensit, Karim, Mentix, Modafinilo, Modalert, Modanil, Modasomil, Modvigil, Modiodal, Modiwake, Movigil, Provigil, Resotyl, Stavigile, Vigia, Vigicer, Vigil, Vigimax, Waklert, and Zalux.<ref name="Drugs.com-International-Brands-2017">{{cite web|title=Modafinil – International Brands|url=https://www.drugs.com/international/modafinil.html|publisher=Drugs.com|access-date=January 8, 2017|archive-date=July 18, 2020|archive-url=https://web.archive.org/web/20200718040144/https://www.drugs.com/international/modafinil.html|url-status=live}}</ref>

===Economics===
Originally developed in the 1970s by French neuroscientist Michel Jouvet and Lafon Laboratories, modafinil has been prescribed in France since 1994,<ref name="Denis-2021">{{cite journal|vauthors=Denis F|date=2021|title=Smart drugs et nootropiques|journal=Socio-anthropologie|issue=43|pages=97–110|doi=10.4000/socio-anthropologie.8393|s2cid=237863162|issn=1276-8707|doi-access=free|title-link=doi|volume=43 |url=https://halshs.archives-ouvertes.fr/halshs-03264161/file/DENIS_F%C3%A9lix_2021.pdf|access-date=February 2, 2024|archive-date=January 8, 2022|archive-url=https://web.archive.org/web/20220108000038/https://halshs.archives-ouvertes.fr/halshs-03264161/file/DENIS_F%C3%A9lix_2021.pdf|url-status=live}}</ref><ref name="pmid37839272"/> and was approved for medical use in the United States in 1998.<ref name="Provigil FDA label" /><ref name="pmid37839272"/>

<!-- Please see [[Talk:Modafinil#Citation after each sentence in Society and culture/economy section]] before adding/removing sources and asking for sources in the following paragraph]] -->
Concerns have been raised about the growing use of modafinil as a "smart drug" or cognitive enhancer among healthy individuals who use it with the aim to improve concentration and memory.<ref name="O'Connor-2004"/><ref name="Petrounin-2014"/> In 2003, modafinil sales were skyrocketing, with some experts concerned that it had become a tempting pick-me-up for people looking for an extra edge in a productivity-obsessed society.<ref name="O'Connor-2004"/> The cost of modafinil varied depending on factors such as location and insurance coverage;<ref name="O'Connor-2004" /><ref name="Petrounin-2014" /><ref name="Kanter-2013" /> still, in 2004, the price of modafinil in the US was around $120 or more per monthly supply.<ref name="O'Connor-2004" /> However, the availability of generic versions has increased since then and may have driven down prices.<ref name="O'Connor-2004">{{cite news |url=https://www.nytimes.com/2004/06/29/health/wakefulness-finds-a-powerful-ally.html |title=Wakefulness Finds a Powerful Ally|vauthors=O'Connor A|work=[[The New York Times]]|date=June 29, 2004 |access-date=December 2, 2023 |archive-date=December 2, 2023 |archive-url=https://web.archive.org/web/20231202005726/https://www.nytimes.com/2004/06/29/health/wakefulness-finds-a-powerful-ally.html|url-status=live}}</ref><ref name="Petrounin-2014">{{cite news |url=https://www.nytimes.com/2014/07/07/world/europe/european-students-use-of-smart-drugs-is-said-to-rise.html |title=European Students' Use of 'Smart Drugs' is Said to Rise |work=[[The New York Times]] |date=July 6, 2014 |vauthors=Petrounin D |access-date=December 2, 2023 |archive-date=December 2, 2023 |archive-url=https://web.archive.org/web/20231202005728/https://www.nytimes.com/2014/07/07/world/europe/european-students-use-of-smart-drugs-is-said-to-rise.html |url-status=live }}</ref><ref name="Kanter-2013">{{cite news |url=https://www.nytimes.com/2013/06/20/business/global/eu-fines-drug-companies-for-delaying-generics.html |title=Europe Fines Drug Companies for Delaying Generics |work=[[The New York Times]] |date=June 19, 2013 |vauthors=Kanter J |access-date=December 2, 2023 |archive-date=December 2, 2023 |archive-url=https://web.archive.org/web/20231202005731/https://www.nytimes.com/2013/06/20/business/global/eu-fines-drug-companies-for-delaying-generics.html |url-status=live }}</ref>

In 2020, modafinil was the 302nd most commonly prescribed medication in the United States, with just over 1,000,000 prescriptions.<ref name="Modafinil - Drug Usage Statistics">{{cite web | title = Modafinil – Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Modafinil | access-date = October 7, 2022 | archive-date = June 6, 2023 | archive-url = https://web.archive.org/web/20230606002027/https://clincalc.com/DrugStats/Drugs/Modafinil | url-status = live }}</ref>

{{As of|2024|post=,}} the global sales figures for modafinil are not known. Still, modafinil sold under the brand name Provigil accounted for over 40% of [[Cephalon (company)|Cephalon]]'s global turnover for several years, according to the information published in 2020.<ref name="Pay-For-Delay - EC fines">{{cite news | url=https://www.cuatrecasas.com/en/global/art/pay-for-delay-ec-fines-teva-cephalon-delaying-entry-generic-version-modafinil-market | title='Pay-For-Delay': The EC fines Teva and Cephalon for delaying the market entry of a generic version of Modafinil | newspaper=Cuatrecasas | access-date=November 16, 2023 | archive-date=November 16, 2023 | archive-url=https://web.archive.org/web/20231116214034/https://www.cuatrecasas.com/en/global/art/pay-for-delay-ec-fines-teva-cephalon-delaying-entry-generic-version-modafinil-market | url-status=live }}</ref>

===Patent protection and litigation===
Modafinil's patent history involves several key developments. The original patent, {{US patent|4927855}}, was granted to Laboratoire L. Lafon in 1990, covering the chemical compound of modafinil. This patent expired in 2010.<ref name="patent4927855">{{cite patent|number=4927855|country=US}}</ref> In 1994, Cephalon filed a patent for modafinil in the form of particles of a defined size, represented by {{US patent|5618845}}, which expired in 2015.<ref name="www.bizjournals.com-2006">{{cite magazine|url=http://www.bizjournals.com/philadelphia/stories/2006/03/27/daily13.html |title=Cephalon gets six-month Provigil patent extension |magazine=Philadelphia Business Journal |date=March 28, 2006 |access-date=July 21, 2007 |archive-date=August 4, 2008 |archive-url=https://web.archive.org/web/20080804204005/http://www.bizjournals.com/philadelphia/stories/2006/03/27/daily13.html |url-status=live }}</ref>

Following the nearing expiration of marketing rights in 2002, generic manufacturers, including Mylan and Teva, applied for FDA approval to market a generic form of modafinil, leading to legal challenges by Cephalon regarding the particle size patent.<ref name="Details for Patent RE37516">{{cite web |url=http://www.drugpatentwatch.com/ultimate/preview/patent/index.php?query=RE37516 |title=Details for Patent: RE37516 |access-date=November 29, 2009 |archive-date=January 1, 2014 |archive-url=https://web.archive.org/web/20140101192226/http://www.drugpatentwatch.com/ultimate/preview/patent/index.php?query=RE37516 |url-status=live }}</ref> The patent RE&nbsp;37,516 was declared invalid and unenforceable in 2011.<ref name="Justia-2010">{{cite web |url=http://law.justia.com/cases/federal/district-courts/pennsylvania/paedce/2:2006cv02768/205626/514 |title=Document 514 :: APOTEX, INC. v. CEPHALON, INC. et al |publisher=Pennsylvania Eastern District Court :: US Federal District Courts Cases :: Justia |date=October 31, 2010 |access-date=July 4, 2012 |archive-date=January 1, 2014 |archive-url=https://web.archive.org/web/20140101044356/http://law.justia.com/cases/federal/district-courts/pennsylvania/paedce/2:2006cv02768/205626/514 |url-status=live }}</ref>

In addition, Cephalon entered agreements with several generic drug manufacturers to delay the sale of generic modafinil in the US. These agreements were subject to legal scrutiny and antitrust investigations, culminating in a ruling by the Court of Appeals in 2016, which found that the settlements did not violate antitrust laws.<ref name="ModafinilCourtCaseInReAntitrust">{{cite court|court=Court of Appeals, 3rd Circuit|litigants=In re: Modafinil Antitrust Litigation|date=2016}}</ref>

===Sports===
The regulation of modafinil as a [[Doping in sport|doping agent]] has been controversial in the sporting world, with high-profile cases attracting press coverage since several prominent American athletes tested positive for the substance. Some athletes who used modafinil protested that the drug was not on the prohibited list at the time of their offenses.<ref name="The World Anti-Doping Code International Standard-2017">{{cite book | publisher = World Anti-Doping Agency |title=The World Anti-Doping Code: International Standard |chapter=Prohibited List 2018 |chapter-url=https://www.wada-ama.org/sites/default/files/prohibited_list_2018_en.pdf |url=https://www.wada-ama.org/en/content/what-is-prohibited |date=September 5, 2017 |access-date=January 12, 2022 |archive-date=July 3, 2021 |archive-url=https://web.archive.org/web/20210703232308/https://www.wada-ama.org/en/content/what-is-prohibited |url-status=live }}</ref> However, the [[World Anti-Doping Agency]] (WADA) maintains that modafinil was related to already-banned substances. The Agency added modafinil to its list of prohibited substances on August 3, 2004, ten days before the start of the [[2004 Summer Olympics]].<ref name="mdpi-advanced-mass-spectrometry">{{Cite journal|title=Citius, Altius, Fortius—Advanced Mass Spectrometry in Service of Forensic Analysis| vauthors = Grocholska P, Popiel D, Walter M, Biernat M, Cebrat M, Kuczer M, Modzel M, Bąchor R, Kluczyk A |date=August 2022 |journal=Chemosensors |volume=10 |issue=8 |page=324 |doi=10.3390/chemosensors10080324 |doi-access=free }}</ref>

Several athletes, such as sprinter [[Kelli White]] in 2003,<ref name="Nazzaro-2013">{{cite news |vauthors=Nazzaro MN |date=August 17, 2013 |title=Out of Track's Doping Scandal, Redemption and Progress |work=[[The New York Times]] |url=https://www.nytimes.com/2013/08/18/sports/olympics/out-of-a-doping-scandal-redemption-for-Kelli-White-and-progress-for-track.html |access-date=December 3, 2023 |issn=0362-4331 |archive-date=December 3, 2023 |archive-url=https://web.archive.org/web/20231203143118/https://www.nytimes.com/2013/08/18/sports/olympics/out-of-a-doping-scandal-redemption-for-Kelli-White-and-progress-for-track.html |url-status=live }}</ref> cyclist [[David Clinger]]<ref name="www.cyclingnews.com-2011">{{cite news |url=http://www.cyclingnews.com/news/clinger-given-lifetime-ban-for-second-doping-infraction |title=Clinger given lifetime ban for second doping infraction |publisher=Cycling News |date=August 14, 2011 |access-date=October 8, 2014 |archive-date=October 13, 2014 |archive-url=https://web.archive.org/web/20141013173114/http://www.cyclingnews.com/news/clinger-given-lifetime-ban-for-second-doping-infraction |url-status=live }}</ref> and basketball player [[Diana Taurasi]]<ref name="The Washington Post-2010">{{cite news |url=https://www.washingtonpost.com/wp-dyn/content/article/2010/12/24/AR2010122402993.html |newspaper=[[The Washington Post]] |title=Taurasi tested positive for modafinil |date=December 25, 2010 |access-date=December 31, 2013 |archive-date=October 6, 2014 |archive-url=https://web.archive.org/web/20141006091440/http://www.washingtonpost.com/wp-dyn/content/article/2010/12/24/AR2010122402993.html |url-status=live }}</ref> in 2010, and rower Timothy Grant in 2015,<ref name="The Guardian-2015">{{cite news|url=https://www.theguardian.com/sport/2015/nov/23/british-rowers-handed-two-year-bans-doping-violations-sybren-hoogland-timothy-grant|title=British rowers handed two-year bans for taking banned substances|date=November 23, 2015|newspaper=[[The Guardian]]|access-date=December 15, 2016|archive-date=July 9, 2020|archive-url=https://web.archive.org/web/20200709214752/https://www.theguardian.com/sport/2015/nov/23/british-rowers-handed-two-year-bans-doping-violations-sybren-hoogland-timothy-grant|url-status=live}}</ref> were accused of using modafinil as a performance-enhancing [[doping (sport)|doping]] agent. Taurasi and another player—Monique Coker, tested at the same lab—were later cleared.<ref name="Voepel-2011">{{cite web |url=https://www.espn.com/wnba/columns/story?columnist=voepel_mechelle&id=6135920 |vauthors=Voepel M |title=Taurasi: 'I've lost 3 months of my career' |date=February 18, 2011 |access-date=April 11, 2011 |archive-date=October 6, 2015 |archive-url=https://web.archive.org/web/20151006020737/http://sports.espn.go.com/wnba/columns/story?columnist=voepel_mechelle&id=6135920 |url-status=live }}</ref> Kelli White, who tested positive after her 100m victory at the 2003 World Championships in Paris, was stripped of her gold medals.<ref name="news.bbc.co.uk-2003">{{cite news|url=http://news.bbc.co.uk/sport2/hi/athletics/world_athletics_2003/3077070.stm|title=White guilty of doping|date=September 9, 2003|via=news.bbc.co.uk|access-date=November 15, 2023|archive-date=November 15, 2023|archive-url=https://web.archive.org/web/20231115164109/http://news.bbc.co.uk/sport2/hi/athletics/world_athletics_2003/3077070.stm|url-status=live}}</ref> She claimed that she used modafinil to treat narcolepsy, but the [[International Association of Athletics Federations]] (IAAF) ruled that modafinil was a performance-enhancing drug.<ref name="news.bbc.co.uk-2003"/>

The [[BALCO]] scandal brought to light an unsubstantiated (but widely published) account of Major League Baseball's all-time leading home-run hitter [[Barry Bonds]]' supplemental chemical regimen that included modafinil in addition to [[anabolic steroid]]s and [[human growth hormone]].<ref name="CBC-News-2006">{{cite news|title=Book alleges Bonds's drug use|work=CBC News|url=https://www.cbc.ca/sports/baseball/book-alleges-bonds-s-drug-use-1.605000|date=March 7, 2006|access-date=January 27, 2024|archive-date=January 27, 2024|archive-url=https://web.archive.org/web/20240127204646/https://www.cbc.ca/sports/baseball/book-alleges-bonds-s-drug-use-1.605000|url-status=live}}</ref>

===Social views===
The use of modafinil as a supposed cognitive enhancer may be considered as cheating, unnatural, or risky.<ref name="The rise of smart drugs-2016">{{cite web | vauthors=Macnaughton O | url=https://www.tatler.com/article/the-rise-of-smart-drugs | title=The rise of smart drugs | date=March 16, 2016 | work=Tatler | access-date=November 15, 2023 | archive-date=November 15, 2023 | archive-url=https://web.archive.org/web/20231115162141/https://www.tatler.com/article/the-rise-of-smart-drugs | url-status=live }}</ref> The [[University of Sussex]] explained that it is a prescription drug and the decision should be made by the [[Health professional|doctor]] on whether to prescribe modafinil to a student.<ref name="We asked Sussex University if Modafinil is cheating-2017">{{cite web | vauthors=Farrell K | url=https://thetab.com/uk/sussex/2017/11/06/asked-sussex-university-modafinil-cheating-22575 | title=We asked Sussex University if Modafinil is cheating | date=November 6, 2017 | work=The Sussex Tab | access-date=November 15, 2023 | archive-date=November 15, 2023 | archive-url=https://web.archive.org/web/20231115162143/https://thetab.com/uk/sussex/2017/11/06/asked-sussex-university-modafinil-cheating-22575 | url-status=live }}</ref> As a matter of [[bioethics]], the US [[President's Council on Bioethics]] argued that excellence achieved through the use of drugs like modafinil is "cheap" as it obviates the need for hard work and study, and is not fully authentic because the excellence is partly attributable to the drug, not the individual.<ref name="Porsdam Mann-2018">{{cite journal |doi=10.1080/17449642.2018.1443050 |title=Is the use of modafinil, a pharmacological cognitive enhancer, cheating? |date=2018 |vauthors=Porsdam Mann S, de Lora Deltoro P, Cochrane T, Mitchell C |journal=Ethics and Education |volume=13 |issue=2 |pages=251–267 |s2cid=149138516 |url=https://philpapers.org/archive/PORITU.pdf |access-date=February 2, 2024 |archive-date=February 2, 2024 |archive-url=https://web.archive.org/web/20240202114822/https://philpapers.org/archive/PORITU.pdf |url-status=live }}</ref> Alternately, people in environments like [[Wall street trader|Wall Street trading]] may not view the use of modafinil as cheating, believing that if modafinil can give them an edge and they are aware of the risks involved, it should not be considered as cheating.<ref name="Robert-2013">{{cite magazine|magazine=New York Magazine|url=https://nymag.com/news/intelligencer/modafinil-2013-4/|title=The Real Limitless Drug Isn't Just for Lifehackers Anymore|date=March 29, 2013| vauthors = Robert K |access-date=March 16, 2024|archive-date=December 26, 2023|archive-url=https://web.archive.org/web/20231226213829/https://nymag.com/news/intelligencer/modafinil-2013-4/|url-status=live}}</ref> Due to such varying views, modafinil users for narcolepsy may cope with stigma by hiding, denying, or justifying their use, or by seeking support from others who share their views or experiences.<ref name="pmid32023288">{{cite journal | vauthors = Teodorini RD, Rycroft N, Smith-Spark JH | title = The off-prescription use of modafinil: An online survey of perceived risks and benefits | journal = PLOS ONE | volume = 15 | issue = 2 | article-number = e0227818 | date = 2020 | pmid = 32023288 | pmc = 7001904 | doi = 10.1371/journal.pone.0227818 | doi-access = free | title-link = doi | bibcode = 2020PLoSO..1527818T }}</ref><ref name="pmid28179647">{{cite journal | vauthors = Kornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, Overeem S | title = Narcolepsy | journal = Nature Reviews. Disease Primers | volume = 3 | article-number = 16100 | date = February 2017 | pmid = 28179647 | doi = 10.1038/nrdp.2016.100 | s2cid = 266008273 | url = http://www.hal.inserm.fr/inserm-01484949/file/nrdp2016100_Primer_1486657828_1.pdf }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

==Research==
===Psychiatric conditions===
====Major depressive disorder====
Modafinil has been studied in the treatment of [[major depressive disorder]].<ref name="pmid28318897">{{cite journal | vauthors = Kleeblatt J, Betzler F, Kilarski LL, Bschor T, Köhler S | title = Efficacy of off-label augmentation in unipolar depression: A systematic review of the evidence | journal = European Neuropsychopharmacology | volume = 27 | issue = 5 | pages = 423–441 | date = May 2017 | pmid = 28318897 | doi = 10.1016/j.euroneuro.2017.03.003 | s2cid = 3740987 }}</ref><ref name="pmid28590365">{{cite journal | vauthors = McIntyre RS, Lee Y, Zhou AJ, Rosenblat JD, Peters EM, Lam RW, Kennedy SH, Rong C, Jerrell JM | title = The Efficacy of Psychostimulants in Major Depressive Episodes: A Systematic Review and Meta-Analysis | journal = Journal of Clinical Psychopharmacology | volume = 37 | issue = 4 | pages = 412–418 | date = August 2017 | pmid = 28590365 | doi = 10.1097/JCP.0000000000000723 | s2cid = 27622964 }}</ref><ref name="pmid34144366">{{cite journal | vauthors = Bahji A, Mesbah-Oskui L | title = Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis | journal = Journal of Affective Disorders | volume = 292 | pages = 416–423 | date = September 2021 | pmid = 34144366 | doi = 10.1016/j.jad.2021.05.119 }}</ref> In a 2021 [[systematic review]] and meta-analysis of [[randomized controlled trial]]s of [[psychostimulant]]s for depression, modafinil and other stimulants such as [[methylphenidate]] and amphetamines improved depression in traditional meta-analysis.<ref name="pmid34144366" /> However, when subjected to [[network meta-analysis]], modafinil and most other stimulants did not significantly improve depression, with only methylphenidate remaining effective.<ref name="pmid34144366" /> Modafinil and other stimulants likewise did not improve [[quality of life]] in the meta-analysis, although there was evidence for reduced fatigue and sleepiness with modafinil and other stimulants.<ref name="pmid34144366" /> While significant effectiveness of modafinil for depression has been reported by particular trials,<ref name="pmid25295426">{{cite journal | vauthors = Corp SA, Gitlin MJ, Altshuler LL | title = A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder | journal = The Journal of Clinical Psychiatry | volume = 75 | issue = 9 | pages = 1010–1018 | date = September 2014 | pmid = 25295426 | doi = 10.4088/JCP.13r08851 }}</ref><ref name="pmid28590365" /><ref name="pmid24330897">{{cite journal | vauthors = Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH | title = Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials | journal = The Journal of Clinical Psychiatry | volume = 74 | issue = 11 | pages = 1101–1107 | date = November 2013 | pmid = 24330897 | doi = 10.4088/JCP.13r08560 }}</ref> reviews and meta-analyses note that the effectiveness of modafinil for depression is limited, the quality of available evidence is low, and the results are inconclusive.<ref name="pmid34144366" /><ref name="pmid26906078">{{cite journal | vauthors = Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, Mulder R, Porter R, Singh A, Murray G | title = Stimulants for depression: On the up and up? | journal = The Australian and New Zealand Journal of Psychiatry | volume = 50 | issue = 3 | pages = 203–207 | date = March 2016 | pmid = 26906078 | doi = 10.1177/0004867416634208 | s2cid = 45341424 }}</ref><ref name="pmid35174594">{{cite journal | vauthors = Miskowiak KW, Seeberg I, Jensen MB, Balanzá-Martínez V, Del Mar Bonnin C, Bowie CR, Carvalho AF, Dols A, Douglas K, Gallagher P, Hasler G, Lafer B, Lewandowski KE, López-Jaramillo C, Martinez-Aran A, McIntyre RS, Porter RJ, Purdon SE, Schaffer A, Stokes P, Sumiyoshi T, Torres IJ, Van Rheenen TE, Yatham LN, Young AH, Kessing LV, Burdick KE, Vieta E | title = Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force | journal = Bipolar Disorders | volume = 24 | issue = 4 | pages = 354–374 | date = June 2022 | pmid = 35174594 | pmc = 9541874 | doi = 10.1111/bdi.13193 }}</ref>

====Attention deficit hyperactivity disorder (research)==== <!-- This "(research)" in the heading is not redundant, it is used to distinguish between the same topic in the uses section, and is used as a wikilink target. -->
Modafinil was considered for the treatment of ADHD because of its lower [[abuse potential]] than conventional psychostimulants<ref name="pmid38725665"/> like methylphenidate and amphetamines.<ref name="pmid16623645" /><ref name="pmid27810669">{{cite journal | vauthors = Wang SM, Han C, Lee SJ, Jun TY, Patkar AA, Masand PS, Pae CU | title = Modafinil for the treatment of attention-deficit/hyperactivity disorder: A meta-analysis | journal = Journal of Psychiatric Research | volume = 84 | pages = 292–300 | date = January 2017 | pmid = 27810669 | doi = 10.1016/j.jpsychires.2016.09.034 }}</ref> In 2008, an application to market modafinil for pediatric ADHD was submitted to the [[Food and Drug Administration]] in the US.<ref name="pmid18729534">{{cite journal | vauthors = Kumar R | title = Approved and Investigational Uses of Modafinil | journal = Drugs | volume = 68 | issue = 13 | pages = 1803–1839 | year = 2008 | pmid = 18729534 | doi = 10.2165/00003495-200868130-00003 | s2cid = 38542387 }}</ref><ref name="pmid38433530"/>

However, evidence of modafinil for treatment of adult ADHD is mixed, and a 2016 systematic review of alternative drug therapies for adult ADHD did not recommend its use in this context.<ref name="pmid26693882">{{cite journal | vauthors = Buoli M, Serati M, Cahn W | title = Alternative pharmacological strategies for adult ADHD treatment: a systematic review | journal = Expert Review of Neurotherapeutics | volume = 16 | issue = 2 | pages = 131–144 | date = 2016 | pmid = 26693882 | doi = 10.1586/14737175.2016.1135735 | s2cid = 33004517 }}</ref> In a later large [[Phase III trial|phase&nbsp;3]] clinical trial of modafinil for adult ADHD, modafinil was not effective in improving symptoms, there was also a high rate of side effects (86%) and discontinuation (47%).<ref name="pmid30453134">{{cite journal | vauthors = Kooij JJ, Bijlenga D, Salerno L, Jaeschke R, Bitter I, Balázs J, Thome J, Dom G, Kasper S, Nunes Filipe C, Stes S, Mohr P, Leppämäki S, Casas M, Bobes J, Mccarthy JM, Richarte V, Kjems Philipsen A, Pehlivanidis A, Niemela A, Styr B, Semerci B, Bolea-Alamanac B, Edvinsson D, Baeyens D, Wynchank D, Sobanski E, Philipsen A, McNicholas F, Caci H, Mihailescu I, Manor I, Dobrescu I, Saito T, Krause J, Fayyad J, Ramos-Quiroga JA, Foeken K, Rad F, Adamou M, Ohlmeier M, Fitzgerald M, Gill M, Lensing M, Motavalli Mukaddes N, Brudkiewicz P, Gustafsson P, Tani P, Oswald P, Carpentier PJ, De Rossi P, Delorme R, Markovska Simoska S, Pallanti S, Young S, Bejerot S, Lehtonen T, Kustow J, Müller-Sedgwick U, Hirvikoski T, Pironti V, Ginsberg Y, Félegyházy Z, Garcia-Portilla MP, Asherson P | title = Updated European Consensus Statement on diagnosis and treatment of adult ADHD | journal = European Psychiatry | volume = 56 | pages = 14–34 | date = February 2019 | pmid = 30453134 | doi = 10.1016/j.eurpsy.2018.11.001 | s2cid = 53714228 | doi-access = free | title-link = doi | hdl = 10651/51910 | hdl-access = free }}</ref> The poor [[tolerability]] of modafinil in this study was possibly due to the use of high doses ({{Val|210|-|510|u=mg/day}}).<ref name="pmid30453134" /> Another reason for the denial of the approval was due to concerns about rare but serious dermatological toxicity in [[Stevens–Johnson syndrome]].<ref name="pmid18729534" />

The research on the use of modafinil for treating individuals with Autism Spectrum Disorder (ASD) who also exhibit ADHD symptoms is currently in its early stages with no results delivered.<ref name="pmid39004333">{{cite journal |vauthors=Martins PL, Torquato GC, Dias GA, Leite IB, Gaspar TM, Pinto JP, Macedo DS |title=Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis |journal=Prog Neuropsychopharmacol Biol Psychiatry |volume=134 |issue= |article-number=111089 |date=August 2024 |pmid=39004333 |doi=10.1016/j.pnpbp.2024.111089 |url=}}</ref>

====Substance dependence====
Modafinil was studied for the treatment of [[stimulant dependence]], but the results are mixed and inconclusive.<ref name="pmid32927246"/><ref name="pmid34121988">{{cite journal | vauthors = Hersey M, Bacon AK, Bailey LG, Coggiano MA, Newman AH, Leggio L, Tanda G | title = Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap? | journal = Frontiers in Neuroscience | volume = 15 | article-number = 656475 | date = 2021 | pmid = 34121988 | pmc = 8187604 | doi = 10.3389/fnins.2021.656475 | doi-access = free | title-link = doi }}</ref> Modafinil is not a [[controlled substance]] in some countries, unlike other medications, such as [[bupropion]], which is also used to treat [[Major depressive disorder|depression]] and [[nicotine dependence]].<ref name="pmid32601988">{{cite journal | vauthors = Tardelli VS, Bisaga A, Arcadepani FB, Gerra G, Levin FR, Fidalgo TM | title = Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis | journal = Psychopharmacology | location = Berlin | volume = 237 | issue = 8 | pages = 2233–2255 | date = August 2020 | pmid = 32601988 | doi = 10.1007/s00213-020-05563-3 | s2cid = 220150476 }}</ref> The clinical trials that have tested modafinil as a treatment for stimulant abuse have failed to demonstrate its efficacy and the optimal dose and duration of modafinil treatment remain unclear, and modafinil is not a recommended treatment for stimulant abuse.<ref name="pmid32601988"/> 2024 reviews found that modafinil was ineffective for treating individuals with [[amphetamine dependence|amphetamine-type stimulant use disorder]]<ref name="ElkriefSharafiBakouni2024"/> or [[methamphetamine use disorder]]<ref name="pmid39228432">{{cite journal |vauthors=Yates JR |title=Pharmacological Treatments for Methamphetamine Use Disorder: Current Status and Future Targets |journal=Subst Abuse Rehabil |volume=15 |issue= |pages=125–161 |date=2024 |pmid=39228432 |pmc=11370775 |doi=10.2147/SAR.S431273|doi-access=free }}</ref> from these dependencies.<ref name="pmid39228432"/><ref name="ElkriefSharafiBakouni2024">{{cite journal | vauthors = Elkrief L, Sharafi H, Bakouni H, McAnulty C, Bastien G, Dubreucq S, Garel N, Trépanier A, Ziegler D, Jutras-Aswad D | title = Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials | journal = The Canadian Journal of Psychiatry | date = July 2024 | volume = 69 | issue = 11 | pages = 793–805 | pmid = 39033427 | doi = 10.1177/07067437241262967 | pmc = 11572177 }}</ref>

====Schizophrenia====
Modafinil and armodafinil were studied as a complement to [[antipsychotic]] medications in the treatment of [[schizophrenia]]. They showed no effect on positive symptoms or cognitive performance.<ref name="pmid20816042">{{cite journal | vauthors = Kane JM, D'Souza DC, Patkar AA, Youakim JM, Tiller JM, Yang R, Keefe RS | title = Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 11 | pages = 1475–1481 | date = November 2010 | pmid = 20816042 | doi = 10.4088/jcp.09m05950gry }}</ref><ref name="pmid25306261" /> A 2015 [[meta-analysis]] found that modafinil and armodafinil may slightly reduce negative symptoms in people with acute schizophrenia, though they do not appear useful for people with the condition who are stable, with high negative symptom scores.<ref name="pmid25306261">{{cite journal | vauthors = Andrade C, Kisely S, Monteiro I, Rao S | title = Antipsychotic augmentation with modafinil or armodafinil for negative symptoms of schizophrenia: systematic review and meta-analysis of randomized controlled trials | journal = Journal of Psychiatric Research | volume = 60 | pages = 14–21 | date = January 2015 | pmid = 25306261 | doi = 10.1016/j.jpsychires.2014.09.013 | url = https://espace.library.uq.edu.au/view/UQ:345290/UQ345290_OA.pdf }}</ref> Among medications demonstrated to be effective for reducing negative symptoms in combination with antipsychotics, modafinil, and armodafinil are among the smallest [[effect size]]s.<ref name="pmid28514486">{{cite journal | vauthors = Correll CU, Rubio JM, Inczedy-Farkas G, Birnbaum ML, Kane JM, Leucht S | title = Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic Monotherapy in Schizophrenia: Systematic Overview and Quality Appraisal of the Meta-analytic Evidence | journal = JAMA Psychiatry | volume = 74 | issue = 7 | pages = 675–684 | date = July 2017 | pmid = 28514486 | pmc = 6584320 | doi = 10.1001/jamapsychiatry.2017.0624 }}</ref>

====Abstinence in cocaine addiction====
Modafinil is researched to determine whether it might improve abstinence in people with [[cocaine addiction]].<ref name="pmid28350194">{{cite journal | vauthors = Sangroula D, Motiwala F, Wagle B, Shah VC, Hagi K, Lippmann S | title = Modafinil Treatment of Cocaine Dependence: A Systematic Review and Meta-Analysis | journal = Substance Use & Misuse | volume = 52 | issue = 10 | pages = 1292–1306 | date = August 2017 | pmid = 28350194 | doi = 10.1080/10826084.2016.1276597 | s2cid = 4775658 }}</ref>

====Motivational disorders====
Modafinil has been found to reverse [[tetrabenazine]]-induced [[motivational disorder|motivational deficit]]s in animals and hence can produce [[pro-motivational agent|pro-motivational]] effects.<ref name="SalamoneCorrea2024">{{cite journal | vauthors = Salamone JD, Correa M | title = The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine | journal = Annu Rev Psychol | volume = 75 | issue = | pages = 1–32 | date = January 2024 | pmid = 37788571 | doi = 10.1146/annurev-psych-020223-012208 | url = | hdl = 10234/207207 | hdl-access = free }}</ref><ref name="SalamoneYohnLópez-Cruz2016">{{cite journal | vauthors = Salamone JD, Yohn SE, López-Cruz L, San Miguel N, Correa M | title = Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology | journal = Brain | volume = 139 | issue = Pt 5 | pages = 1325–1347 | date = May 2016 | pmid = 27189581 | pmc = 5839596 | doi = 10.1093/brain/aww050 | url = }}</ref><ref name="YohnGogojHaque2016">{{cite journal | vauthors = Yohn SE, Gogoj A, Haque A, Lopez-Cruz L, Haley A, Huxley P, Baskin P, Correa M, Salamone JD | title = Evaluation of the effort-related motivational effects of the novel dopamine uptake inhibitor PRX-14040 | journal = Pharmacol Biochem Behav | volume = 148 | issue = | pages = 84–91 | date = September 2016 | pmid = 27296079 | doi = 10.1016/j.pbb.2016.06.004 | url = }}</ref> Novel modafinil [[structural analog|analog]]s with greater [[potency (pharmacology)|potency]], including [[CE-123]], [[CE-158]], [[JJC8-088]], [[(S)-MK-26|MK-26]], and [[RDS03-94]], have also been developed and have shown pro-motivational effects in animals.<ref name="SalamoneCorrea2024" /><ref name="EcevitogluMekaRotolo2024">{{cite journal | vauthors = Ecevitoglu A, Meka N, Rotolo RA, Edelstein GA, Srinath S, Beard KR, Carratala-Ros C, Presby RE, Cao J, Okorom A, Newman AH, Correa M, Salamone JD | title = Potential therapeutics for effort-related motivational dysfunction: assessing novel atypical dopamine transport inhibitors | journal = Neuropsychopharmacology | volume = 49 | issue = 8 | pages = 1309–1317 | date = July 2024 | pmid = 38429498 | doi = 10.1038/s41386-024-01826-1 | pmc = 11224370 | url = }}</ref> These agents are of potential interest in the treatment of [[motivational disorder]]s in humans.<ref name="SalamoneCorrea2024" /><ref name="EcevitogluMekaRotolo2024" />

===Cognitive enhancement===
A 2019 review conducted on the potential nootropic effects of modafinil in healthy, non-sleep-deprived individuals revealed the following:<ref name="pmid31433334">{{cite journal | vauthors = Kredlow MA, Keshishian A, Oppenheimer S, Otto MW | title = The Efficacy of Modafinil as a Cognitive Enhancer: A Systematic Review and Meta-Analysis | journal = Journal of Clinical Psychopharmacology | volume = 39 | issue = 5 | pages = 455–461 | date = 2019 | pmid = 31433334 | doi = 10.1097/JCP.0000000000001085 | s2cid = 201119084 }}</ref> a) while studies using basic testing paradigms demonstrated that modafinil enhances [[executive function]], only half of these studies showed improvements in attention, learning, and memory, with a few studies even reporting impairments in divergent creative thinking; b) modafinil displayed small levels of enhancement in attention, executive functions, and learning abilities; c) no substantial side effects or mood changes were observed; d) the available evidence showed limited evidence for modafinil as a cognitive enhancer outside of its use for sleep-deprived populations.

A 2020 review reported that modafinil has a modest effect on memory updating, but the effect is small and may not accurately reflect the perception that it is useful as a cognitive enhancer, as there is insufficient evidence to support such a claim.<ref name="pmid32709551">{{cite journal | vauthors = Roberts CA, Jones A, Sumnall H, Gage SH, Montgomery C | title = How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and D-amphetamine | journal = European Neuropsychopharmacology | volume = 38 | pages = 40–62 | date = September 2020 | pmid = 32709551 | doi = 10.1016/j.euroneuro.2020.07.002 | url = https://researchonline.ljmu.ac.uk/id/eprint/13268/8/How%20effective%20are%20pharmaceuticals%20for%20cognitive%20enhancement%20in%20healthy%20adults%20A%20series%20of%20meta-analyses%20of%20cognitive%20performance%20during%20acute%20administration%20of%20modafinil%2C%20methylphenidate%20and%20d-amphetamine..pdf | url-status = live | s2cid = 220651670 | archive-url = https://web.archive.org/web/20220220101717/https://researchonline.ljmu.ac.uk/id/eprint/13268/8/How%20effective%20are%20pharmaceuticals%20for%20cognitive%20enhancement%20in%20healthy%20adults%20A%20series%20of%20meta-analyses%20of%20cognitive%20performance%20during%20acute%20administration%20of%20modafinil%2C%20methylphenidate%20and%20d-amphetamine..pdf | archive-date = February 20, 2022 }}</ref>

===Post-anesthesia sedation===
[[General anesthesia]] is required for many [[surgery|surgeries]], but may cause lingering fatigue, sedation, and/or drowsiness after surgery that lasts for hours to days.<ref name="Behar-2007">{{cite journal| doi=10.1136/sbmj.070256 | title=Anaesthesia: Induction and maintenance of general anesthesia | date=2007 | journal=BMJ | volume=334 | vauthors = Behar JM, Gogalniceanu P, Bromley L }}</ref><ref name="pmid34338712">{{cite journal |vauthors=Vacas S, Cole DJ, Cannesson M |title=Cognitive Decline Associated With Anesthesia and Surgery in Older Patients |journal=JAMA |date=August 2021 |volume=326 |issue=9 |page=863 |pmid=34338712 |pmc=8807795 |doi=10.1001/jama.2021.4773}}</ref> In [[outpatient surgery]] the [[sedation]], [[fatigue]], and occasional [[dizziness]] is problematic.<ref name="pmid12411816">{{cite journal|doi=10.1097/00000542-200211000-00035 |title=Fatigue in Anesthesia |date=2002 |journal=Anesthesiology |volume=97 |issue=5 |pages=1281–1294 |pmid=12411816 | vauthors = Warltier DC, Howard SK, Rosekind MR, Katz JD, Berry AJ }}</ref><ref name="pmid11964610">{{cite journal|doi=10.1097/00000542-200204000-00030 |title=Systematic Review and Analysis of Postdischarge Symptoms after Outpatient Surgery |date=2002 |journal=Anesthesiology |volume=96 |issue=4 |pages=994–1003 |pmid=11964610 | vauthors = Wu CL, Berenholtz SM, Pronovost PJ, Fleisher LA }}</ref> Modafinil was tested as a potential remedy to alleviate these symptoms.<ref name="pmid16669720"/> For example, it was expected that modafinil would help people recover quicker from general anesthesia after a short surgery,<ref name="pmid18729534"/> but the results were uncertain and the inconclusive studies could not reliably verify the expectation.<ref name="pmid16669720">{{cite journal | vauthors = Ballon JS, Feifel D | title = A systematic review of modafinil: Potential clinical uses and mechanisms of action | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = 4 | pages = 554–566 | date = April 2006 | pmid = 16669720 | doi = 10.4088/jcp.v67n0406 }}</ref> The use of modafinil to relieve post-anesthesia sedation is investigational.<ref name="pmid18729534"/>

===Postural orthostatic tachycardia syndrome===
Caution should be exercised in people who have narcolepsy in [[comorbidity]] with [[postural orthostatic tachycardia syndrome]] (POTS).<ref name="pmid16943900">{{cite journal |vauthors=Raj SR |title=The Postural Tachycardia Syndrome (POTS): pathophysiology, diagnosis & management |journal=Indian Pacing Electrophysiol J |volume=6 |issue=2 |pages=84–99 |date=April 2006 |pmid=16943900 |pmc=1501099}}</ref>

===Myotonic dystrophy===
Modafinil is being researched as a potential remedy for excessive daytime sleepiness in [[myotonic dystrophy]] (DM), an inherited condition characterized by progressive muscle loss, weakness, and [[myotonia.]] Myotonia is a condition where muscles cannot relax after they contract.<ref name="pmid39011358">{{cite journal |vauthors=Hoxhaj D, Pascazio A, Maestri M, Ricci G, Fabbrini M, Torresi FB, Siciliano G, Bonanni E |title=Excessive daytime sleepiness in myotonic dystrophy: a narrative review |journal=Front Neurol |volume=15 |issue= |article-number=1389949 |date=2024 |pmid=39011358 |pmc=11248093 |doi=10.3389/fneur.2024.1389949|doi-access=free }}</ref> Myotonic dystrophy has two main types: DM1 (Steinert disease) and DM2 (proximal myotonic myopathy). Both types can cause excessive daytime sleepiness. Studies suggest that modafinil may be a promising drug that can reduce both daytime sleepiness and myotonia itself, without significant cardiac conduction effects. These presumed property of modafinil is of particular interest for eventual treatment of people with myotonic dystrophy who often have underlying cardiac issues.<ref name="pmid39011358"/> Still, modafinil is not approved by the FDA for use in myotonic dystrophy, and the value and role of modafinil in DM remain the subject of debate.<ref name="pmid39011358"/>

===Disorders of consciousness===
Modafinil has been studied for its potential therapeutic effects in patients with [[Disorder of consciousness|disorders of consciousness]].<ref name="pmid39019729"/> Researchers are investigating whether modafinil can stimulate [[neurotransmitter]]s such as [[histamine]], [[norepinephrine]], [[serotonin]], [[dopamine]], and [[orexin]], and whether modafinil has potential [[Anti-oxidative|anti-oxidative effects]].<ref name="pmid39019729">{{cite journal |vauthors=Barra ME, Solt K, Yu X, Edlow BL |title=Restoring consciousness with pharmacologic therapy: Mechanisms, targets, and future directions |journal=Neurotherapeutics |volume=21 |issue=4 |article-number=e00374 |date=July 2024 |pmid=39019729 |pmc=11452330 |doi=10.1016/j.neurot.2024.e00374}}</ref>

Disorders of consciousness are states characterized by impaired arousal and awareness.<ref name="pmid39019729"/> These states include [[coma]], [[vegetative state]]/[[unresponsive wakefulness syndrome]] (VS/UWS), [[minimally conscious state]] (MCS), [[cognitive motor dissociation]], and [[covert cortical processing]].<ref name="pmid39019729"/> Brain injuries can impair consciousness through [[neuroanatomic lesions]] involving the [[bilateral cerebral hemispheres]], [[rostral brainstem]], [[diencephalon]], or [[basal forebrain]].<ref name="pmid39019729"/>

[[Neuroimaging]] studies have shown that modafinil increases [[cerebral blood flow]] in several brain regions, such as the [[thalamus]], [[locus coeruleus]], [[limbic system]], and [[insular cortex]];<ref name="pmid39019729"/> still, observational reports on the use of modafinil in patients with disorders of consciousness have produced mixed results, indicating that its effectiveness may vary among individuals.<ref name="pmid39019729"/>

===Inflammation===
A possible link between [[inflammation|inflammatory processes]] and depressive disorders<ref name="pmid27640518">{{cite journal | vauthors = Kohler O, Krogh J, Mors O, Benros ME | title = Inflammation in Depression and the Potential for Anti-Inflammatory Treatment | journal = Current Neuropharmacology | volume = 14 | issue = 7 | pages = 732–742 | date = 2016 | pmid = 27640518 | pmc = 5050394 | doi = 10.2174/1570159x14666151208113700 }}</ref> has stimulated preliminary research on modafinil for its potential anti-inflammatory effects.<ref name="pmid32311496">{{cite journal | vauthors = Zager A | title = Modulating the immune response with the wake-promoting drug modafinil: A potential therapeutic approach for inflammatory disorders | journal = Brain, Behavior, and Immunity | volume = 88 | pages = 878–886 | date = August 2020 | pmid = 32311496 | doi = 10.1016/j.bbi.2020.04.038 | s2cid = 215807973 }}</ref>

== References ==
{{Reflist}}

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