Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.

[8] 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 off-label in the treatment of cyclical vomiting syndrome in infants; the only evidence for this use comes from retrospective studies.

[12] It is used off-label to treat various dermatological conditions, including psychogenic itch,[13] drug-induced hyperhidrosis (excessive sweating),[14] and prevention of blister formation for some people with epidermolysis bullosa simplex.

[15] 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.

[31] 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).

[33] Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours.