Cyproheptadine, sold under the brand name Periactin among others, is a first-generationantihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.
It was patented in 1959 and came into medical use in 1961.[5]
Cyproheptadine's 3D molecular structure represented as Space-filling model
Cyproheptadine is used to treat allergic reactions (specifically hay fever).[6] The evidence for its use for this purpose indicates its effectiveness but second generation antihistamines such as ketotifen and loratadine have shown equal results with fewer side effects.[7]
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.[7][8] 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.[9]
Cyproheptadine is sometimes used off-label to improve akathisia in people on antipsychotic medications.[10]
It used off-label to treat various dermatological conditions, including psychogenic itch[11] drug-induced hyperhidrosis (excessive sweating),[12] and prevention of blister formation for some people with epidermolysis bullosa simplex.[13]
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.[14][15][16]
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.[17][18]
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.[3][4]
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, and this underlies its effectiveness in the treatment of serotonin syndrome.
Cyproheptadine is known to be an antagonist or inverse agonist of all of the receptors listed in the adjacent table.[20]
Cyproheptadine has weak antiandrogenic activity.[21]
Pharmacokinetics[]
Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours.[22] Its terminal half-life when taken orally is approximately 8 hours.[2]
Chemistry[]
Cyproheptadine is a tricyclicbenzocycloheptene and is closely related to pizotifen and ketotifen as well as to tricyclic antidepressants.
Research[]
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.[23] 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.[24]
There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by SSRI and antipsychotic medications.[25]
Cyproheptadine has been studied for the treatment of posttraumatic stress disorder.[24]
Veterinary use[]
Cyproheptadine is used in cats as an appetite stimulant[26] and as an adjunct in the treatment of asthma.[27] Possible adverse effects include excitement and aggressive behavior.[28] The elimination half-life of cyproheptadine in cats is 12 hours.[27]
Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses.[29][30]
^ Jump up to: abGunja N, Collins M, Graudins A (2004). "A comparison of the pharmacokinetics of oral and sublingual cyproheptadine". Journal of Toxicology. Clinical Toxicology. 42 (1): 79–83. doi:10.1081/clt-120028749. PMID15083941. S2CID20196551.
^ Jump up to: abDe Bruyne, P; Christiaens, T; Boussery, K; Mehuys, E; Van Winckel, M (January 2017). "Are antihistamines effective in children? A review of the evidence". Archives of Disease in Childhood. 102 (1): 56–60. doi:10.1136/archdischild-2015-310416. PMID27335428. S2CID21185048.
^Saito, Y; Yamanaka, G; Shimomura, H; Shiraishi, K; Nakazawa, T; Kato, F; Shimizu-Motohashi, Y; Sasaki, M; Maegaki, Y (May 2017). "Reconsideration of the diagnosis and treatment of childhood migraine: A practical review of clinical experiences". Brain & Development. 39 (5): 386–394. doi:10.1016/j.braindev.2016.11.011. PMID27993427. S2CID34703034.
^Szepietowski, JC; Reszke, R (2016). Psychogenic Itch Management. Current Problems in Dermatology. 50. pp. 124–32. doi:10.1159/000446055. ISBN978-3-318-05888-8. PMID27578081.
^Harrison ME, Norris ML, Robinson A, Spettigue W, Morrissey M, Isserlin L (2019). "Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review". Appetite. 137: 62–72. doi:10.1016/j.appet.2019.02.012. PMID30825493. S2CID72333631.CS1 maint: uses authors parameter (link)
^Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN978-0-9805790-9-3.
^ Jump up to: abRoth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
^Pucci E, Petraglia F (December 1997). "Treatment of androgen excess in females: yesterday, today and tomorrow". Gynecol. Endocrinol. 11 (6): 411–33. doi:10.3109/09513599709152569. PMID9476091.
^Lindsay Murray; Frank Daly; David McCoubrie; Mike Cadogan (15 January 2011). Toxicology Handbook. Elsevier Australia. p. 388. ISBN978-0-7295-3939-5. Retrieved 27 November 2011.
^Buoli, M; Altamura, AC (March 2015). "May non-antipsychotic drugs improve cognition of schizophrenia patients?". Pharmacopsychiatry. 48 (2): 41–50. doi:10.1055/s-0034-1396801. PMID25584772.
^ Jump up to: abDabaghzadeh, F; Khalili, H; Ghaeli, P; Dashti-Khavidaki, S (December 2012). "Potential benefits of cyproheptadine in HIV-positive patients under treatment with antiretroviral drugs including efavirenz". Expert Opinion on Pharmacotherapy. 13 (18): 2613–24. doi:10.1517/14656566.2012.742887. PMID23140169. S2CID25769557.
^Nunes, LV; Moreira, HC; Razzouk, D; Nunes, SO; Mari Jde, J (2012). "Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review". Journal of Sex & Marital Therapy. 38 (3): 281–301. doi:10.1080/0092623X.2011.606883. PMID22533871. S2CID23406005.
^Agnew, W; Korman, R (September 2014). "Pharmacological appetite stimulation: rational choices in the inappetent cat". Journal of Feline Medicine and Surgery. 16 (9): 749–56. doi:10.1177/1098612X14545273. PMID25146662. S2CID37126352.
^Dowling PM (February 8, 2005). "Drugs Affecting Appetite". In Kahn CM, Line S, Aiello SE (eds.). The Merck Veterinary Manual (9th ed.). John Wiley & Sons. ISBN978-0-911910-50-6. Retrieved on October 26, 2008.
^Durham, AE (April 2017). "Therapeutics for Equine Endocrine Disorders". The Veterinary Clinics of North America. Equine Practice. 33 (1): 127–139. doi:10.1016/j.cveq.2016.11.003. PMID28190613.