View source for Paroxetine

{{Short description|SSRI antidepressant medication}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 417832252
| image = Paroxetine-2D-skeletal.svg
| image_class = skin-invert-image
| width = 250
| alt = 
| image2 = Paroxetine-from-HCl-xtal-3D-balls.png
| width2 = 250
| alt2 = <!-- Clinical data -->
| pronounce = {{IPAc-en|p|ər|ˈ|ɑː|k|s|ə|ˌ|t|i|n|}}<br/ >{{respell|pər-AHK-sə-TEEN}}
| tradename = Paxil, others
| Drugs.com = {{drugs.com|monograph|paroxetine-hydrochloride}}
| MedlinePlus = a698032
| DailyMedID = Paroxetine
| pregnancy_AU = D
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[By mouth]]
| class = [[Selective serotonin reuptake inhibitor]] (SSRI)
| ATC_prefix = N06
| ATC_suffix = AB05
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = 
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 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=3 August 2023 |access-date=3 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = 
| 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 = 
| legal_US = Rx-only
| legal_US_comment = 
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = Rx-only

<!-- Pharmacokinetic data -->| bioavailability = Extensively absorbed from the GI tract, but extensive [[first pass effect|first-pass metabolism]] in the liver<ref name = TGA>{{cite web|title=Product Information Paroxetine Sandoz 20Mg Film-Coated Tablets |author=Sandoz Pty Ltd|author-link=Sandoz|website=Therapeutic Goods Administration|date=18 January 2012|access-date=22 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03771-3|format=PDF|archive-url=https://web.archive.org/web/20150904113626/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03771-3|archive-date=4 September 2015|url-status=live}}</ref><ref name = DM>{{cite web|title=Paroxetine (paroxetine hydrochloride hemihydrate) tablet, film coated|website=DailyMed|author=Mylan Institutional Inc.|author-link=Mylan|publisher=U.S. National Library of Medicine|date=January 2012|access-date=22 November 2013|url=https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f235ee45-9517-45de-8df7-9a06fdb43380|archive-url=https://web.archive.org/web/20131023060245/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f235ee45-9517-45de-8df7-9a06fdb43380|archive-date=23 October 2013|url-status=live}}</ref><ref name = EMC>{{cite web|title=Paroxetine 20 mg Tablets – Summary of Product Characteristics (SPC)|website=electronic Medicines Compendium|author=Sandoz Limited|author-link=Sandoz|publisher=Datapharm Ltd|date=21 March 2013|access-date=22 November 2013|url=http://www.medicines.org.uk/emc/medicine/26634/SPC/Paroxetine+20+mg+Tablets/|archive-url=https://web.archive.org/web/20131203004705/http://www.medicines.org.uk/emc/medicine/26634/SPC/Paroxetine+20+mg+Tablets/|archive-date=3 December 2013|url-status=live}}</ref><ref name = MSR>{{cite web|title=Paxil, Paxil CR (paroxetine) dosing, indications, interactions, adverse effects, and more|website=Medscape Reference|publisher=WebMD|access-date=22 November 2013|url=http://reference.medscape.com/drug/paxil-brisdelle-paroxetine-342959|archive-url=https://web.archive.org/web/20151110133215/http://reference.medscape.com/drug/paxil-brisdelle-paroxetine-342959|archive-date=10 November 2015|url-status=live}}</ref>
| protein_bound = 93–95%<ref name = TGA/><ref name = DM/><ref name = EMC/>
| metabolism = Extensive, [[liver]] (mostly [[CYP2D6]]-mediated)<ref name = TGA/><ref name = DM/><ref name = EMC/>
| metabolites = 
| onset = 
| elimination_half-life = 21 hours<ref name = TGA/><ref name = DM/><ref name = EMC/>
| duration_of_action = 
| excretion = [[Kidney]] (64%; 2% unchanged and 62% as metabolites), [[faeces|faecal]] (36%; <1% unchanged)<ref name = TGA/><ref name =DM/><ref name = EMC/>

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 61869-08-7
| PubChem = 43815
| IUPHAR_ligand = 4790
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00715
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 39888
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 41VRH5220H
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02362
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 7936
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 490
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = <!-- Chemical and physical data -->
| IUPAC_name = (3''S'',4''R'')-3-[(2''H''-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine
| C = 19
| H = 20
| F = 1
| N = 1
| O = 3
| smiles = c1cc(ccc1[C@@H]2CCNC[C@H]2COc3ccc4c(c3)OCO4)F
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H20FNO3/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18/h1-6,9,14,17,21H,7-8,10-12H2/t14-,17-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AHOUBRCZNHFOSL-YOEHRIQHSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Paroxetine''', sold under the brand name '''Paxil''' among others, is an [[Antidepressant| antidepressant medication]] of the [[selective serotonin reuptake inhibitor]] (SSRI) class<ref name=AHFS2019>{{cite web|url=https://www.drugs.com/monograph/paroxetine-hydrochloride.html|title=Paroxetine Hydrochloride Monograph for Professionals|website=Drugs.com|publisher=American Society of Health-System Pharmacists|access-date=3 March 2019|archive-url=https://web.archive.org/web/20190306043802/https://www.drugs.com/monograph/paroxetine-hydrochloride.html|archive-date=6 March 2019|url-status=live}}</ref> used to treat [[major depressive disorder]], [[obsessive-compulsive disorder|obsessive–compulsive disorder]] (OCD), [[panic disorder]], [[social anxiety disorder]], [[post-traumatic stress disorder]] (PTSD), [[generalized anxiety disorder]], and [[premenstrual dysphoric disorder]].<ref name=AHFS2019/> It has also been used in the treatment of [[premature ejaculation]], and [[hot flash]]es due to [[menopause]].<ref name=AHFS2019/><ref name=FDA2013>{{cite press release|title=FDA approves the first non-hormonal treatment for hot flashes associated with menopause| vauthors = Fischer A |publisher=Food and Drug Administration|date=28 June 2013|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm359030.htm|archive-url=https://web.archive.org/web/20170118091242/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm359030.htm |archive-date=18 January 2017}}</ref> It is taken [[oral administration|orally]] (by mouth).<ref name=AHFS2019/>

<!-- Side effects -->
Common side effects include drowsiness, dry mouth, loss of appetite, sweating, [[insomnia|trouble sleeping]], and [[sexual dysfunction]].<ref name=AHFS2019/> Serious side effects may include suicidal thoughts in those under the age of 25, [[serotonin syndrome]], and [[mania]].<ref name=AHFS2019/> While the rate of side effects appears similar compared to other SSRIs and [[SNRIs]], [[antidepressant discontinuation syndrome]] may occur more often.<ref name="ReferenceD">{{cite journal | vauthors = Hosenbocus S, Chahal R | title = SSRIs and SNRIs: A review of the Discontinuation Syndrome in Children and Adolescents | journal = Journal of the Canadian Academy of Child and Adolescent Psychiatry | volume = 20 | issue = 1 | pages = 60–67 | date = February 2011 | pmid = 21286371 | pmc = 3024727 }}</ref><ref name="ReferenceE">{{cite journal | vauthors = Pae CU, Patkar AA | title = Paroxetine: current status in psychiatry | journal = Expert Review of Neurotherapeutics | volume = 7 | issue = 2 | pages = 107–120 | date = February 2007 | pmid = 17286545 | doi = 10.1586/14737175.7.2.107 | s2cid = 34636522 }}</ref> Use in [[pregnancy]] is not recommended, while use during [[breastfeeding]] is relatively safe.<ref name=Preg2019>{{cite web|title=Paroxetine Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/paroxetine.html |publisher=Drugs.com |access-date=3 March 2019 |archive-url=https://web.archive.org/web/20181203131613/https://www.drugs.com/pregnancy/paroxetine.html |archive-date=3 December 2018 |url-status=live}}</ref> It is believed to work by blocking the reuptake of the chemical [[serotonin]] by [[neurons]] in the brain.<ref name=AHFS2019/>

<!-- History, society and culture -->
Paroxetine was approved for medical use in the United States in 1992 and initially sold by [[GlaxoSmithKline]].<ref name=AHFS2019/><ref>{{cite book |author=Food and Drug Administration |title=Approved Drug Products with Therapeutic Equivalence Evaluations – FDA Orange Book 31st Edition (2011): FDA Orange Book 31st Edition (2011) |date=2011 |publisher=DrugPatentWatch.com |isbn=978-1-934899-81-6 |page=344 |url=https://books.google.com/books?id=JDZ4DAAAQBAJ&pg=PR344 |access-date=4 March 2019 |archive-url=https://web.archive.org/web/20190306043352/https://books.google.ca/books?id=JDZ4DAAAQBAJ&pg=PR344 |archive-date=6 March 2019 |url-status=live}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=BNF76>{{cite book|title=British national formulary: BNF 76 |date=2018 |publisher=Pharmaceutical Press |isbn=978-0-85711-338-2|pages=363|edition=76}}</ref> In 2023, it was the 72nd most commonly prescribed medication in the United States, with more than 9{{nbsp}}million prescriptions.<ref name="Top300Drugs">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref name="ClinCalc Paroxetine">{{cite web | title = Paroxetine Drug Usage Statistics, United States, 2013 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Paroxetine | access-date = 18 August 2025 }}</ref> In 2018, it was in the top 10 of most prescribed [[antidepressant]]s in the United States.<ref>{{Cite web |vauthors=Grohol JM |date=15 December 2019 |title=Top 25 Psychiatric Medications for 2018 |url=https://psychcentral.com/blog/top-25-psychiatric-medications-for-2018/ |access-date=26 September 2020 |website=psychcentral.com |archive-date=25 October 2020 |archive-url=https://web.archive.org/web/20201025001611/https://psychcentral.com/blog/top-25-psychiatric-medications-for-2018/ |url-status=live }}</ref>

==Medical uses==
Paroxetine is primarily used to treat [[major depressive disorder]], [[obsessive-compulsive disorder|obsessive–compulsive disorder]], [[post-traumatic stress disorder]], [[social anxiety disorder]], and [[panic disorder]]. It is also occasionally used for [[agoraphobia]], [[generalized anxiety disorder]], [[premenstrual dysphoric disorder]], and menopausal [[hot flash]]es.<ref>{{cite journal | vauthors = Wagstaff AJ, Cheer SM, Matheson AJ, Ormrod D, Goa KL | title = Paroxetine: an update of its use in psychiatric disorders in adults | journal = Drugs | volume = 62 | issue = 4 | pages = 655–703 | date = March 2002 | pmid = 11893234 | doi = 10.2165/00003495-200262040-00010 | s2cid = 195692589 }}</ref><ref>{{Cite journal|vauthors=Lotke P, Garcia F, Stearns V, Beebe KL, Iyengar M |title=Paroxetine controlled release was effective and tolerable for treating menopausal hot flash symptoms in women |url=http://ebm.bmj.com/content/9/1/23.full|journal=Evidence Based Medicine |date=1 January 2004 |issn=1473-6810 |page=23 |volume=9 |issue=1 |doi=10.1136/ebm.9.1.23 |doi-access=free |access-date=20 January 2017 |archive-url=https://web.archive.org/web/20160214212936/http://ebm.bmj.com/content/9/1/23.full |archive-date=14 February 2016 |url-status=live}}</ref><ref>{{Cite web|url=https://www.nhs.uk/medicines/paroxetine/|title=Paroxetine: an antidepressant |date=29 August 2018 |website=nhs.uk |access-date=15 March 2020 |archive-url=https://web.archive.org/web/20200514090938/https://www.nhs.uk/medicines/paroxetine/ |archive-date=14 May 2020 |url-status=live}}</ref><ref>{{Cite web |url=https://www.medicines.org.uk/emc/product/4168/smpc |title=Paroxetine 20 mg Tablets - Summary of Product Characteristics (SmPC) - (emc) |website=medicines.org.uk |access-date=15 March 2020 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828205844/https://www.medicines.org.uk/emc/product/4168/smpc |url-status=live }}</ref><ref>{{Cite web|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=paroxetine|title=Product and Consumer Medicine Information|publisher=Therapeutic Goods Administration|access-date=15 March 2020|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828205845/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm=&t=&q=paroxetine|url-status=live}}</ref>

===Depression===
A variety of meta-analyses have been conducted to evaluate the efficacy of paroxetine in depression. They have variously concluded that paroxetine is superior to placebo and that it is equivalent to other antidepressants.<ref>{{cite journal | vauthors = Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C | title = Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis | journal = Lancet | volume = 373 | issue = 9665 | pages = 746–758 | date = February 2009 | pmid = 19185342 | doi = 10.1016/S0140-6736(09)60046-5 | s2cid = 35858125 }}</ref><ref>{{cite journal | vauthors = Fava M, Amsterdam JD, Deltito JA, Salzman C, Schwaller M, Dunner DL | title = A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression | journal = Annals of Clinical Psychiatry | volume = 10 | issue = 4 | pages = 145–150 | date = December 1998 | pmid = 9988054 | doi = 10.3109/10401239809147030 }}</ref><ref name="ReferenceF">{{cite journal | vauthors = Sugarman MA, Loree AM, Baltes BB, Grekin ER, Kirsch I | title = The efficacy of paroxetine and placebo in treating anxiety and depression: a meta-analysis of change on the Hamilton Rating Scales | journal = PLOS ONE | volume = 9 | issue = 8 | article-number = e106337 | date = 27 August 2014 | pmid = 25162656 | pmc = 4146610 | doi = 10.1371/journal.pone.0106337 | doi-access = free | bibcode = 2014PLoSO...9j6337S }}</ref> Despite this, there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any point in time.<ref>{{cite journal | vauthors = Purgato M, Papola D, Gastaldon C, Trespidi C, Magni LR, Rizzo C, Furukawa TA, Watanabe N, Cipriani A, Barbui C | title = Paroxetine versus other anti-depressive agents for depression | journal = The Cochrane Database of Systematic Reviews | issue = 4 | article-number = CD006531 | date = April 2014 | volume = 2014 | pmid = 24696195 | doi = 10.1002/14651858.cd006531.pub2 | pmc = 10091826 | doi-access = free }}</ref>

=== Anxiety disorders ===
<!-- Panic disorder -->
Paroxetine was the first antidepressant approved in the United States for the treatment of panic disorder.<ref>{{cite book|title=Social Work Diagnosis in Contemporary Practice | vauthors = Turner FJ |year=2005 |publisher=Oxford University Press US |isbn=978-0-19-516878-5}}</ref>{{page needed|date=January 2017}} Several studies have concluded that paroxetine is superior to placebo in the treatment of panic disorder.<ref name="ReferenceF"/><ref>{{cite journal | vauthors = Ballenger JC, Wheadon DE, Steiner M, Bushnell W, Gergel IP | title = Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder | journal = The American Journal of Psychiatry | volume = 155 | issue = 1 | pages = 36–42 | date = January 1998 | pmid = 9433336 | doi = 10.1176/ajp.155.1.36 | doi-access = free }}</ref>

<!-- Social anxiety disorder -->
Paroxetine has demonstrated efficacy for the treatment of social anxiety disorder in adults and children.<ref>{{cite journal | vauthors = Stein MB, Liebowitz MR, Lydiard RB, Pitts CD, Bushnell W, Gergel I | title = Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial | journal = JAMA | volume = 280 | issue = 8 | pages = 708–713 | date = August 1998 | pmid = 9728642 | doi = 10.1001/jama.280.8.708 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Manassis K | title = Paroxetine improves social anxiety disorder in children and adolescents | journal = Evidence-Based Mental Health | volume = 8 | issue = 2 | page = 43 | date = May 2005 | pmid = 15851806 | doi = 10.1136/ebmh.8.2.43 | url = http://ebmh.bmj.com/content/8/2/43.full | access-date = 20 January 2017 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20170827171952/http://ebmh.bmj.com/content/8/2/43.full | archive-date = 27 August 2017 }}</ref> It is also beneficial for people with co-occurring social anxiety disorder and [[alcohol use disorder]].<ref>{{cite journal | vauthors = Randall CL, Johnson MR, Thevos AK, Sonne SC, Thomas SE, Willard SL, Brady KT, Davidson JR | title = Paroxetine for social anxiety and alcohol use in dual-diagnosed patients | journal = Depression and Anxiety | volume = 14 | issue = 4 | pages = 255–262 | date = 1 January 2001 | pmid = 11754136 | doi = 10.1002/da.1077 | s2cid = 23395959 | doi-access = free }}</ref> It appears to be similar to a number of other SSRIs.<ref>{{cite journal | vauthors = Blanco C, Bragdon LB, Schneier FR, Liebowitz MR | title = The evidence-based pharmacotherapy of social anxiety disorder | journal = The International Journal of Neuropsychopharmacology | volume = 16 | issue = 1 | pages = 235–249 | date = February 2013 | pmid = 22436306 | doi = 10.1017/S1461145712000119 | quote = There were no significant differences between the three SSRIs that had been tested in placebo-controlled studies: paroxetine; sertraline; fluvoxamine. | doi-access = free }}</ref>

<!-- Obsessive-compulsive disorder -->
Paroxetine is used in the treatment of obsessive-compulsive disorder.<ref>{{cite journal | vauthors = Germann D, Ma G, Han F, Tikhomirova A | title = Paroxetine hydrochloride | journal = Profiles of Drug Substances, Excipients, and Related Methodology | volume = 38 | pages = 367–406 | date = 2013 | pmid = 23668408 | doi = 10.1016/B978-0-12-407691-4.00008-3 | isbn = 978-0-12-407691-4 | series = Analytical Profiles of Drug Substances and Excipients | s2cid = 205143838 | veditors = Brittain HG }}</ref> Comparative efficacy of paroxetine is equivalent to that of [[clomipramine]] and [[venlafaxine]].<ref>{{cite journal | vauthors = Zohar J, Judge R | title = Paroxetine versus clomipramine in the treatment of obsessive-compulsive disorder. OCD Paroxetine Study Investigators | journal = The British Journal of Psychiatry | volume = 169 | issue = 4 | pages = 468–474 | date = October 1996 | pmid = 8894198 | doi = 10.1192/bjp.169.4.468 | s2cid = 19698156 }}</ref><ref>{{cite journal | vauthors = Denys D, van der Wee N, van Megen HJ, Westenberg HG | title = A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder | journal = Journal of Clinical Psychopharmacology | volume = 23 | issue = 6 | pages = 568–575 | date = December 2003 | pmid = 14624187 | doi = 10.1097/01.jcp.0000095342.32154.54 | s2cid = 23260081 }}</ref> Paroxetine is also effective for children with obsessive-compulsive disorder.<ref>{{cite journal | vauthors = Ipser JC, Stein DJ, Hawkridge S, Hoppe L | title = Pharmacotherapy for anxiety disorders in children and adolescents | journal = The Cochrane Database of Systematic Reviews | issue = 3 | article-number = CD005170 | date = July 2009 | pmid = 19588367 | doi = 10.1002/14651858.CD005170.pub2 }}</ref>

<!-- Posttraumatic stress disorder -->
Paroxetine is approved for the treatment of PTSD in the United States, Japan, and Europe.<ref>{{cite journal | vauthors = Alexander W | title = Pharmacotherapy for Post-traumatic Stress Disorder In Combat Veterans: Focus on Antidepressants and Atypical Antipsychotic Agents | journal = P & T | volume = 37 | issue = 1 | pages = 32–38 | date = January 2012 | pmid = 22346334 | pmc = 3278188 }}</ref><ref name=Ip2011>{{cite journal | vauthors = Ipser JC, Stein DJ | title = Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD) | journal = The International Journal of Neuropsychopharmacology | volume = 15 | issue = 6 | pages = 825–840 | date = July 2012 | pmid = 21798109 | doi = 10.1017/S1461145711001209 | doi-access = free }}</ref><ref>{{Cite web|url=http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=34488|title=Search results detail{{!}} Kusurino-Shiori (Drug information Sheet)|website=rad-ar.or.jp|access-date=15 March 2019|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828205845/https://www.rad-ar.or.jp/siori/english/kekka.cgi?n=34488|url-status=live}}</ref> In the United States, it is approved for short-term use.<ref name=Ip2011/>

Paroxetine is also FDA-approved for generalized anxiety disorder.<ref>{{Cite journal|date=18 May 2001|title=FDA Approves Antidepressant For Generalized Anxiety Disorder|journal=Psychiatric News|volume=36|issue=10|page=14|doi=10.1176/pn.36.10.0014b}}</ref>

=== Menopausal hot flashes ===
In 2013, low-dose paroxetine was approved in the US for the treatment of moderate-to-severe [[vasomotor symptoms]] such as hot flashes and [[night sweats]] associated with menopause.<ref name=FDA2013/> At the low dose used for menopausal hot flashes, side effects are similar to placebo and dose tapering is not required for discontinuation.<ref name="OrleansLi2014">{{cite journal | vauthors = Orleans RJ, Li L, Kim MJ, Guo J, Sobhan M, Soule L, Joffe HV | title = FDA approval of paroxetine for menopausal hot flushes | journal = The New England Journal of Medicine | volume = 370 | issue = 19 | pages = 1777–1779 | date = May 2014 | pmid = 24806158 | doi = 10.1056/NEJMp1402080 | doi-access = free }}</ref>

=== Fibromyalgia ===
Studies have also shown paroxetine "appears to be well-tolerated and improve the overall symptomatology in patients with fibromyalgia", but is less robust in helping with the pain involved.<ref>{{cite journal | vauthors = Patkar AA, Masand PS, Krulewicz S, Mannelli P, Peindl K, Beebe KL, Jiang W | title = A randomized, controlled, trial of controlled release paroxetine in fibromyalgia | journal = The American Journal of Medicine | volume = 120 | issue = 5 | pages = 448–454 | date = May 2007 | pmid = 17466657 | doi = 10.1016/j.amjmed.2006.06.006 | doi-access = free }}</ref><ref>{{cite journal| vauthors = Giordano N, Geraci S, Santacroce C, Mattii G, Battisti E, Gennari C |date=December 1999|title=Efficacy and tolerability of paroxetine in patients with fibromyalgia syndrome: a single-blind study |journal=Current Therapeutic Research|volume=60|issue=12|pages=696–702|doi=10.1016/S0011-393X(99)90008-5 }}</ref>

==Adverse effects==
{{See also|List of adverse effects of paroxetine}}

Common side effects include drowsiness, dry mouth, loss of appetite, sweating, insomnia, and [[sexual dysfunction]].<ref name="AHFS2019" /> Serious side effects may include suicide in those under the age of 25, [[serotonin syndrome]], and [[mania]].<ref name="AHFS2019" /> While the rate of side effects appears similar compared to other SSRIs and SNRIs, antidepressant discontinuation syndromes may occur more often.<ref name="ReferenceD"/><ref name="ReferenceE"/> Use in pregnancy is not recommended, while use during [[breastfeeding]] is relatively safe.<ref name="Preg2019"/>

The Federal Aviation Administration (FAA), the U.S. agency responsible for regulating civil aviation, considers paroxetine to be an antidepressant medication that is ineligible for an FAA Authorization of Special Issuance (SI) or Special Consideration (SC) of a [[Medical certifications for pilots#United States|medical certificate]].<ref>{{Cite web |date=2024-04-24 |title=Guide for Aviation Medical Examiners |url=https://www.faa.gov/ame_guide/app_process/exam_tech/item47/amd/antidepressants |url-status=live |archive-url=https://web.archive.org/web/20250527122452/https://www.faa.gov/ame_guide/app_process/exam_tech/item47/amd/antidepressants |archive-date=27 May 2025 |access-date=2025-06-08 |website=Federal Aviation Administration |quote=An individual may be considered for an FAA Authorization of a Special Issuance (SI) or Special Consideration (SC) of a Medical Certificate (Authorization) if: […] 3. The medication used is one of the conditionally acceptable Antidepressant Medications […]. }}</ref>

Paroxetine shares many of the common adverse effects of SSRIs, including (with the corresponding rates seen in people treated with placebo in parentheses):
* nausea 26% (9%)
* [[somnolence]] 23% (9%)
* dry mouth 18% (12%)
* headache 18% (17%)
* asthenia (weakness) 15% (6%)
* constipation 14% (9%)
* dizziness 13% (6%)
* insomnia 13% (6%)
* diarrhea 12% (8%)
* sweating 11% (2%)
* tremor 8% (2%)
* loss of appetite 6% (2%)
* nervousness 5% (3%)
* blurred vision 4% (1%)
* [[paraesthesia]] 4% (2%)
* [[hypomania]] 1% (0.3%)
* sexual dysfunction (≥10% incidence).<ref name = MSR/>

Most of these adverse effects are transient and go away with continued treatment. Central and peripheral [[5-HT3 receptor|5-HT<sub>3</sub> receptor]] stimulation is believed to result in the gastrointestinal effects observed with SSRI treatment.<ref name = GG/> Compared to other SSRIs, it has a lower incidence of diarrhea, but a higher incidence of anticholinergic effects (e.g., dry mouth, constipation, blurred vision, etc.), sedation/somnolence/drowsiness, sexual side effects, and weight gain.<ref name="PhDep"/>

Due to reports of adverse withdrawal reactions upon terminating treatment, the [[Committee for Medicinal Products for Human Use]] <!-- (CHMP) --> at the [[European Medicines Agency]] recommends gradually reducing over several weeks or months if the decision to withdraw is made.<ref>{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500015202.pdf|publisher=European Medicines Agency|title=Press release, CHMP meeting on Paroxetine and other SSRIs|date=9 December 2004|access-date=24 August 2007|archive-url=https://web.archive.org/web/20150904113627/http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500015202.pdf|archive-date=4 September 2015|url-status=live}}</ref> See also [[#Discontinuation syndrome|Discontinuation syndrome (withdrawal)]].

Mania or [[hypomania]] may occur in 1% of patients with depression and up to 12% of patients with [[bipolar disorder]].<ref>{{cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020031s067,020710s031.pdf |title=Prescribing Information Paxil (paroxetine hydrochloride) Tablets and Oral Suspension |archive-url=https://web.archive.org/web/20140503202932/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020031s067,020710s031.pdf |archive-date=3 May 2014 }}</ref> This side effect can occur in individuals with no history of mania, but it may be more likely to occur in those with bipolar disorder or with a family history of mania.<ref>{{cite journal | vauthors = Morishita S, Arita S | title = Induction of mania in depression by paroxetine | journal = Human Psychopharmacology | volume = 18 | issue = 7 | pages = 565–568 | date = October 2003 | pmid = 14533140 | doi = 10.1002/hup.531 | s2cid = 32168369 }}</ref>

Paroxetine is described as a 'hepatoxic agent'<ref>{{cite web |title=Paroxetine |url=https://pubchem.ncbi.nlm.nih.gov/compound/Paroxetine |website=PubChem}}</ref> and has been associated with hepatoxicity and jaundice.<ref>{{cite journal |title=Severe hepatotoxicity with jaundice associated with paroxetine |url=https://www.sciencedirect.com/science/article/abs/pii/S0002927001026235 |journal=The American Journal of Gastroenterology|date=August 2001 |volume=96 |issue=8 |pages=2494–2496 |doi=10.1016/S0002-9270(01)02623-5 | vauthors = Odeh M, Misselevech I, Boss JH, Oliven A |pmid=11513198 |url-access=subscription }}</ref>

===Suicide===
Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in people under the age of 25.<ref>{{cite web|url=https://www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/UCM161646.pdf |title=Medication Guide About Using Antidepressants in Children and Teenagers |archive-url=https://web.archive.org/web/20160311075028/http://www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/UCM161646.pdf |archive-date=11 March 2016 |publisher=FDA}}</ref><ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108363.htm |title=FDA Launches a Multi-Pronged Strategy to Strengthen Safeguards for Children Treated With Antidepressant Medications |website=[[Food and Drug Administration]] |archive-url=https://web.archive.org/web/20170118093030/http://www.fda.gov/newsevents/newsroom/pressannouncements/2004/ucm108363.htm |archive-date=January 18, 2017 |date=October 15, 2004 }}</ref> The [[Food and Drug Administration|FDA]] conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004 and found an increase in suicidality and ideation as compared to placebo, which was observed in trials for both depression and anxiety disorders.<ref name=FDA1>{{cite web|url=https://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf |title=Review and evaluation of clinical data: relationship between psychotropic drugs and pediatric suicidality |access-date=27 January 2009 |vauthors=Hammad TA |date=16 August 2004 |website=Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Pediatric Advisory Committee. 13–14 September 2004. Briefing Information. |publisher=FDA |page=30 |archive-url=https://web.archive.org/web/20080625161255/https://www.fda.gov/OHRMS/DOCKETS/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf |archive-date=25 June 2008 }}</ref> In 2015, a paper published in ''[[The BMJ]]'' that reanalysed the original case notes argued that in [[Study 329]],<ref name="pmid11437014">{{cite journal | vauthors = Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, Hagino OR, Koplewicz H, Carlson GA, Clarke GN, Emslie GJ, Feinberg D, Geller B, Kusumakar V, Papatheodorou G, Sack WH, Sweeney M, Wagner KD, Weller EB, Winters NC, Oakes R, McCafferty JP | title = Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 40 | issue = 7 | pages = 762–772 | date = July 2001 | pmid = 11437014 | doi = 10.1097/00004583-200107000-00010 | s2cid = 2125130 }}</ref> assessing paroxetine and [[imipramine]] against placebo in adolescents with depression, the incidence of suicidal behavior had been under-reported and the efficacy exaggerated for paroxetine.<ref name="pmid26376805">{{cite journal | vauthors = Le Noury J, Nardo JM, Healy D, Jureidini J, Raven M, Tufanaru C, Abi-Jaoude E | title = Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence | journal = BMJ | volume = 351 | article-number = h4320 | date = September 2015 | pmid = 26376805 | pmc = 4572084 | doi = 10.1136/bmj.h4320 }}</ref><ref>{{cite journal|vauthors=Godlee F |author-link=Fiona Godlee |title=Study 329 |journal=BMJ |volume=351 |article-number=h4973 |date=17 September 2015 |doi=10.1136/bmj.h4973 |doi-access=free}}</ref><ref name="pmid26377109">{{cite journal | vauthors = Doshi P | title = No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility | journal = BMJ | volume = 351 | article-number = h4629 | date = September 2015 | pmid = 26377109 | doi = 10.1136/bmj.h4629 | s2cid = 44921667 }}</ref><ref name="pmid26377210">{{cite journal | vauthors = Henry D, Fitzpatrick T | title = Liberating the data from clinical trials | journal = BMJ | volume = 351 | article-number = h4601 | date = September 2015 | pmid = 26377210 | doi = 10.1136/bmj.h4601 | s2cid = 41871189 }}</ref><ref>{{cite web| vauthors = Boseley S |url= https://www.theguardian.com/science/2015/sep/16/seroxat-study-harmful-effects-young-people |title=Seroxat study under-reported harmful effects on young people, say scientists |work=The Guardian |date=16 September 2015 |access-date=16 December 2016 |archive-url=https://web.archive.org/web/20160527025002/https://www.theguardian.com/science/2015/sep/16/seroxat-study-harmful-effects-young-people |archive-date=27 May 2016 |url-status=live}}</ref>

===Sexual dysfunction===
{{See also|Selective serotonin reuptake inhibitor#Sexual dysfunction}}
Sexual dysfunction, including loss of [[libido]], [[anorgasmia]], lack of vaginal lubrication, and erectile dysfunction, is one of the most commonly encountered adverse effects of treatment with paroxetine and other SSRIs. While early clinical trials suggested a relatively low rate of sexual dysfunction, more recent studies in which the investigator actively inquires about sexual problems suggest that the incidence is higher than 70%.<ref>{{cite journal | vauthors = Clark MS, Jansen K, Bresnahan M | title = Clinical inquiry: How do antidepressants affect sexual function? | journal = The Journal of Family Practice | volume = 62 | issue = 11 | pages = 660–661 | date = November 2013 | pmid = 24288712 }}</ref> Symptoms of sexual dysfunction have been reported to persist after discontinuing SSRIs, although this is thought to be occasional.<ref name=Csoka2008>{{cite journal | vauthors = Csoka AB, Csoka A, Bahrick A, Mehtonen OP | title = Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors | journal = The Journal of Sexual Medicine | volume = 5 | issue = 1 | pages = 227–233 | date = January 2008 | pmid = 18173768 | doi = 10.1111/j.1743-6109.2007.00630.x }}</ref><ref name=Csoka2006>{{cite journal | vauthors = Csoka AB, Shipko S | title = Persistent sexual side effects after SSRI discontinuation | journal = Psychotherapy and Psychosomatics | volume = 75 | issue = 3 | pages = 187–188 | year = 2006 | pmid = 16636635 | doi = 10.1159/000091777 | url = http://www.mediafire.com/view/hn31cmg4n28bq3x/06_pssd_Csoka.pdf | access-date = 10 January 2016 | url-status = live | s2cid = 33448116 | archive-url = https://web.archive.org/web/20160205095921/http://www.mediafire.com/view/hn31cmg4n28bq3x/06_pssd_Csoka.pdf | archive-date = 5 February 2016 }}</ref><ref>http://pi.lilly.com/us/prozac.pdf {{Webarchive|url=https://web.archive.org/web/20160303230434/http://pi.lilly.com/us/prozac.pdf |date=3 March 2016}} Page 14.</ref>

===Pregnancy===

Antidepressant exposure (including paroxetine) is associated with shorter duration of pregnancy (by three days), increased risk of preterm delivery (by 55%), lower birth weight (by {{cvt|75|g|disp=or}}), and lower [[Apgar score]]s (by <0.4 points).<ref>{{cite journal | vauthors = Ross LE, Grigoriadis S, Mamisashvili L, Vonderporten EH, Roerecke M, Rehm J, Dennis CL, Koren G, Steiner M, Mousmanis P, Cheung A | title = Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis | journal = JAMA Psychiatry | volume = 70 | issue = 4 | pages = 436–443 | date = April 2013 | pmid = 23446732 | doi = 10.1001/jamapsychiatry.2013.684 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lattimore KA, Donn SM, Kaciroti N, Kemper AR, Neal CR, Vazquez DM | title = Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis | journal = Journal of Perinatology | volume = 25 | issue = 9 | pages = 595–604 | date = September 2005 | pmid = 16015372 | doi = 10.1038/sj.jp.7211352 | doi-access = free }}</ref> The [[American College of Obstetricians and Gynecologists]] recommends that for pregnant women and women planning to become pregnant, paroxetine "be avoided, if possible", as it may be associated with increased risk of [[birth defects]].<ref name="Committee2006">{{cite journal | title = ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy | journal = Obstetrics and Gynecology | volume = 108 | issue = 6 | pages = 1601–1603 | date = December 2006 | pmid = 17138801 | doi = 10.1097/00006250-200612000-00058 | author1 = ACOG Committee on Obstetric Practice }}</ref><ref name=pmid24313569>{{cite journal | vauthors = Yonkers KA, Blackwell KA, Glover J, Forray A | title = Antidepressant use in pregnant and postpartum women | journal = Annual Review of Clinical Psychology | volume = 10 | pages = 369–392 | date = 2014 | pmid = 24313569 | pmc = 4138492 | doi = 10.1146/annurev-clinpsy-032813-153626 }}</ref>

Babies born to women who used paroxetine during the first trimester have an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects<!-- (VSDs and ASDs) -->. Unless the benefits of paroxetine justify continuing treatment, consideration should be given to stopping or switching to another antidepressant.<ref name="gsk-paxil">{{cite web|url=http://us.gsk.com/products/assets/us_paxil.pdf |archive-url=https://web.archive.org/web/20110904214137/http://us.gsk.com/products/assets/us_paxil.pdf |archive-date=4 September 2011 |title=PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: Prescribing Information |date=August 2007 |access-date=14 August 2007 |publisher=[[GlaxoSmithKline]] |location=Research Triangle Park, NC }}</ref> Paroxetine use during pregnancy is associated with about 1.5– to 1.7-fold increase in congenital birth defects, in particular, heart defects, cleft lip and palate, clubbed feet, or any birth defects.<ref name="pmid16926304">{{cite journal | vauthors = Thormahlen GM | title = Paroxetine use during pregnancy: is it safe? | journal = The Annals of Pharmacotherapy | volume = 40 | issue = 10 | pages = 1834–1837 | date = October 2006 | pmid = 16926304 | doi = 10.1345/aph.1H116 | s2cid = 28814479 }}</ref><ref name="pmid17381382">{{cite journal | vauthors = Way CM | title = Safety of newer antidepressants in pregnancy | journal = Pharmacotherapy | volume = 27 | issue = 4 | pages = 546–552 | date = April 2007 | pmid = 17381382 | doi = 10.1592/phco.27.4.546 | s2cid = 37923558 }}</ref><ref name="pmid17397101">{{cite journal | vauthors = Bellantuono C, Migliarese G, Gentile S | title = Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review | journal = Human Psychopharmacology | volume = 22 | issue = 3 | pages = 121–128 | date = April 2007 | pmid = 17397101 | doi = 10.1002/hup.836 | s2cid = 21279773 }}</ref><ref name="pmid17688379">{{cite journal | vauthors = Källén B | title = The safety of antidepressant drugs during pregnancy | journal = Expert Opinion on Drug Safety | volume = 6 | issue = 4 | pages = 357–370 | date = July 2007 | pmid = 17688379 | doi = 10.1517/14740338.6.4.357 | s2cid = 20167648 }}</ref><ref name="pmid17697910">{{cite journal | vauthors = Bar-Oz B, Einarson T, Einarson A, Boskovic R, O'Brien L, Malm H, Bérard A, Koren G | title = Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors | journal = Clinical Therapeutics | volume = 29 | issue = 5 | pages = 918–926 | date = May 2007 | pmid = 17697910 | doi = 10.1016/j.clinthera.2007.05.003 }}</ref>

===Discontinuation syndrome===
{{See also|SSRI discontinuation syndrome}}
Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Paroxetine has among the highest incidence rates and severity of withdrawal syndrome of any medication of its class.<ref name="pmid25721705">{{cite journal | vauthors = Fava GA, Gatti A, Belaise C, Guidi J, Offidani E | title = Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review | journal = Psychotherapy and Psychosomatics | volume = 84 | issue = 2 | pages = 72–81 | date = 2015 | pmid = 25721705 | doi = 10.1159/000370338 | doi-access = free }}</ref> Common withdrawal symptoms for paroxetine include nausea, dizziness, lightheadedness and vertigo; insomnia, nightmares, and vivid dreams; feelings of electricity in the body, as well as [[rebound effect|rebound depression]] and anxiety. A liquid formulation of paroxetine is available and allows a very gradual decrease of the dose, which may prevent discontinuation syndrome. Another recommendation is to temporarily switch to [[fluoxetine]], which has a longer [[half-life]] and thus decreases the severity of discontinuation syndrome.<ref name="Drug Saf2001-Haddad">{{cite journal | vauthors = Haddad PM | title = Antidepressant discontinuation syndromes | journal = Drug Safety | volume = 24 | issue = 3 | pages = 183–197 | date = March 2001 | pmid = 11347722 | doi = 10.2165/00002018-200124030-00003 | s2cid = 26897797 }}</ref><ref>{{cite journal| vauthors = Haddad PM, Anderson IM |date=November 2007 |title=Recognising and managing antidepressant discontinuation symptoms|journal=Advances in Psychiatric Treatment |volume=13 |issue=6|pages=447–457|doi=10.1192/apt.bp.105.001966 |doi-access=free}}</ref><ref>{{cite web |url=http://www.benzo.org.uk/healy.htm |title=Dependence on Antidepressants & Halting SSRIs | vauthors = Healy D |website=benzo.org.uk |access-date=23 April 2013 |archive-url=https://web.archive.org/web/20130510055900/http://benzo.org.uk/healy.htm |archive-date=10 May 2013 |url-status=live}}</ref>

In 2002, the U.S. FDA published a warning regarding "severe" discontinuation symptoms among those terminating paroxetine treatment, including paraesthesia, nightmares, and dizziness. The agency also warned of case reports describing agitation, sweating, and nausea. In connection with a Glaxo spokesperson's statement that withdrawal reactions occur only in 0.2% of patients and are "mild and short-lived", the [[IFPMA|International Federation of Pharmaceutical Manufacturers Associations]] said GSK had breached two of the federation's codes of practice.<ref name="pmid11823353">{{cite journal | vauthors = Tonks A | title = Withdrawal from paroxetine can be severe, warns FDA | journal = BMJ | volume = 324 | issue = 7332 | page = 260 | date = February 2002 | pmid = 11823353 | pmc = 1122195 | doi = 10.1136/bmj.324.7332.260 }}</ref>

Paroxetine prescribing information posted at GlaxoSmithKline has been updated related to the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.<ref name="gsk-paxil"/>

==Overdose==
Acute overdosage is often manifested by [[vomiting]], [[lethargy]], [[ataxia]], [[tachycardia]], and [[seizures]]. Plasma, serum, or blood concentrations of paroxetine may be measured to monitor therapeutic administration, confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Plasma paroxetine concentrations are generally in a range of 40–400&nbsp;μg/L in persons receiving daily therapeutic doses and 200–2,000&nbsp;μg/L in poisoned patients. Postmortem blood levels have ranged from 1–4&nbsp;mg/L in acute lethal overdose situations.<ref>{{cite journal | vauthors = Goeringer KE, Raymon L, Christian GD, Logan BK | title = Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases | journal = Journal of Forensic Sciences | volume = 45 | issue = 3 | pages = 633–648 | date = May 2000 | pmid = 10855970 | doi = 10.1520/JFS14740J }}</ref><ref>R. Baselt,''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1190–1193.</ref> Along with the other SSRIs, [[sertraline]] and [[fluoxetine]], paroxetine is considered a low-risk drug in cases of overdose.<ref>{{cite journal | vauthors = White N, Litovitz T, Clancy C | title = Suicidal antidepressant overdoses: a comparative analysis by antidepressant type | journal = Journal of Medical Toxicology | volume = 4 | issue = 4 | pages = 238–250 | date = December 2008 | pmid = 19031375 | pmc = 3550116 | doi = 10.1007/BF03161207 }}</ref>

== Interactions ==

Interactions with other drugs acting on the serotonin system or impairing the metabolism of serotonin may increase the risk of [[serotonin syndrome]] or [[neuroleptic malignant syndrome]] (NMS)-like reaction. Such reactions have been observed with SNRIs and SSRIs alone, but particularly with concurrent use of [[triptan]]s, [[Monoamine oxidase inhibitor|MAO inhibitors]], antipsychotics, or other dopamine antagonists.

The prescribing information states that paroxetine should "not be used in combination with an [[Monoamine oxidase inhibitor|MAOI]] (including linezolid, an antibiotic which is a reversible non-selective MAOI), or within 14 days of discontinuing treatment with an MAOI", and should not be used in combination with [[pimozide]], [[thioridazine]], [[tryptophan]], or [[warfarin]].<ref name="gsk-paxil"/>

Paroxetine interacts with the following [[cytochrome P450]] enzymes:<ref name = PhDep>{{cite book|title=Pharmacotherapy of Depression |year=2011 |doi=10.1007/978-1-60327-435-7 |publisher=Humana Press |isbn=978-1-60327-434-0 |edition=2nd |location=New York, NY |veditors=Ciraulo DA, Shader RI}}</ref><ref name="ReferenceA">{{cite journal | vauthors = Sanchez C, Reines EH, Montgomery SA | title = A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike? | journal = International Clinical Psychopharmacology | volume = 29 | issue = 4 | pages = 185–196 | date = July 2014 | pmid = 24424469 | pmc = 4047306 | doi = 10.1097/YIC.0000000000000023 }}</ref>
* [[CYP2D6]] for which it is both a [[Substrate (biochemistry)|substrate]] and a potent inhibitor.<ref name = TGA/><ref name="PhDep"/>
* [[CYP2B6]] (''strong'') inhibitor.
* [[CYP3A4]] (''weak'') inhibitor.
* [[CYP1A2]] (''weak'') inhibitor.
* [[CYP2C9]] (''weak'') inhibitor.
* [[CYP2C19]] (''weak'') inhibitor.

Paroxetine has been shown to be an inhibitor of [[G protein-coupled receptor kinase 2]] (GRK2).<ref name=":0" /><ref name=":1" />

==Pharmacology==
[[File:Paroxetine CYP2D6.png|class=skin-invert-image|250px|thumb|right|Mechanism of paroxetine inhibition of [[CYP2D6]]<ref name="Metabolism-guided drug design">{{cite journal|vauthors=Stepan AF, Mascitti V, Beaumont K, Kalgutkar AS |title=Metabolism-guided drug design|journal=MedChemComm|date=2013|volume=4|issue=4|page=631|doi=10.1039/C2MD20317K}}</ref>]]

===Pharmacodynamics===
Paroxetine is the most potent and one of the most specific selective [[serotonin]] (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs).<ref>{{cite journal | vauthors = Mellerup ET, Plenge P | title = High affinity binding of 3H-paroxetine and 3H-imipramine to rat neuronal membranes | journal = Psychopharmacology | volume = 89 | issue = 4 | pages = 436–439 | date = July 1986 | pmid = 2944152 | doi = 10.1007/BF02412117 | s2cid = 6037759 }}</ref> It also binds to the [[Allosteric regulation|allosteric]] site of the serotonin transporter, similarly to [[escitalopram]], though less potently so.<ref>{{cite journal | vauthors = Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N | title = Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies | journal = The International Journal of Neuropsychopharmacology | volume = 10 | issue = 1 | pages = 31–40 | date = February 2007 | pmid = 16448580 | doi = 10.1017/S1461145705006462 | doi-access = free }}</ref> Paroxetine also inhibits the reuptake of [[norepinephrine]] to a lesser extent (<50&nbsp;nmol/L).<ref>{{cite journal | vauthors = Owens JM, Knight DL, Nemeroff CB | title = [Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine] | journal = L'Encephale | volume = 28 | issue = 4 | pages = 350–355 | date = 1 August 2002 | pmid = 12232544 }}</ref> Based on evidence from four weeks of administration in rats, the equivalent of 20&nbsp;mg paroxetine taken once daily occupies approximately 88% of serotonin transporters in the [[prefrontal cortex]].<ref name="ReferenceA"/>  Paroxetine is a phenylpiperidine and might have some affinity for opioid receptors.<ref>{{cite journal | doi=10.1523/ENEURO.0063-22.2022 | title=Paroxetine Increases δ Opioid Responsiveness in Sensory Neurons | date=2022 | journal=eNeuro | volume=9 | issue=4 | pmid=35882549 | pmc=9347309 | vauthors = Brackley AD, Jeske NA | quote="Paroxetine is a phenylpiperidine and nearly all phenylpiperidines used clinically in research capacities are opioids. Interestingly, this structure is part of the morphine and fentanyl molecules. Furthermore, paroxetine-induced analgesia is dose dependently reversed by opioid receptor antagonists"}}</ref><ref>{{cite journal |title=Possible Involvement of Opioidergic and Serotonergic Mechanisms in Antinociceptive Effect of Paroxetine in Acute Pain |date=2004 |url=https://www.sciencedirect.com/science/article/pii/S1347861319325216 |journal=Journal of Pharmacological Sciences |doi=10.1254/jphs.94.161 |pmid=14978354 |access-date=8 January 2025 |volume=94 |issue=2 |pages=161–165 | vauthors = Duman EN, Kesim M, Kadioglu M, Yaris E, Kalyoncu NI, Erciyes N }}</ref>

{| class="wikitable" style="width:200px;"
|+Binding profile<ref name = GG>{{cite book|vauthors=Brunton L, Chabner B, Knollman B |title=Goodman and Gilman's The Pharmacological Basis of Therapeutics |year=2010 |publisher=McGraw-Hill Professional |isbn=978-0-07-162442-8 |edition=12th |location=New York}}</ref><ref name="ReferenceA"/><ref name="pmid11543737">{{cite journal | vauthors = Owens MJ, Knight DL, Nemeroff CB | title = Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine | journal = Biological Psychiatry | volume = 50 | issue = 5 | pages = 345–350 | date = September 2001 | pmid = 11543737 | doi = 10.1016/s0006-3223(01)01145-3 | s2cid = 11247427 }}</ref><ref name=PDSP>{{cite web|title=PDSP K<sub>i</sub> Database |website=Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth |vauthors=Roth BL, Driscol J |url=http://pdsp.med.unc.edu/pdsp.php |publisher=University of North Carolina at Chapel Hill and the United States National Institute of Mental Health |access-date=22 November 2013 |date=12 January 2011 |archive-url=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php |archive-date=8 November 2013}}</ref> Paroxetine
|-
! Receptor !! K<sub>i</sub> (nM)
|-
| [[Serotonin transporter|SERT]] || 0.07 – 0.2
|-
| [[Norepinephrine transporter|NET]] || 40 – 85
|-
| [[Dopamine transporter|DAT]] || 490
|-
| [[Dopamine receptor D2|D<sub>2</sub>]] || 7,700
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 21,200
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 6,300
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 9,000
|-
| [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] || 1,000 – 2,700
|-
| [[Alpha-2 adrenergic receptor|α<sub>2</sub>]] || 3,900
|-
| [[Muscarinic acetylcholine receptor M1|M<sub>1</sub>]] || 72
|-
| [[Histamine H1 receptor|H<sub>1</sub>]] || 13,700 – 23,700
|}

===Pharmacokinetics===
Paroxetine is well-absorbed following oral administration.<ref name="ReferenceA"/> It has an absolute [[bioavailability]] of about 50%, with evidence of a saturable [[first pass effect]].<ref name="ReferenceB">{{cite journal | vauthors = Kaye CM, Haddock RE, Langley PF, Mellows G, Tasker TC, Zussman BD, Greb WH | title = A review of the metabolism and pharmacokinetics of paroxetine in man | journal = Acta Psychiatrica Scandinavica. Supplementum | volume = 350 | pages = 60–75 | date = 1989 | pmid = 2530793 | doi = 10.1111/j.1600-0447.1989.tb07176.x | s2cid = 23769424 }}</ref> When taken orally, it achieves maximum concentration in about 6–10 hours<ref name="ReferenceA"/> and reaches steady-state in 7–14 days.<ref name="ReferenceB"/> Paroxetine exhibits significant interindividual variations in volume of distribution and clearance.<ref name="ReferenceB"/> Less than 2% of an oral dose is excreted in urine unchanged.<ref name="ReferenceB"/>

Paroxetine is a mechanism-based inhibitor of [[CYP2D6]].<ref name="Metabolism-guided drug design"/><ref name="ReferenceC">{{cite journal | vauthors = Jornil J, Jensen KG, Larsen F, Linnet K | title = Identification of cytochrome P450 isoforms involved in the metabolism of paroxetine and estimation of their importance for human paroxetine metabolism using a population-based simulator | journal = Drug Metabolism and Disposition | volume = 38 | issue = 3 | pages = 376–385 | date = March 2010 | pmid = 20007670 | doi = 10.1124/dmd.109.030551 | s2cid = 1795852 }}</ref>

[[File:Paroxetine metabolism.png|class=skin-invert-image|250px|thumb|right|Metabolism of paroxetine in humans<ref name="ReferenceC"/>]]

==Society and culture==

Paroxetine was approved for medical use in the United States in 1992 and initially sold by [[GlaxoSmithKline]].<ref name="AHFS2019" /><ref>{{cite book|url=https://books.google.com/books?id=JDZ4DAAAQBAJ&pg=PR344|title=Approved Drug Products with Therapeutic Equivalence Evaluations – FDA Orange Book 31st Edition (2011): FDA Orange Book 31st Edition (2011)|author=Food and Drug Administration|date=2011|publisher=DrugPatentWatch.com|isbn=978-1-934899-81-6|page=344|access-date=4 March 2019|archive-url=https://web.archive.org/web/20190306043352/https://books.google.ca/books?id=JDZ4DAAAQBAJ&pg=PR344|archive-date=6 March 2019|url-status=live}}</ref> It is available as a [[generic medication]].<ref name="BNF76"/> In 2022, it was the 92nd most commonly prescribed medication in the United States, with more than 7{{nbsp}}million prescriptions.<ref name="ClinCalc Top 300">{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref name="ClinCalc Paroxetine" /> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd" />

GlaxoSmithKline has paid substantial fines, paid settlements in [[Class action|class-action]] lawsuits, and become the subject of several highly critical books about its marketing of paroxetine, in particular, the [[off-label marketing]] of paroxetine for children, the suppression of negative research results relating to its use in children, and allegations that it failed to warn consumers of substantial withdrawal effects associated with the use of the drug.<ref name="JusticeDept2July2012" /><ref name="USvGSK26Oct2011" />

===Marketing===
{{See also|Study 329}}

In 2004, GSK agreed to settle charges of consumer fraud for $2.5 million.<ref>{{cite news |vauthors=Angell M |author-link=Marcia Angell |title=Drug Companies & Doctors: A Story of Corruption|newspaper=[[New York Review of Books]] |volume=56 |issue=1 |date=15 January 2009}}</ref> The [[legal discovery]] process also uncovered evidence of deliberate, systematic suppression of unfavorable Paxil research results. One of GSK's internal documents read, "It would be commercially unacceptable to include a statement that efficacy [in children] had not been demonstrated, as this would undermine the profile of paroxetine".<ref>{{cite journal | vauthors = Kondro W, Sibbald B | title = Drug company experts advised staff to withhold data about SSRI use in children | journal = CMAJ | volume = 170 | issue = 5 | page = 783 | date = March 2004 | pmid = 14993169 | pmc = 343848 | doi = 10.1503/cmaj.1040213 }}</ref>

In 2012, the [[United States Department of Justice]] fined [[GlaxoSmithKline]] $3&nbsp;billion for withholding data, unlawfully promoting use in those under 18, and preparing an article that misleadingly reported the effects of paroxetine in adolescents with depression following its clinical trial [[study 329]].<ref name=JusticeDept2July2012>{{cite press release|url=https://www.justice.gov/opa/pr/2012/July/12-civ-842.html |title=GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data |publisher=[[United States Department of Justice]], Office of Public Affairs |date=2 July 2012 |quote=The United States alleges that, among other things, GSK participated in preparing, publishing and distributing a misleading medical journal article that misreported that a clinical trial of Paxil demonstrated efficacy in the treatment of depression in patients under age 18, when the study failed to demonstrate efficacy. |access-date=6 October 2015 |archive-url=https://web.archive.org/web/20140909141736/http://www.justice.gov/opa/pr/2012/July/12-civ-842.html |archive-date=9 September 2014 |url-status=live}}</ref><ref name=USvGSK26Oct2011>{{cite court |url= https://www.justice.gov/sites/default/files/opa/legacy/2012/07/02/us-complaint.pdf |archive-url=https://web.archive.org/web/20141019043414/http://www.justice.gov/sites/default/files/opa/legacy/2012/07/02/us-complaint.pdf |archive-date=19 October 2014 |url-status=live |litigants= United States ''ex rel.'' Greg Thorpe, et al. v. GlaxoSmithKline PLC, and GlaxoSmithKline LLC |court=[[United States District Court for the District of Massachusetts|D. Mass.]] |date=26 October 2011 |pinpoint=pp.&nbsp;3–19}}</ref><ref name=ThomasNYT2July2012>{{cite news| vauthors = Thomas K, Schmidt MS |url= https://www.nytimes.com/2012/07/03/business/glaxosmithkline-agrees-to-pay-3-billion-in-fraud-settlement.html |title=Glaxo Agrees to Pay $3 Billion in Fraud Settlement |newspaper=The New York Times |date=2 July 2012 |access-date=28 February 2017 |archive-url=https://web.archive.org/web/20170302145001/http://www.nytimes.com/2012/07/03/business/glaxosmithkline-agrees-to-pay-3-billion-in-fraud-settlement.html |archive-date=2 March 2017 |url-status=live}}</ref>

In February 2016, the UK [[Competition and Markets Authority]] imposed record fines of £45 million on companies that were found to have infringed [[European Union]] and UK Competition law by entering into agreements to delay the market entry of [[Generic drug|generic]] versions of the drug in the UK. [[GlaxoSmithKline]] received the bulk of the fines, being fined £37,600,757. Other companies that produce generics were issued fines which collectively total £7,384,146. UK public health services are likely to claim damages for being overcharged in the period where the generic versions of the drug were illegally blocked from the market, as the generics are over 70% less expensive. [[GlaxoSmithKline]] may also face actions from other generic manufacturers who incurred losses as a result of the anticompetitive conduct.<ref>{{cite web|url=https://www.gov.uk/government/news/cma-fines-pharma-companies-45-million |title=CMA fines pharma companies £45 million |access-date=15 July 2016 |archive-url=https://web.archive.org/web/20160713190228/https://www.gov.uk/government/news/cma-fines-pharma-companies-45-million |archive-date=13 July 2016 |url-status=live}}</ref> In April 2016, appeals were lodged with the [[Competition Appeal Tribunal]] by the companies which were fined.<ref>{{Cite web |url=http://www.catribunal.org.uk/files/1252_GlaxoSmithKline_Summary_180416.pdf |title=GlaxoSmithKline Summary |access-date=15 July 2016 |archive-url=https://web.archive.org/web/20161012181505/http://www.catribunal.org.uk/files/1252_GlaxoSmithKline_Summary_180416.pdf |archive-date=12 October 2016 |url-status=live}}</ref><ref>{{Cite web |url=http://www.catribunal.org.uk/files/1251_Generics_Summary_180416.pdf |title=Generics Summary |access-date=15 July 2016 |archive-url=https://web.archive.org/web/20161012181518/http://www.catribunal.org.uk/files/1251_Generics_Summary_180416.pdf |archive-date=12 October 2016 |url-status=live}}</ref><ref>{{Cite web |url=http://www.catribunal.org.uk/files/1253_Xellia_Summary_180416.pdf |title=Xellia Summary |access-date=15 July 2016 |archive-url=https://web.archive.org/web/20161012181340/http://www.catribunal.org.uk/files/1253_Xellia_Summary_180416.pdf |archive-date=12 October 2016 |url-status=live}}</ref><ref>{{Cite web |url=http://www.catribunal.org.uk/files/1255_Merck_Summary_180416.pdf |title=Merck Summary |access-date=15 July 2016 |archive-url=https://web.archive.org/web/20161012181540/http://www.catribunal.org.uk/files/1255_Merck_Summary_180416.pdf |archive-date=12 October 2016 |url-status=live}}</ref><ref>{{Cite web |url=http://www.catribunal.org.uk/files/1254_Actavis_Summary_180416.pdf |title=Actavis Summary |access-date=15 July 2016 |archive-url=https://web.archive.org/web/20161012181355/http://www.catribunal.org.uk/files/1254_Actavis_Summary_180416.pdf |archive-date=12 October 2016 |url-status=live}}</ref>

GSK marketed paroxetine through television advertisements in the 1990s and 2000s. Commercials also aired for the CR version of the drug beginning in 2003.<ref>{{Cite web|url=https://adland.tv/adnews/paxil-cr-nametag-2003-30-usa |title=Paxil CR -- Nametag -- (2003) :30 (USA) &#124; Adland |date=3 April 2004 |access-date=24 February 2020 |archive-url=https://web.archive.org/web/20200224054920/https://adland.tv/adnews/paxil-cr-nametag-2003-30-usa |archive-date=24 February 2020 |url-status=live}}</ref>

===Economics===
In 2007, paroxetine was ranked 94th on the [[list of bestselling drugs]], with over $1 billion in sales. In 2006, paroxetine was the fifth-most prescribed antidepressant in the U.S. retail market, with more than 19.7 million prescriptions.<ref>The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs.{{cite web |title=Top 200 generic drugs by units in 2006. Top 200 brand-name drugs by units |website=Drug Topics, 5 March 2007 |url=http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=407652 |archive-url=https://archive.today/20130121183836/http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=407652 |archive-date=21 January 2013 |access-date=8 April 2007 }}</ref> In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S.<ref>The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs.{{cite web|title=Top 200 generic drugs by units in 2007 |website=Drug Topics |date=18 February 2008 |url=http://drugtopics.modernmedicine.com/drugtopics/Top200Drugs/ArticleStandard/article/detail/491194 |archive-url=https://web.archive.org/web/20090718184023/http://drugtopics.modernmedicine.com/drugtopics/Top200Drugs/ArticleStandard/article/detail/491194 |archive-date=18 July 2009 |access-date=23 October 2008}}</ref><ref>{{cite web |title=Top 200 brand drugs by units in 2007 |website=Drug Topics, 18 February 2008 |url=http://drugtopics.modernmedicine.com/drugtopics/PharmacyFactsAndFigures/ArticleStandard/article/detail/491210 |archive-url=https://web.archive.org/web/20090629042030/http://drugtopics.modernmedicine.com/drugtopics/PharmacyFactsAndFigures/ArticleStandard/article/detail/491210 |archive-date=29 June 2009 |access-date=23 October 2008}}</ref>

===Brand names===
Brand names include Aropax, Paretin, Brisdelle, Deroxat, Paxil,<ref name="Nevels2016">{{cite journal | vauthors = Nevels RM, Gontkovsky ST, Williams BE | title = Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required | journal = Psychopharmacology Bulletin | volume = 46 | issue = 1 | pages = 77–104 | date = March 2016 | pmid = 27738376 | pmc = 5044489 }}</ref><ref>{{cite book |title=Dictionary of Psychology |publisher=Oxford University Press | vauthors = Coleman A |year=2006 |page=552 |edition=Second}}</ref> Pexeva, Paxtine, Paxetin, Paroxat, Paraxyl,<ref>{{cite book |title=Dictionary of Psychology |publisher=Oxford University Press | vauthors = Coleman A |year=2006 |page=161 |edition=Second}}</ref> Sereupin, Daparox and Seroxat.

==Research==
Several studies have suggested that paroxetine can be used in the treatment of [[premature ejaculation]]. In particular, intravaginal ejaculation latency time (IELT) was found to increase 6- to 13-fold, which was somewhat longer than the delay achieved by the treatment with other SSRIs (fluvoxamine, fluoxetine, sertraline, and citalopram).<ref name="pmid9690692">{{cite journal | vauthors = Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B | title = Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline | journal = Journal of Clinical Psychopharmacology | volume = 18 | issue = 4 | pages = 274–281 | date = August 1998 | pmid = 9690692 | doi = 10.1097/00004714-199808000-00004 }}</ref><ref name="pmid11763001">{{cite journal | vauthors = Waldinger MD, Zwinderman AH, Olivier B | title = SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram | journal = Journal of Clinical Psychopharmacology | volume = 21 | issue = 6 | pages = 556–560 | date = December 2001 | pmid = 11763001 | doi = 10.1097/00004714-200112000-00003 | s2cid = 36888042 }}</ref><ref name="pmid15363569">{{cite journal | vauthors = Waldinger MD, Zwinderman AH, Olivier B | title = On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment | journal = European Urology | volume = 46 | issue = 4 | pages = 510–5; discussion 516 | date = October 2004 | pmid = 15363569 | doi = 10.1016/j.eururo.2004.05.005 }}</ref> However, paroxetine taken acutely ("on demand") 3–10 hours before coitus resulted only in a "clinically irrelevant and sexually unsatisfactory" 1.5-fold delay of ejaculation and was inferior to [[clomipramine]], which induced a fourfold delay.<ref name="pmid15363569"/>

There is also evidence that paroxetine may be effective in the treatment of [[compulsive gambling]]<ref>{{cite journal | vauthors = Kim SW, Grant JE, Adson DE, Shin YC, Zaninelli R | title = A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling | journal = The Journal of Clinical Psychiatry | volume = 63 | issue = 6 | pages = 501–507 | date = June 2002 | pmid = 12088161 | doi = 10.4088/JCP.v63n0606 }}</ref> and [[hot flashes]].<ref>{{cite journal | vauthors = Weitzner MA, Moncello J, Jacobsen PB, Minton S | title = A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer | journal = Journal of Pain and Symptom Management | volume = 23 | issue = 4 | pages = 337–345 | date = April 2002 | pmid = 11997203 | doi = 10.1016/S0885-3924(02)00379-2 | doi-access = free }}</ref>

Benefits of paroxetine prescription for [[diabetic neuropathy]]<ref>{{cite journal | vauthors = Sindrup SH, Gram LF, Brøsen K, Eshøj O, Mogensen EF | title = The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms | journal = Pain | volume = 42 | issue = 2 | pages = 135–144 | date = August 1990 | pmid = 2147235 | doi = 10.1016/0304-3959(90)91157-E | s2cid = 42327989 }}</ref> or chronic [[tension headache]]<ref name="pmid8132436">{{cite journal | vauthors = Langemark M, Olesen J | title = Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial | journal = Headache | volume = 34 | issue = 1 | pages = 20–24 | date = January 1994 | pmid = 8132436 | doi = 10.1111/j.1526-4610.1994.hed3401020.x | s2cid = 13715774 }}</ref> are uncertain.

Although the evidence is conflicting, paroxetine may be effective for the treatment of [[dysthymia]], a chronic disorder involving depressive symptoms for most days of the year.<ref name="pmid19017592">{{cite journal | vauthors = Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, Moore CG, Morgan L, Lohr KN | title = Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians | journal = Annals of Internal Medicine | volume = 149 | issue = 10 | pages = 734–750 | date = November 2008 | pmid = 19017592 | doi = 10.7326/0003-4819-149-10-200811180-00008 | doi-access = free }}</ref>

There is evidence to support that paroxetine selectively binds to and inhibits [[G protein-coupled receptor kinase 2]] (GRK2) in mice with heart failure. Since GRK2 regulates the activity of the beta [[adrenergic receptor]], which becomes desensitized in cases of [[heart failure]], paroxetine (or a paroxetine derivative) could be used as a heart failure treatment in the future.<ref name=":0">{{cite journal | vauthors = Thal DM, Homan KT, Chen J, Wu EK, Hinkle PM, Huang ZM, Chuprun JK, Song J, Gao E, Cheung JY, Sklar LA, Koch WJ, Tesmer JJ | title = Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility | journal = ACS Chemical Biology | volume = 7 | issue = 11 | pages = 1830–1839 | date = November 2012 | pmid = 22882301 | pmc = 3500392 | doi = 10.1021/cb3003013 }}</ref><ref name=":1">{{cite journal | vauthors = Waldschmidt HV, Homan KT, Cato MC, Cruz-Rodríguez O, Cannavo A, Wilson MW, Song J, Cheung JY, Koch WJ, Tesmer JJ, Larsen SD | title = Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine | journal = Journal of Medicinal Chemistry | volume = 60 | issue = 7 | pages = 3052–3069 | date = April 2017 | pmid = 28323425 | pmc = 5641445 | doi = 10.1021/acs.jmedchem.7b00112 }}</ref><ref>{{Cite web |title=Common antidepressant may hold key to heart failure reversal |url=https://www.sciencedaily.com/releases/2015/03/150304152607.htm |access-date=19 April 2022 |website=ScienceDaily |archive-date=5 April 2019 |archive-url=https://web.archive.org/web/20190405032837/https://www.sciencedaily.com/releases/2015/03/150304152607.htm |url-status=live }}</ref>

Paroxetine has been identified as a potential [[disease-modifying osteoarthritis drug]].<ref>{{cite journal | vauthors = Carlson EL, Karuppagounder V, Pinamont WJ, Yoshioka NK, Ahmad A, Schott EM, Le Bleu HK, Zuscik MJ, Elbarbary RA, Kamal F | title = Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis | journal = Science Translational Medicine | volume = 13 | issue = 580 | article-number = eaau8491 | date = February 2021 | pmid = 33568523 | doi = 10.1126/scitranslmed.aau8491 | s2cid = 231875553 }}</ref>

==Veterinary use==
Paroxetine may be useful in the treatment of canine or feline behavioral diagnoses and is effective in the treatment of social anxiety, depression, and agitation associated with depression.<ref>{{cite journal | vauthors = Overall KL |title=Pharmacological Treatment in Behavioural Medicine: The Importance of Neurochemistry, Molecular Biology and Mechanistic Hypotheses |journal=The Veterinary Journal |date=2001 |volume=162 |issue=1 |pages=9–23 |doi=10.1053/tvjl.2001.0568 |pmid=11409925 }}</ref>

== Other organisms ==
Paroxetine is a common finding in wastewater.<ref name="Runoff" /> It is highly toxic to the alga ''Pseudokirchneriella subcapitata'' (syn. ''[[Raphidocelis subcapitata]]'').<ref name="Runoff">
   {{Unbulleted list citebundle
      |{{*}} {{cite journal | vauthors = Chia MA, Lorenzi AS, Ameh I, Dauda S, Cordeiro-Araújo MK, Agee JT, Okpanachi IY, Adesalu AT | title = Susceptibility of phytoplankton to the increasing presence of active pharmaceutical ingredients (APIs) in the aquatic environment: A review | journal = [[Aquatic Toxicology]] | volume = 234 | article-number = 105809 | date = May 2021 | pmid = 33780670 | doi = 10.1016/j.aquatox.2021.105809 | publisher = [[Elsevier]] | bibcode = 2021AqTox.23405809C | s2cid = 232419482 }}
      |{{*}} {{cite journal | vauthors = Christensen AM, Faaborg-Andersen S, Ingerslev F, Baun A | title = Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans | journal = [[Environmental Toxicology and Chemistry]] | volume = 26 | issue = 1 | pages = 85–91 | date = January 2007 | pmid = 17269464 | doi = 10.1897/06-219R.1 | publisher = [[John Wiley & Sons, Inc.]] | s2cid = 6562531 | doi-access = free | bibcode = 2007EnvTC..26...85C }}
   }}
</ref>

It also is toxic to the soil nematode ''[[Caenorhabditis elegans]]''.<ref name="Repurposing">
   {{Unbulleted list citebundle
      |{{*}} {{cite journal | vauthors = Mangoni AA, Tuccinardi T, Collina S, Vanden Eynde JJ, Muñoz-Torrero D, Karaman R, Siciliano C, de Sousa ME, Prokai-Tatrai K, Rautio J, Guillou C, Gütschow M, Galdiero S, Liu H, Agrofoglio LA, Sabatier JM, Hulme C, Kokotos G, You Q, Gomes PA | title = Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-3 | journal = [[Molecules (journal)|Molecules]] | volume = 23 | issue = 7 | page = 1596 | date = June 2018 | pmid = 29966350 | doi = 10.3390/molecules23071596 | publisher = [[MDPI AG]] | pmc = 6099979 | s2cid = 49644934 | doi-access = free }}<!-- Published by MDPI but highly cited including by Jimenez-Lopez et al., 2020, Elmaaty et al., 2021, and Sridhar et al., 2020. -->
      |{{*}} {{cite journal | vauthors = Weeks JC, Roberts WM, Leasure C, Suzuki BM, Robinson KJ, Currey H, Wangchuk P, Eichenberger RM, Saxton AD, Bird TD, Kraemer BC, Loukas A, Hawdon JM, Caffrey CR, Liachko NF | title = Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing |journal=[[Scientific Reports]]| volume = 8 | issue = 1 | article-number = 975 | date = January 2018 | pmid = 29343694 | doi = 10.1038/s41598-017-18457-w | publisher = [[Springer Science and Business Media LLC]] | pmc = 5772060 | bibcode = 2018NatSR...8..975W | s2cid = 205636792 }}
   }}
</ref>

Alberca ''et al.'', 2016 found that paroxetine acts as a [[trypanocide]] against ''[[Trypanosoma cruzi|T. cruzi]]''.<ref name="Chagas">
{{cite journal | vauthors = Ribeiro V, Dias N, Paiva T, Hagström-Bex L, Nitz N, Pratesi R, Hecht M | title = Current trends in the pharmacological management of Chagas disease |journal=[[International Journal for Parasitology: Drugs and Drug Resistance]]| volume = 12 | pages = 7–17 | date = April 2020 | pmid = 31862616 | pmc = 6928327 | doi = 10.1016/j.ijpddr.2019.11.004 | publisher = [[Elsevier BV]] | s2cid = 209435439 }}

This review cites this study.

{{cite journal | vauthors = Alberca LN, Sbaraglini ML, Balcazar D, Fraccaroli L, Carrillo C, Medeiros A, Benitez D, Comini M, Talevi A | title = Discovery of novel polyamine analogs with anti-protozoal activity by computer-guided drug repositioning |journal=[[Journal of Computer-Aided Molecular Design]]| volume = 30 | issue = 4 | pages = 305–321 | date = April 2016 | pmid = 26891837 | doi = 10.1007/s10822-016-9903-6 | publisher = [[Springer Science and Business Media LLC]] | bibcode = 2016JCAMD..30..305A | s2cid = 25677082 }}
</ref>

Alberca ''et al.'', 2016 finds a [[leishmanicide]] effect.<ref name="computerguided"/> Alberca finds that paroxetine produces [[cell death]] of the [[promastigote]]s of ''[[Leishmania infantum|L. infantum]]''.<ref name="computerguided"/> The [[mechanism of action]] remains unknown.<ref name="computerguided">

{{cite journal | vauthors = Andrade-Neto VV, Cunha-Junior EF, Dos Santos Faioes V, Pereira TM, Silva RL, Leon LL, Torres-Santos EC | title = Leishmaniasis treatment: update of possibilities for drug repurposing | journal = Frontiers in Bioscience | volume = 23 | issue = 5 | pages = 967–996 | date = January 2018 | article-number = 4629 | pmid = 28930585 | doi = 10.2741/4629 | publisher = [[IMR Press]] }}<!-- Although a Beall's List predatory journal this review is cited by Santos et al., 2020, Carvalho et al., 2019 and Santana et al., 2021 et cetera. -->

This review cites this research.

{{cite journal | vauthors = Alberca LN, Sbaraglini ML, Balcazar D, Fraccaroli L, Carrillo C, Medeiros A, Benitez D, Comini M, Talevi A | title = Discovery of novel polyamine analogs with anti-protozoal activity by computer-guided drug repositioning | journal = Journal of Computer-Aided Molecular Design | volume = 30 | issue = 4 | pages = 305–321 | date = April 2016 | pmid = 26891837 | doi = 10.1007/s10822-016-9903-6 | publisher = [[Springer Science and Business Media LLC]] | bibcode = 2016JCAMD..30..305A | s2cid = 25677082 }}

</ref>

Various types of bacteria can break down paroxetine in the environment. These include, for example ''[[Pseudomonas|Pseudomonas sp.]]'', ''[[Bosea (bacterium)|Bosea sp.]]'', ''[[Shewanella|Shewanella sp.]], Species of [[Chitinophagaceae]] and ''[[Acinetobacter|Acinetobacter sp.]]<ref>{{Cite book |url=https://onlinelibrary.wiley.com/doi/book/10.1002/9781119678304 |title=Assessing the Microbiological Health of Ecosystems |date=19 December 2022 |publisher=Wiley |isbn=978-1-119-67832-8 | veditors = Hurst CJ |edition=1st |doi=10.1002/9781119678304}}</ref><ref>{{Cite journal | vauthors = Fernandes JP, Duarte P, Almeida CM, Carvalho MF, Mucha AP |date=August 2020 |title=Potential of bacterial consortia obtained from different environments for bioremediation of paroxetine and bezafibrate |journal=Journal of Environmental Chemical Engineering |volume=8 |issue=4 |article-number=103881 |doi=10.1016/j.jece.2020.103881}}</ref>

== References ==
{{Reflist}}

== External links ==
* {{Commons category-inline}}

{{Antidepressants}}
{{Anxiolytics}}
{{OCD pharmacotherapies}}
{{Monoamine reuptake inhibitors}}
{{Muscarinic acetylcholine receptor modulators}}
{{GlaxoSmithKline}}
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[[Category:Antidepressants]]
[[Category:Benzodioxoles]]
[[Category:CYP2B6 inhibitors]]
[[Category:CYP2D6 inhibitors]]
[[Category:4-Fluorophenyl compounds]]
[[Category:Drugs developed by GSK plc]]
[[Category:Muscarinic antagonists]]
[[Category:Phenol ethers]]
[[Category:4-Phenylpiperidines]]
[[Category:Psychiatry controversies]]
[[Category:Selective serotonin reuptake inhibitors]]
[[Category:Wikipedia medicine articles ready to translate]]