Antipruritic

2025-10-25T05:26:03Z

2600:6C44:42F0:9560:C7:F1FE:B9DD:7BC5: Antidepressants aren’t considered abirritants

{{Short description|Medications that inhibit itching}}
'''Antipruritics''', '''abirritants''',<ref>{{Cite web|title=Antipruritic definition and meaning {{!}} Collins English Dictionary|url=https://www.collinsdictionary.com/dictionary/english/antipruritic|access-date=2021-03-25|website=www.collinsdictionary.com|language=en}}</ref> or '''anti-itch drugs''', are [[medication]]s that inhibit [[itch]]ing (Latin: ''[[pruritus]]'').
Itching is often associated with [[sunburn]]s, [[allergic reaction]]s, [[eczema]], [[psoriasis]], [[chickenpox]], [[Fungal infection in animals|fungal infection]]s, [[insect bites and stings]] like those from [[mosquito]]es, [[flea]]s, [[mite]]s, and [[contact dermatitis]] and [[urticaria]] caused by plants such as [[poison ivy]] ([[urushiol-induced contact dermatitis]]) or [[Urtica dioica|stinging nettle]]. Itching can also be caused by [[chronic kidney disease]] and related conditions.<ref>{{cite web
| last = Butler
| first = David F.
| publisher = [[Medscape]]
|date=2020-12-11|title=Pruritus and Systemic Disease: Background, Pathophysiology, Etiology|url=https://emedicine.medscape.com/article/1098029-overview#:~:text=Pruritus,%20or%20itch,%20is%20most,,%20dermatitis%20herpetiformis,%20or%20pemphigoid.}}</ref>

Abirritants consist of a large group of drugs belonging to different classes with varying mechanisms to treat [[itch]]. They may work either directly or indirectly to relieve itch, and evidence on their effectiveness varies from one class to another.<ref name=":0">{{cite journal | vauthors = Simonsen E, Komenda P, Lerner B, Askin N, Bohm C, Shaw J, Tangri N, Rigatto C | display-authors = 6 | title = Treatment of Uremic Pruritus: A Systematic Review | journal = American Journal of Kidney Diseases | volume = 70 | issue = 5 | pages = 638–655 | date = November 2017 | pmid = 28720208 | doi = 10.1053/j.ajkd.2017.05.018 | doi-access = free }}</ref> Some alternative medicines are also used to treat itch.<ref name=":10">{{cite journal | vauthors = Shi ZF, Song TB, Xie J, Yan YQ, Du YP | title = The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | journal = Evidence-Based Complementary and Alternative Medicine | volume = 2017 | article-number = 6026434 | date = 2017 | pmid = 28713436 | pmc = 5497608 | doi = 10.1155/2017/6026434 | doi-access = free }}</ref><ref name=":11">{{cite journal | vauthors = Tabassum N, Hamdani M | title = Plants used to treat skin diseases | journal = Pharmacognosy Reviews | volume = 8 | issue = 15 | pages = 52–60 | date = January 2014 | pmid = 24600196 | pmc = 3931201 | doi = 10.4103/0973-7847.125531 | doi-access = free }}</ref> Side effects of abirritants also vary depending on the class of the drug. Even before the emergence of modern [[evidence-based medicine]], abirritants had already been used in many civilizations, but practices and choice of drugs differ by [[culture]].<ref name=":3">{{cite journal | vauthors = Weisshaar E, Grüll V, König A, Schweinfurth D, Diepgen TL, Eckart WU | title = The symptom of itch in medical history: highlights through the centuries | journal = International Journal of Dermatology | volume = 48 | issue = 12 | pages = 1385–94 | date = December 2009 | pmid = 20415680 | doi = 10.1111/j.1365-4632.2009.04117.x | s2cid = 28909284 }}</ref>

== Types ==
A number of drug classes are available as abirritants for itching relief, but there is no one single specific abirritant to treat all forms of itch.<ref name=":4">{{cite book | vauthors = Yosipovitch G | chapter = Pruritus|date=2009 | title =Dermatological Signs of Internal Disease|pages=75–79|publisher=Elsevier|language=en|doi=10.1016/b978-1-4160-6111-3.00015-x|isbn=978-1-4160-6111-3 }}</ref> Treatments may vary depending on the cause. Commonly prescribed abirritants can be broadly divided into [[Topical medication|topical]] and [[Systemic drug|systemic]] drugs, and may include a combination of one or more drugs, described as below.

===Topical===
[[File:Tube of Hydrocortison, Oude Pekela (2019) 02.jpg|thumb|183x183px|Corticosteroid creams can be applied directly on the skin to treat itch.]]
[[Topical medication|Topical]] formulations are preferred for treating localized itch caused by skin damage, inflammation or dryness.<ref name=":8">{{cite journal | vauthors = Yosipovitch G | title = Assessment of itch: more to be learned and improvements to be made | journal = The Journal of Investigative Dermatology | volume = 121 | issue = 6 | pages = xiv-xv | date = December 2003 | pmid = 14675224 | doi = 10.1111/j.1523-1747.2003.12650.x | doi-access = free }}</ref> Topical antipruritics in the form of [[cream (pharmaceutical)|cream]]s and [[spray (liquid drop)|spray]]s are often available [[Over-the-counter drugs|over the counter]]. The [[active ingredient]]s usually belong to these classes:
* [[Antihistamine]]s such as [[diphenhydramine]] (Benadryl) and [[hydroxyzine]]
* [[Corticosteroid]]s such as [[hydrocortisone]] topical cream, see [[topical steroid]]
* [[Counterirritant]]s, such as [[Mentha|mint oil]], [[menthol]], or [[camphor]]<ref name="Hercogova">{{cite journal |author=Hercogová J |title=Topical anti-itch therapy |journal=Dermatologic Therapy |volume=18 |issue=4 |pages=341–3 |year=2005 |pmid=16297007 |doi=10.1111/j.1529-8019.2005.00033.x|s2cid=31573591 |doi-access=free }}</ref>
* [[Local anesthetic]]s such as [[lidocaine]], [[pramoxine]], or [[benzocaine]] in topical creams or lotions

{| class="wikitable"
|+
!Medication
!Mechanism of Action
!Examples
|-
|[[Corticosteroid]]s
|Suppresses itch originating from immune response and inflammation<ref name=":14">{{cite journal | vauthors = Norris DA | title = Mechanisms of action of topical therapies and the rationale for combination therapy | journal = Journal of the American Academy of Dermatology | volume = 53 | issue = 1 Suppl 1 | pages = S17-25 | date = July 2005 | pmid = 15968260 | doi = 10.1016/j.jaad.2005.04.027 }}</ref>
|
* [[Betamethasone]]
* [[Hydrocortisone]]
|-
|[[Antihistamine]]s
|Antihistamines have anti-inflammatory properties that can relieve itching by suppressing the underlying inflammation<ref name=":13">{{cite book | vauthors = Buddenkotte J, Maurer M, Steinhoff M | title = Histamine in Inflammation | chapter = Histamine and Antihistamines in Atopic Dermatitis | series = Advances in Experimental Medicine and Biology | volume = 709 | pages = 73–80 | date = 2010 | pmid = 21618889 | doi = 10.1007/978-1-4419-8056-4_8 | publisher = Springer US | isbn = 978-1-4419-8055-7 | place = Boston, MA | veditors = Thurmond RL }}</ref>
|
* First generation: [[Chlorphenamine]] and [[diphenhydramine]]
* Second generation: [[Fexofenadine]]
|-
|[[Anesthetic]]s
|Prevents the propagation of nerve signals that would otherwise cause an itching sensation<ref name=":16">{{cite journal | vauthors = Rinaldi G | title = The Itch-Scratch Cycle: A Review of the Mechanisms | journal = Dermatology Practical & Conceptual | volume = 9 | issue = 2 | pages = 90–97 | date = April 2019 | pmid = 31106010 | pmc = 6502296 | doi = 10.5826/dpc.0902a03 }}</ref>
|
* [[Pramocaine|Pramoxine]]
* [[Lidocaine/prilocaine]]
|-
|[[Phosphodiesterase-4 inhibitor]]s
|Suppresses inflammation to relieve itch<ref name=":16" />
|
* [[Roflumilast]]
* [[Crisaborole]]
|-
|[[Capsaicin]]
| colspan="2" |Desensitizes nerves that cause itch<ref name=":8" />
|}

=== Systemic drugs ===
[[File:A strip of antihistamine.jpg|thumb|Antihistamines are commonly used to treat itching associated with allergies.]]
Generalized itch, or itching across the whole body, can be a symptom of a dermatological disorder or an underlying systemic problem.<ref name=":25">{{Cite journal| vauthors = Reamy BV, Bunt CW, Fletcher S |date=2011-07-15|title=A Diagnostic Approach to Pruritus|url=https://www.aafp.org/afp/2011/0715/p195.html|journal=American Family Physician|volume=84|issue=2|pages=195–202|pmid=21766769|issn=0002-838X}}</ref> Some systemic diseases can that cause generalized itch include [[diabetes]], [[hypothyroidism]], [[kidney disease]]s and [[liver disease]]s.<ref>{{cite journal | vauthors = Kantor GR, Lookingbill DP | title = Generalized pruritus and systemic disease | language = English | journal = Journal of the American Academy of Dermatology | volume = 9 | issue = 3 | pages = 375–82 | date = September 1983 | pmid = 6630598 | doi = 10.1016/S0190-9622(83)70144-1 }}</ref><ref name=":25" /> It is usually treated with systemic agents instead of topical agents.<ref>{{Cite book| vauthors = Freedberg IM, Sanchez MR |title=Current dermatologic diagnosis & treatment|date=2001|publisher=Current Medicine|isbn=1-57340-172-2|oclc=45129566}}</ref> Corticosteroids and antihistamines mentioned above can also be used to treat generalized itch.<ref>{{cite journal | vauthors = Yosipovitch G, Bernhard JD | title = Clinical practice. Chronic pruritus | journal = The New England Journal of Medicine | volume = 368 | issue = 17 | pages = 1625–34 | date = April 2013 | pmid = 23614588 | doi = 10.1056/NEJMcp1208814 | s2cid = 1912215 }}</ref> Common systemic abirritants are listed below:
[[File:Gabapentin.jpg|thumb|315x315px|Gabapentin is an [[anticonvulsant]] which can also be used to treat itch.]]
{| class="wikitable"
|+
!Medication
!Mechanism of Action
!Examples
|-
|Corticosteroids
|Suppresses itch originating from immune response and inflammation<ref name=":14" />
|
* [[Betamethasone]]
* [[Hydrocortisone]]
|-
|Antihistamines
|Antihistamines have anti-inflammatory properties that can relieve itching by suppressing the underlying inflammation<ref name=":13" /><ref>{{cite web |last1=Stöppler |first1=Melissa Conrad |title=Itch (Itching or Pruritus) |url=https://www.medicinenet.com/itch/article.htm#what_should_i_know_about_itching |website=MedicineNet |access-date=3 June 2019}}</ref>
|
* First generation: [[Chlorphenamine]] and [[diphenhydramine]]
* Second generation: [[Fexofenadine]]
|-
|[[μ-opioid receptor]] antagonists
|Blocks the μ-opioid receptor, the stimulation of which causes itch in clinical settings such as [[Cholestatic pruritus|itch due to liver diseases]]<ref name=":5">{{cite journal | vauthors = Phan NQ, Bernhard JD, Luger TA, Ständer S | title = Antipruritic treatment with systemic μ-opioid receptor antagonists: a review | journal = Journal of the American Academy of Dermatology | volume = 63 | issue = 4 | pages = 680–8 | date = October 2010 | pmid = 20462660 | doi = 10.1016/j.jaad.2009.08.052 }}</ref>
|
* [[Naloxone]]
* [[Naltrexone]]
* [[Nalmefene]]
|-
|Antidepressants
|Reduces itch by mediating [[serotonin]] and [[histamine]] levels in the body.<ref name=":15">{{cite journal | vauthors = Patel T, Yosipovitch G | title = Therapy of pruritus | journal = Expert Opinion on Pharmacotherapy | volume = 11 | issue = 10 | pages = 1673–82 | date = July 2010 | pmid = 20426711 | pmc = 2885583 | doi = 10.1517/14656566.2010.484420 }}</ref>
|Two main classes of antidepressants are utilized to relieve itch:
* [[Atypical antidepressant]]s acting on histamine receptors can useful in itching that occurs at night. An example is [[mirtazapine]]<ref name=":15" />
* [[Selective serotonin reuptake inhibitor|Selective serotinin reuptake inhibitors]] (SSRIs) are often used in psychiatric patients with itching. Common SSRIs include [[fluoxetine]] and [[sertraline]]<ref name=":15" />
|-
|Immunosuppressants
|Suppresses the immune system to reduce inflammation and hence reduce itch<ref>{{cite journal | vauthors = Schmitt J, Schmitt N, Meurer M | title = Cyclosporin in the treatment of patients with atopic eczema - a systematic review and meta-analysis | journal = Journal of the European Academy of Dermatology and Venereology | volume = 21 | issue = 5 | pages = 606–19 | date = May 2007 | pmid = 17447974 | doi = 10.1111/j.1468-3083.2006.02023.x | s2cid = 34610971 }}</ref>
|
* [[Ciclosporin|Cyclosporin]]
|-
|Anticonvulsants
|Mechanism of action is unclear, but is thought to prevent itching by desensitizing [[calcium channel]]s in nerves<ref>{{cite journal | vauthors = Matsuda KM, Sharma D, Schonfeld AR, Kwatra SG | title = Gabapentin and pregabalin for the treatment of chronic pruritus | journal = Journal of the American Academy of Dermatology | volume = 75 | issue = 3 | pages = 619–625.e6 | date = September 2016 | pmid = 27206757 | doi = 10.1016/j.jaad.2016.02.1237 }}</ref>
|
* [[Gabapentin]]
* [[Pregabalin]]
|-
|[[Thalidomide]]
| colspan="2" |Thalidomide suppresses itching through a number of ways:
* Acts as a [[Depressant|central depressant]];
* Reduces inflammation;
* Modulates immune response; and
* Modulates nerve signal transmission<ref name=":18">{{cite journal | vauthors = Sharma D, Kwatra SG | title = Thalidomide for the treatment of chronic refractory pruritus | journal = Journal of the American Academy of Dermatology | volume = 74 | issue = 2 | pages = 363–9 | date = February 2016 | pmid = 26577510 | doi = 10.1016/j.jaad.2015.09.039 }}</ref>
|-
|[[Butorphanol]]
| colspan="2" |Butorphanol activates the '''[[κ-opioid receptor]]''' and blocks the μ-opioid receptor, inhibiting generalized pruritus due to an imbalance between the μ- and κ-opioid systems
|}

Oral antipruritics are usually [[prescription drug]]s. Those more recently described include:
* [[Nalfurafine]], a centrally-acting [[κ-opioid receptor]] [[agonist]] approved for [[uremic pruritus]] and effective in [[animal model]]s of other prurituses<ref name="Inui2015">{{cite journal|last1=Inui|first1=Shigeki|title=Nalfurafine hydrochloride to treat pruritus: a review|journal=Clinical, Cosmetic and Investigational Dermatology|year=2015|pages=249–55|issn=1178-7015|doi=10.2147/CCID.S55942|pmc=4433050|pmid=26005355|volume=8 |doi-access=free }}</ref>
* [[Oclacitinib]], a [[janus kinase inhibitor]] used to control pruritus in dogs.

==Substances proposed to act antipruritically, but not used medically==
* [[Burow's solution]], an astringent aqueous solution of [[aluminium triacetate]], is shown to soothe and to relieve itching.<ref>{{Cite web |title=CFR - Code of Federal Regulations Title 21 |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=347.52 |archive-url=https://web.archive.org/web/20060929094208/http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=347.52 |archive-date=September 29, 2006 |access-date=2022-07-28 |website=www.accessdata.fda.gov}}</ref>
* [[Olive oil]]
* [[Jewelweed]] has been shown to be devoid of any anti-itch activity in several controlled studies.<ref>{{cite journal | last1 = Long | first1 = D. | last2 = Ballentine | first2 = N. H. | last3 = Marks | first3 = J. G. | title = Treatment of poison ivy/oak allergic contact dermatitis with an extract of jewelweed. | journal = Am. J. Contact. Dermat | volume = 8 | issue = 3| pages = 150–3 | pmid = 9249283 | date = September 1997 | doi = 10.1097/01206501-199709000-00005 }}</ref><ref>{{cite journal | last1 = Gibson | first1 = M. R. | last2 = Maher | first2 = F. T. | title = Activity of jewelweed and its enzymes in the treatment of Rhus dermatitis. | journal = J. Am. Pharm. Assoc. | volume = 39 | issue = 5| pages = 294–6 | pmid = 15421925 | date = May 1950 | doi = 10.1002/jps.3030390516 }}</ref><ref>{{cite journal | last1 = Guin | first1 = J. D. | last2 = Reynolds | first2 = R. | title = Jewelweed treatment of poison ivy dermatitis. | journal = Contact Dermatitis | volume = 6 | issue = 4| pages = 287–8 | pmid = 6447037 | date = June 1980 | doi = 10.1111/j.1600-0536.1980.tb04935.x | s2cid = 46551170 }}</ref><ref>{{cite journal|last=Zink |first=B. J. |author2=Otten, E.J. |author3=Rosenthal, M. |author4=Singal, B |title=The Effect Of Jewel Weed In Preventing Poison Ivy Dermatitis |journal=Journal of Wilderness Medicine |volume=2 |issue=3 |pages=178–182 |year=1991 |url=http://www.wemjournal.org/wmsonline/?request=get-abstract&issn=0953-9859&volume=002&issue=03&page=0178 |access-date=2008-01-16 |doi=10.1580/0953-9859-2.3.178 |s2cid=57162394 |url-access=subscription }}{{dead link|date=July 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
* [[Calamine lotion]], containing [[zinc oxide]] and [[iron(III) oxide]], is a traditional remedy for mild itching, such as that typically associated with chicken pox – although the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] has asserted that it has little if any scientific evidence.<ref>{{cite web |url=http://www.iht.com/articles/1992/09/09/topi.php |title=American Topics. An Outdated Notion, That Calamine Lotion |access-date=2007-07-19 | archive-url= https://web.archive.org/web/20070619004539/http://www.iht.com/articles/1992/09/09/topi.php| archive-date= 19 June 2007 | url-status= live}}</ref><ref>{{cite journal | last1 = Appel | first1 = L.M. Ohmart | last2 = Sterner | first2 = R.F. | year = 1956 | title = Zinc oxide: A new, pink, refractive microform crystal | journal = AMA Arch Dermatol | volume = 73 | issue = 4 | pages = 316–324 | doi = 10.1001/archderm.1956.01550040012003 | pmid = 13301048 }}</ref> Nevertheless, they subsequently recommended applying topical OTC skin protectants, such as calamine, to relieve the itch caused by poisonous plants such as [[poison ivy]], [[poison oak]], and [[poison sumac]].<ref>[https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm049342.htm September 2, 2008 FDA Document] {{webarchive|url=https://web.archive.org/web/20100716055654/https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm049342.htm |date=July 16, 2010 }}</ref>
* Paste of [[sodium bicarbonate]] (baking soda) and water, applied topically<ref name="Paul Tawrell 2008">Paul Tawrell, ''Wilderness Camping and Hiking''(Falcon Distribution, 2008), 212.</ref>
* [[Ammonium hydroxide]] (household ammonia), applied topically<ref name="Paul Tawrell 2008"/>
* [[Papain]]-based topical creams.

=== Alternative treatments ===
A number of herbs have been used to treat itching such as [[cannabis]], [[Portulaca oleracea|pigweed]] (''Portulaca oleracaea''), [[Saraca asoca|ashoka]] (''Saraca asoca''), and [[Common fig|fig]] (''Ficus carica'').<ref name=":11" />

Other unconventional forms of treatment with potential efficacy for treating systemic itch include topical [[cannabinoid]]s<ref>{{cite journal | vauthors = Baswan SM, Klosner AE, Glynn K, Rajgopal A, Malik K, Yim S, Stern N | title = Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders | journal = Clinical, Cosmetic and Investigational Dermatology | volume = 13 | pages = 927–942 | date = December 2020 | pmid = 33335413 | pmc = 7736837 | doi = 10.2147/CCID.S286411 | doi-access = free }}</ref> and H4 [[antihistamine]]s.<ref>{{Cite journal|date=August 1980|journal=InPharma|volume=251|issue=1|pages=3–4|doi=10.1007/bf03317207|issn=0156-2703|title=New Histamine H2-Receptor Antagonists Are on the Way|s2cid=198228678}}</ref>

== Effectiveness ==
Despite the availability of many forms of treatment, there is only a limited number of case series or small-scale studies examining the efficacy of abirritants.<ref name=":15" /> There is a lack of evidence on treatment for chronic pruritus of unknown origin.<ref>{{cite journal | vauthors = Andrade A, Kuah CY, Martin-Lopez JE, Chua S, Shpadaruk V, Sanclemente G, Franco JV | title = Interventions for chronic pruritus of unknown origin | journal = The Cochrane Database of Systematic Reviews | volume = 1 | article-number = CD013128 | date = January 2020 | issue = 1 | pmid = 31981369 | pmc = 6984650 | doi = 10.1002/14651858.CD013128.pub2 | collaboration = Cochrane Skin Group }}</ref><ref name=":6">{{cite journal | vauthors = Millington GW, Collins A, Lovell CR, Leslie TA, Yong AS, Morgan JD, Ajithkumar T, Andrews MJ, Rushbook SM, Coelho RR, Catten SJ, Lee KY, Skellett AM, Affleck AG, Exton LS, Mohd Mustapa MF, Levell NJ | display-authors = 6 | title = British Association of Dermatologists' guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018 | journal = The British Journal of Dermatology | volume = 178 | issue = 1 | pages = 34–60 | date = January 2018 | pmid = 29357600 | doi = 10.1111/bjd.16117 | doi-access = free }}</ref> There is also little to no evidence on the efficacy and safety of using abirritants during [[pregnancy]].<ref>{{cite journal | vauthors = Rungsiprakarn P, Laopaiboon M, Sangkomkamhang US, Lumbiganon P | title = Pharmacological interventions for generalised itching (not caused by systemic disease or skin lesions) in pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | article-number = CD011351 | date = February 2016 | issue = 2 | pmid = 26891962 | doi = 10.1002/14651858.CD011351.pub2 | pmc = 8665832 | collaboration = Cochrane Pregnancy and Childbirth Group }}</ref>

=== Treating itch associated with disease ===
Some abirritants work by indirectly treating itch through treating the causative medical conditions, which means that the itching associated with the condition will often subside when it is properly treated. This includes [[antihistamine]]s and [[corticosteroid]]s, which are effective in treating inflammatory disorders of the skin, in particular atopic dermatitis.<ref>{{cite journal | vauthors = Wahlgren CF | title = Itch and atopic dermatitis: an overview | journal = The Journal of Dermatology | volume = 26 | issue = 11 | pages = 770–9 | date = November 1999 | pmid = 10635621 | doi = 10.1111/j.1346-8138.1999.tb02090.x | s2cid = 20259978 }}</ref> Successful treatment of atopic dermatitis with either corticosteroids or antihistamines would resolve the associated itching.<ref name=":7">{{cite journal | vauthors = Coondoo A, Phiske M, Verma S, Lahiri K | title = Side-effects of topical steroids: A long overdue revisit | journal = Indian Dermatology Online Journal | volume = 5 | issue = 4 | pages = 416–25 | date = October 2014 | pmid = 25396122 | pmc = 4228634 | doi = 10.4103/2229-5178.142483 | doi-access = free }}</ref>

=== Treating itch directly ===
Some abirritants treat pruritus directly without necessarily treating the causative medical condition. Abirritants that directly treat itching and are established to be effective are reported here in the table below:
{| class="wikitable"
|+
!Medication
!Effectiveness
|-
|[[Gabapentin]]
|Gabapentin was found to be effective in decreasing the severity of [[uremic pruritus]] compared to placebo.<ref>{{cite journal | vauthors = Eusebio-Alpapara KM, Castillo RL, Dofitas BL | title = Gabapentin for uremic pruritus: a systematic review of randomized controlled trials | journal = International Journal of Dermatology | volume = 59 | issue = 4 | pages = 412–422 | date = April 2020 | pmid = 31777066 | doi = 10.1111/ijd.14708 | s2cid = 208335862 }}</ref>
|-
|[[Butorphanol]]
|Continuous intravenous butorphanol reduced the incidence of [[morphine]]-induced pruritus significantly.<ref name=":17">{{cite journal | vauthors = Du BX, Song ZM, Wang K, Zhang H, Xu FY, Zou Z, Shi XY | title = Butorphanol prevents morphine-induced pruritus without increasing pain and other side effects: a systematic review of randomized controlled trials | journal = Canadian Journal of Anaesthesia | volume = 60 | issue = 9 | pages = 907–17 | date = September 2013 | pmid = 23813290 | doi = 10.1007/s12630-013-9989-4 | doi-access = free }}</ref>
|-
|[[Thalidomide]]
|Thalidomide is effective in treating chronic refractory pruritus among patients who had failed conventional therapy (corticosteroids or antihistamines), with a 50% or greater reduction in symptoms and a shorter time to improvement.<ref name=":18" />
|-
|μ-opioid receptor antagonists
|μ-opioid receptor antagonists such as naltrexone and nalmefene demonstrated significant improvement in treating patients with [[Cholestatic pruritus|cholestatic]] pruritus, or itch arising from [[Hives|urticaria]] and atopic dermatitis.<ref name=":5" />
|}

=== Traditional Chinese medicine ===
[[File:Dictamnus_albus_SLO.jpg|thumb|178x178px|[[Dictamnus]] is one of the many herbs used to treat itch in Traditional Chinese Medicine.]]
[[Traditional Chinese medicine]] is extensively used in Asia for relief of itch. It is believed that itching is caused by irritations from wind, dampness or blood stasis, and can be relieved by the use of herbs such as [[chrysanthemum]], [[Gardenia|gardenia fruit]] or [[mung bean]].<ref>{{Cite web|title=Chinese Herbal Selections for Itchy Conditions|url=http://www.shen-nong.com/eng/exam/chinese_herbal_selections_for_itchy_conditions.html|access-date=2021-03-25|website=www.shen-nong.com}}</ref> Sometimes these herbal remedies are used in combination with [[acupuncture]] and [[moxibustion]],<ref name=":10" /> but their efficacy is still unclear.<ref>{{Cite Q|Q134734579}}</ref> [[Sericin]] cream and oral [[omega-3 fatty acid]] supplements may show benefit in reducing itch.<ref name=":6" />

== Adverse effects ==
Each class of abirritants has its own set of potential adverse effects.

=== Systemic corticosteroids ===
[[File:CushingsFace.jpg|alt=Fat tissue deposits on the sides of the face causes the patient's face to have a rounded appearance.|thumb|Systemic corticosteroid treatment can cause redistribution of fat tissue, leading to [[moon face]].<ref name=":1">{{cite journal | vauthors = Poetker DM, Reh DD | title = A comprehensive review of the adverse effects of systemic corticosteroids | journal = Otolaryngologic Clinics of North America | volume = 43 | issue = 4 | pages = 753–68 | date = August 2010 | pmid = 20599080 | doi = 10.1016/j.otc.2010.04.003 }}</ref>]]
Systemic corticosteroid use has been associated with a wide range of potential adverse effects. In a review article, the following common complications were noted for prolonged use: redistribution of fat tissues ([[moon face]]), [[Hyperglycemia|high blood sugar]], infections, delayed wound healing, and [[HPA axis suppression]], where the body's natural production of hormones like [[corticotropin-releasing hormone]] and [[adrenocorticotropic hormone]] is suppressed as a response to the increased level of corticosteroids in the blood.<ref name=":1" />

There is a lack of data on adverse effects associated with corticosteroid use of a shorter period and lower dose.<ref name=":1" />

=== Topical corticosteroids ===
Both local and systemic side effects can result from topical corticosteroid use, especially in prolonged treatment.<ref name=":7" />

Local side effects can occur regularly from prolonged use,<ref name=":2">{{cite journal | vauthors = Hengge UR, Ruzicka T, Schwartz RA, Cork MJ | title = Adverse effects of topical glucocorticosteroids | language = English | journal = Journal of the American Academy of Dermatology | volume = 54 | issue = 1 | pages = 1–15; quiz 16–8 | date = January 2006 | pmid = 16384751 | doi = 10.1016/j.jaad.2005.01.010 }}</ref> which include skin atrophy (thinning), [[stretch marks]], infections, lighter skin color, and [[Tachyphylaxis|sudden decrease in efficacy of the drug]].<ref name=":7" /><ref name=":2" />

Systemic side effects are far less prevalent than local ones.<ref name=":2" /> Prolonged high potency corticosteroids use on thin skin, especially in children, increases the risk of systemic side effects since thin skin allows for greater absorption.<ref name=":19">{{cite journal | vauthors = Dhar S, Seth J, Parikh D | title = Systemic side-effects of topical corticosteroids | journal = Indian Journal of Dermatology | volume = 59 | issue = 5 | pages = 460–4 | date = September 2014 | pmid = 25284850 | pmc = 4171913 | doi = 10.4103/0019-5154.139874 | doi-access = free }}</ref> One commonly cited systemic side effect from topical use is [[HPA axis suppression]].<ref name=":19" /> A meta-analysis of topical corticosteroid use in children concluded that low-potency corticosteroid at recommended dosages and duration do not cause clinically significant HPA suppression.<ref name=":21">{{cite journal | vauthors = Wood Heickman LK, Davallow Ghajar L, Conaway M, Rogol AD | title = Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis | journal = Hormone Research in Paediatrics | volume = 89 | issue = 6 | pages = 389–396 | date = 2018 | pmid = 29898449 | doi = 10.1159/000489125 | doi-access = free }}</ref>

=== Antihistamines ===
Antihistamines target the molecule histamine by blocking the [[histamine H1 receptor]].<ref name=":20">{{cite journal | vauthors = Simons FE | title = Advances in H1-antihistamines | journal = The New England Journal of Medicine | volume = 351 | issue = 21 | pages = 2203–17 | date = November 2004 | pmid = 15548781 | doi = 10.1056/NEJMra033121 }}</ref> First-generation antihistamines like [[diphenhydramine]] and [[chlorpheniramine]] are able to move from the blood into the brain across the [[blood–brain barrier]], where they block the H1 receptor, reducing the neurotransmitter effect of histamine, leading to central nervous system side effects such as drowsiness and confusion.<ref name=":20" /> Second generation antihistamines, such as fexofenadine and [[cetirizine]] are less able to move from blood circulation into the brain and are therefore associated with fewer side effects in usual doses.<ref name=":20" />

=== μ-Opioid receptor antagonists ===
μ-opioid receptor antagonists are usually well-tolerated and have no abuse potential since they do not cause physical dependence.<ref name=":5" /> Side effects are dose-dependent and generally limited to the first two weeks of treatment.<ref>{{cite journal | vauthors = Dixon R, Gentile J, Hsu HB, Hsiao J, Howes J, Garg D, Weidler D | title = Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist | journal = Journal of Clinical Pharmacology | volume = 27 | issue = 3 | pages = 233–9 | date = March 1987 | pmid = 3680580 | doi = 10.1002/j.1552-4604.1987.tb02191.x | s2cid = 25620439 }}</ref><ref>{{cite journal | vauthors = Metze D, Reimann S, Beissert S, Luger T | title = Efficacy and safety of naltrexone, an oral opiate receptor antagonist, in the treatment of pruritus in internal and dermatological diseases | language = English | journal = Journal of the American Academy of Dermatology | volume = 41 | issue = 4 | pages = 533–9 | date = October 1999 | pmid = 10495371 | doi = 10.1016/S0190-9622(99)80048-6 }}</ref><ref>{{cite journal | vauthors = Bergasa NV, Alling DW, Talbot TL, Swain MG, Yurdaydin C, Turner ML, Schmitt JM, Walker EC, Jones EA | display-authors = 6 | title = Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial | journal = Annals of Internal Medicine | volume = 123 | issue = 3 | pages = 161–7 | date = August 1995 | pmid = 7598296 | doi = 10.7326/0003-4819-123-3-199508010-00001 | s2cid = 36396897 }}</ref> [[Opioid withdrawal]] symptoms are rare and may include severe [[lightheadedness]], [[depersonalization]] and [[anxiety]].<ref name=":5" />

=== Immunosuppressants ===
Immunosuppressants may cause [[immunodeficiency]], resulting in an increased susceptibility to infection. Other side effects include bone marrow suppression, increased risk of cardiovascular disease and increased risk of cancer.<ref name=":23">{{Cite journal| vauthors = Hsu DC, Katelaris CH |date=2009-06-01|title=Long-term management of patients taking immunosuppressive drugs |journal=Australian Prescriber|volume=32|issue=3|pages=68–71|doi=10.18773/austprescr.2009.035|issn=0312-8008|doi-access=free}}</ref>

=== Capsaicin ===
Being the main chemical that causes heat in [[chili pepper]], the main side effect of capsaicin is a burning sensation that usually persists for several days. A topical anaesthetic can be used to reduce the sensation. In addition, the topical anaesthetic can also provide anti-itch effect on its own.<ref name=":24">{{cite book | vauthors = Leslie TA, Greaves MW, Yosipovitch G | title = Pharmacology of Itch | chapter = Current topical and systemic therapies for itch | series = Handbook of Experimental Pharmacology | volume = 226 | pages = 337–56 | date = 2015 | pmid = 25861788 | doi = 10.1007/978-3-662-44605-8_18 | publisher = Springer Berlin Heidelberg | isbn = 978-3-662-44604-1 | veditors = Cowan A, Yosipovitch G | place = Berlin, Heidelberg }}</ref>

== History ==
[[File:Scilla_cilicica_-_Taurus_Squill_04.jpg|thumb|[[Squill]] was used to treat itch and is commonly listed in ancient pharmacopeia.]]
Abirritants have an extensive history in treating itch. The history of abirritants dates back to the [[Byzantine Empire|Byzantine]] period, when [[Alexander of Tralles|Alexander of Tralleis]], a famous physician, recommended crushed [[rue]] and [[alum]] mixed in honey for topical application to the scalp for itching caused by scabby conditions of the head.<ref name=":3" />

During the 7th century, [[Paul of Aegina]], a famous [[Greeks|Greek]] physician, described a list of drugs for treatment of itch including plants such as the [[squill]], metallic components, and goat droppings which were applied externally. These drugs are common in ancient [[Pharmacopoeia|pharmacopeia]].<ref>{{cite journal | vauthors = Er U, Naderi S | title = Paulus aegineta: review of spine-related chapters in "Epitomoe medicoe libri septem" | journal = Spine | volume = 38 | issue = 8 | pages = 692–5 | date = April 2013 | pmid = 23026871 | doi = 10.1097/brs.0b013e3182760fa0 | s2cid = 205518726 }}</ref>

The ''[[Lorsch Pharmacopoeia]]'' written in the [[Lorsch monastery|monastery of Lorsch]] in the 8th century described many preparations of abirritants for both systemic and topical use, such as an ointment prepared from stinging [[Nettle|nettle seeds]].<ref>{{Cite journal| vauthors = Brevart FB |date=June 1994|title=Das "Lorscher Arzneibuch": Ein medizinisches Kompendium des 8. Jahrhunderts (Codex Bambergensis medicinalis 1): Text, Ubersetzung und Fachglossar. Ulrich Stoll|journal=Isis|volume=85|issue=2|pages=314–315|doi=10.1086/356835|issn=0021-1753}}</ref>

[[Mercury (element)|Mercury]]-coated girdles were used in the 17th century as an expensive treatment to alleviate symptoms of itch caused by [[scabies]], but mercury toxins in the blood often caused other troubling symptoms in patients.<ref>{{cite journal | vauthors = Puza CJ, Suresh V | title = Scabies and Pruritus-A Historical Review | journal = JAMA Dermatology | volume = 154 | issue = 5 | page = 536 | date = May 2018 | pmid = 29801071 | doi = 10.1001/jamadermatol.2018.0147 }}</ref>

In the 20th century, many new abirritants for external use emerged, including [[salicylic acid]]s, [[naphthol]], [[tar]], [[Carbolic Acid|carbolic acid]], [[thymol]], and [[menthol]], which were mostly available in the form of ointments. [[Alcohols (medicine)|Alcohol]] and [[opium]] were also commonly prescribed.<ref name=":3" />

== See also ==
* [[Itch]]ing
* [[Atopic dermatitis]]

== References ==
{{Reflist|2}}

== External links ==
* {{cite journal | year = 2006 | title = Frontiers in pruritus research: scratching the brain for more effective itch therapy| url= | journal = Journal of Clinical Investigation| volume = 116 | issue = 5| pages = 1174–1185 | doi = 10.1172/JCI28553 | pmid = 16670758| last1 = Paus | first1 = R. | pmc = 1451220}}

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[[Category:Antipruritics]]

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