cyproheptadine

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Cyproheptadine is used to treat allergic reactions (specifically hay fever).{{cite web |url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682541.html |work = MedlinePlus Drug Information |title = Cyproheptadine |publisher = U.S. National Library of Medicine }} There is evidence supporting its use for allergies, but second generation antihistamines such as ketotifen and loratadine have shown equal results with fewer side effects.

It is also used as a preventive treatment against migraine. In a 2013 study the frequency of migraine was dramatically reduced in patients within 7 to 10 days after starting treatment. The average frequency of migraine attacks in these patients before administration was 8.7 times per month, this was decreased to 3.1 times per month at 3 months after the start of treatment.{{cite journal |vauthors = De Bruyne P, Christiaens T, Boussery K, Mehuys E, Van Winckel M |title = Are antihistamines effective in children? A review of the evidence |journal=Archives of Disease in Childhood |volume=102 |issue=1 |pages =56–60 |date = January 2017 |pmid = 27335428 |doi = 10.1136/archdischild-2015-310416 |s2cid = 21185048 }}{{cite journal |vauthors = Saito Y, Yamanaka G, Shimomura H, Shiraishi K, Nakazawa T, Kato F, Shimizu-Motohashi Y, Sasaki M, Maegaki Y |display-authors = 6 |title = Reconsideration of the diagnosis and treatment of childhood migraine: A practical review of clinical experiences |journal = Brain & Development |volume=39 |issue=5 |pages = 386–394 |date = May 2017 |pmid = 27993427 |doi=10.1016/j.braindev.2016.11.011 |s2cid=34703034 }} This use is on the label in the UK and some other countries.

It is also used off-label in the treatment of cyclical vomiting syndrome in infants; the only evidence for this use comes from retrospective studies.{{cite journal |vauthors = Salvatore S, Barberi S, Borrelli O, Castellazzi A, Di Mauro D, Di Mauro G, Doria M, Francavilla R, Landi M, Martelli A, Miniello VL, Simeone G, Verduci E, Verga C, Zanetti MA, Staiano A |display-authors = 6 |title = Pharmacological interventions on early functional gastrointestinal disorders |journal = Italian Journal of Pediatrics | volume = 42 |issue = 1 |pages = 68 |date = July 2016 |pmid = 27423188 |pmc = 4947301 |doi = 10.1186/s13052-016-0272-5 |doi-access = free }}

Cyproheptadine is sometimes used off-label to improve akathisia in people on antipsychotic medications.{{cite book |vauthors = Taylor DM, Paton C, Kapur S |title=The Maudsley Prescribing Guidelines in Psychiatry |date=2015 |publisher=John Wiley & Sons |isbn=978-1-118-75457-3 |page=85 }}

It is used off-label to treat various dermatological conditions, including psychogenic itch,{{cite journal |vauthors = Szepietowski JC, Reszke R |title = Psychogenic Itch Management |journal = Current Problems in Dermatology |volume = 50 |pages = 124–132 |year = 2016 |pmid = 27578081 |doi = 10.1159/000446055 |isbn = 978-3-318-05888-8 }} drug-induced hyperhidrosis (excessive sweating),{{cite journal |vauthors = Ashton AK, Weinstein WL |title = Cyproheptadine for drug-induced sweating |journal = The American Journal of Psychiatry |volume = 159 |issue = 5 |pages = 874–875 |date = May 2002 |pmid = 11986151 |doi = 10.1176/appi.ajp.159.5.874-a }} and prevention of blister formation for some people with epidermolysis bullosa simplex.{{cite book |vauthors = So JY, Teng J |chapter=Epidermolysis Bullosa Simplex |veditors = Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A |title=GeneReviews |date=1993 |publisher=University of Washington, Seattle |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1369/ |pmid=20301543 }}

One of the effects of the drug is increased appetite and weight gain, which has led to its use (off-label in the USA) for this purpose in children who are wasting as well as people with cystic fibrosis.{{cite web |url=https://www.vademecum.es/principios-activos-ciproheptadina%2C+estimulante+del+apetito-a15+m1 |title = Ciproheptadina, estimulante del apetito |trans-title = Cyproheptadine, appetite stimulant |work = vademecum.es |language = Spanish }}{{Cite web |url=https://www.caillon.com.uy/productos_ventana.php?id=39 |title=Bioplex NF |access-date=18 April 2018 |archive-date=18 April 2018 |archive-url=https://web.archive.org/web/20180418162117/https://www.caillon.com.uy/productos_ventana.php?id=39 |url-status=dead }}{{cite journal |vauthors = Harrison ME, Norris ML, Robinson A, Spettigue W, Morrissey M, Isserlin L |title = Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review |journal = Appetite |volume = 137 |pages = 62–72 |date=June 2019 |pmid = 30825493 |doi=10.1016/j.appet.2019.02.012 |s2cid = 72333631 }}{{cite journal |vauthors = Kim SY, Yun JM, Lee JW, Cho YG, Cho KH, Park YG, Cho B |title = Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study |journal = Clinical Therapeutics |volume = 43 |issue=10 |pages=1757–1772 |date = October 2021 |pmid=34509304 |doi = 10.1016/j.clinthera.2021.08.001 |s2cid = 237493456 }}

It is also used off-label in the management of moderate to severe cases of serotonin syndrome, a complex of symptoms associated with the use of serotonergic drugs, such as selective serotonin reuptake inhibitors (and monoamine oxidase inhibitors), and in cases of high levels of serotonin in the blood resulting from a serotonin-producing carcinoid tumor.{{cite book |veditors = Rossi S |isbn = 978-0-9805790-9-3 |title =Australian Medicines Handbook |place = Adelaide |publisher=The Australian Medicines Handbook Unit Trust |year = 2013 |edition = 2013 }}{{cite journal |vauthors = Iqbal MM, Basil MJ, Kaplan J, Iqbal MT |title = Overview of serotonin syndrome |journal = Annals of Clinical Psychiatry |volume = 24 |issue = 4 |pages = 310–318 |date = November 2012 |pmid = 23145389 }}

Cyproheptadine has sedative effects and can be used to treat insomnia similarly to other centrally-acting antihistamines.{{cite journal |vauthors=Badr B, Naguy A |title = Cyproheptadine: a psychopharmacological treasure trove? |journal=CNS Spectrums |volume = 27 |issue = 5 |pages = 533–535 |date = October 2022 |pmid = 33632345 |doi=10.1017/S1092852921000250 |doi-access = free }}{{cite journal |vauthors = Ekambaram V, Owens J |title = Medications Used for Pediatric Insomnia |journal = Child and Adolescent Psychiatric Clinics of North America |volume = 30 |issue = 1 |pages = 85–99 |date = January 2021 |pmid = 33223070 |doi=10.1016/j.chc.2020.09.001 |s2cid = 227131545 }}{{cite thesis |vauthors=Rombaut NE |year=1995 |title=Antihistamines and Sedation: Methods and Measures |id={{ProQuest|301570569}} |oclc=59660401 }}{{cite journal |vauthors = Wanderer AA, St Pierre JP, Ellis EF |title = Primary acquired cold urticaria. Double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo |journal = Archives of Dermatology |volume=113 |issue=10 |pages=1375–1377 |date=October 1977 |pmid=334082 |doi = 10.1001/archderm.113.10.1375 }} The recommended dose for this use is 4 to 8 mg.

Adverse effects include:

{{Div col}}

• Sedation and sleepiness (often transient)
• Dizziness
• Disturbed coordination
• Confusion
• Restlessness
• Excitation
• Nervousness
• Tremor
• Irritability
• Insomnia
• Paresthesias
• Neuritis
• Convulsions
• Euphoria
• Hallucinations
• Hysteria
• Faintness
• Allergic manifestation of rash and edema
• Diaphoresis
• Urticaria
• Photosensitivity
• Acute labyrinthitis
• Diplopia (seeing double)
• Vertigo
• Tinnitus
• Hypotension (low blood pressure)
• Palpitation
• Extrasystoles
• Anaphylactic shock
• Hemolytic anemia
• Blood dyscrasias such as leukopenia, agranulocytosis and thrombocytopenia
• Cholestasis
• Hepatic (liver) side effects such as:
• Hepatitis
• Jaundice
• Liver failure{{cite journal | vauthors = Chertoff J, Alam S, Clark V | title = Cyproheptadine-Induced Acute Liver Failure | journal = ACG Case Reports Journal | volume = 1 | issue = 4 | pages = 212–213 | date = July 2014 | pmid = 25580444 | pmc = 4286888 | doi = 10.14309/crj.2014.56 }}
• Hepatic function abnormality
• Epigastric distress
• Anorexia
• Nausea
• Vomiting
• Diarrhea
• Anticholinergic side effects such as:
• Blurred vision
• Constipation
• Xerostomia (dry mouth)
• Tachycardia (high heart rate)
• Urinary retention
• Difficulty passing urine
• Nasal congestion
• Nasal or throat dryness
• Urinary frequency
• Early menses
• Thickening of bronchial secretions
• Tightness of chest and wheezing
• Fatigue
• Chills
• Headache
• Increased appetite
• Weight gain

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Gastric decontamination measures such as activated charcoal are sometimes recommended in cases of overdose. The symptoms are usually indicative of CNS depression (or conversely CNS stimulation in some) and excess anticholinergic side effects. The LD₅₀ in mice is 123 mg/kg and 295 mg/kg in rats.

Cyproheptadine is a very potent antihistamine or inverse agonist of the H₁ receptor. At higher concentrations, it also has anticholinergic, antiserotonergic, and antidopaminergic activities.

Of the serotonin receptors, it is an especially potent antagonist of the 5-HT₂ receptors. This is thought to underlie its effectiveness in the treatment of serotonin syndrome.{{cite journal | vauthors = Gillman PK | title = The serotonin syndrome and its treatment | journal = Journal of Psychopharmacology | volume = 13 | issue = 1 | pages = 100–109 | date = 1999 | pmid = 10221364 | doi = 10.1177/026988119901300111 | s2cid = 17640246 | url = https://zenodo.org/record/844143 }} However, it is possible that blockade of 5-HT₁ receptors may also contribute to its effectiveness in serotonin syndrome.{{cite journal | vauthors = Sporer KA | title = The serotonin syndrome. Implicated drugs, pathophysiology and management | journal = Drug Safety | volume = 13 | issue = 2 | pages = 94–104 | date = August 1995 | pmid = 7576268 | doi = 10.2165/00002018-199513020-00004 | s2cid = 19809259 }} Cyproheptadine has been reported to block 85% of 5-HT₂ receptors in the human brain at a dose of 4 mg three times per day (12 mg/day total) and to block 95% of 5-HT₂ receptors in the human brain at a dose of 6 mg three times per day (18 mg/day total) as measured with positron emission tomography (PET).{{cite journal | vauthors = Kapur S, Zipursky RB, Jones C, Wilson AA, DaSilva JD, Houle S | title = Cyproheptadine: a potent in vivo serotonin antagonist | journal = The American Journal of Psychiatry | volume = 154 | issue = 6 | pages = 884a–884 | date = June 1997 | pmid = 9167527 | doi = 10.1176/ajp.154.6.884a | doi-access = }} The dose of cyproheptadine recommended to ensure blockade of the 5-HT₂ receptors for serotonin syndrome is 20 to 30 mg.

Blockade of the serotonin 5-HT_2B receptor may be specifically involved in the antimigraine effects of cyproheptadine.{{cite journal | vauthors = Segelcke D, Messlinger K | title = Putative role of 5-HT2B receptors in migraine pathophysiology | journal = Cephalalgia | volume = 37 | issue = 4 | pages = 365–371 | date = April 2017 | pmid = 27127104 | doi = 10.1177/0333102416646760 | url = }}

Besides its activity at neurotransmitter targets, cyproheptadine has been reported to possess weak antiandrogenic activity.{{cite journal | vauthors = Pucci E, Petraglia F | title = Treatment of androgen excess in females: yesterday, today and tomorrow | journal = Gynecological Endocrinology | volume = 11 | issue = 6 | pages = 411–433 | date = December 1997 | pmid = 9476091 | doi = 10.3109/09513599709152569 }}

Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours.{{cite book | vauthors = Murray L, Daly F, McCoubrie DM, Cadogan M | title = Toxicology Handbook | url = https://books.google.com/books?id=KDOeIldGWxQC&pg=PT388 | access-date = 27 November 2011 | date = 15 January 2011 | publisher = Elsevier Australia | isbn = 978-0-7295-3939-5 | page = 388}} Its terminal half-life when taken orally is approximately 8 hours.

Cyproheptadine is a tricyclic benzocycloheptene and is closely related to pizotifen and ketotifen as well as to tricyclic antidepressants.

Cyproheptadine was studied in one small trial as an adjunct in people with schizophrenia whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from.{{cite journal |vauthors = Buoli M, Altamura AC |title = May non-antipsychotic drugs improve cognition of schizophrenia patients? |journal = Pharmacopsychiatry |volume = 48 |issue = 2 |pages = 41–50 |date = March 2015 |pmid = 25584772 |doi = 10.1055/s-0034-1396801 |s2cid = 19202816 }} It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect.

There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by selective serotonin reuptake inhibitor (SSRI) and antipsychotic medications.{{cite journal |vauthors = Nunes LV, Moreira HC, Razzouk D, Nunes SO, Mari J |title = Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review |journal = Journal of Sex & Marital Therapy |volume = 38 |issue = 3 |pages = 281–301 |date = 2012 |pmid = 22533871 |doi = 10.1080/0092623X.2011.606883 |s2cid = 23406005 }}

Cyproheptadine has been studied for the treatment of post-traumatic stress disorder.{{cite journal |vauthors = Dabaghzadeh F, Khalili H, Ghaeli P, Dashti-Khavidaki S |title = Potential benefits of cyproheptadine in HIV-positive patients under treatment with antiretroviral drugs including efavirenz |journal = Expert Opinion on Pharmacotherapy |volume = 13 |issue = 18 |pages = 2613–2624 |date = December 2012 |pmid = 23140169 |doi=10.1517/14656566.2012.742887 |s2cid=25769557 }}

Cyproheptadine is used in cats as an appetite stimulant{{cite journal | vauthors = Agnew W, Korman R | title = Pharmacological appetite stimulation: rational choices in the inappetent cat | journal = Journal of Feline Medicine and Surgery | volume = 16 | issue = 9 | pages = 749–756 | date = September 2014 | pmid = 25146662 | doi = 10.1177/1098612X14545273 | s2cid = 37126352 | pmc = 11185246 }}{{cite book | edition=2 | year=2012 | publisher=Academic Press | publication-place=Amsterdam Boston | veditors = Gupta RC | title=Veterinary Toxicology : Basic and Clinical Principles | isbn=978-0-12-385926-6 | oclc=794491298 | pages=xii+1438}}{{rp|page=1371}} and as an adjunct in the treatment of asthma.{{cite book |vauthors= Dowling PM |chapter= Systemic Therapy of Airway Disease: Cyproheptadine |chapter-url= http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/190907.htm |veditors= Kahn CM, Line S, Aiello SE |title= The Merck Veterinary Manual |date= 8 February 2005 |publisher= John Wiley & Sons |edition= 9th |isbn= 978-0-911910-50-6 |archive-date= 4 March 2016 |access-date= 26 October 2008 |archive-url= https://web.archive.org/web/20160304072415/http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm%2Fbc%2F190907.htm |url-status= dead }} Retrieved on 26 October 2008. Possible adverse effects include excitement and aggressive behavior.{{cite book |vauthors= Dowling PM |chapter= Drugs Affecting Appetite |chapter-url= http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/190302.htm |veditors= Kahn CM, Line S, Aiello SE |title= The Merck Veterinary Manual |date= 8 February 2005 |publisher= John Wiley & Sons |edition= 9th |isbn= 978-0-911910-50-6 |title-link= Merck Veterinary Manual |archive-date= 28 October 2012 |access-date= 26 October 2008 |archive-url= https://web.archive.org/web/20121028205743/http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm%2Fbc%2F190302.htm |url-status= dead }} Retrieved on 26 October 2008. The elimination half-life of cyproheptadine in cats is 12 hours.

Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses.{{cite journal | vauthors = Durham AE | title = Therapeutics for Equine Endocrine Disorders | journal = The Veterinary Clinics of North America. Equine Practice | volume = 33 | issue = 1 | pages = 127–139 | date = April 2017 | pmid = 28190613 | doi = 10.1016/j.cveq.2016.11.003 }}{{cite web | vauthors = Kritchevsky JE | date = July 2019 | work = Merck Vet Manual|title=Hirsutism Associated with Adenomas of the Pars Intermedia|url=https://www.merckvetmanual.com/endocrine-system/the-pituitary-gland/hypertrichosis-associated-with-adenomas-of-the-pars-intermedia |access-date=24 April 2011}}

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