Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study

Abstract

Purpose: Cyproheptadine, an antihistamine and antiserotonergic agent, is an appetite stimulant that is efficacious in promoting weight gain in children and adults with poor appetite. Despite numerous studies showing that cyproheptadine achieved positive outcomes, studies documenting its effectiveness on appetite are limited. This study evaluated the efficacy and tolerability of cyproheptadine in adults with poor appetite in South Korea. Methods: Patients aged 19 to 64 years with poor appetite were randomly assigned to receive either cyproheptadine or placebo for 8 weeks. The primary end point was the difference between the groups in change in appetite, as measured by the Korean version of the Edmonton Symptom Assessment System from the beginning to the end of the study period. The secondary end points included effects on weight, anthropometrics, body composition, Simplified Nutritional Appetite Questionnaire-measured appetite, and toxicities. A total of 375 patients were randomly assigned to the two groups (189 cyproheptadine, 186 placebo). Findings: The cyproheptadine group experienced a mean (SD) change in appetite score of -2.42 (0.12) compared with -2.03 (0.13) in the placebo arm, representing a statistically significant appetite gain in the cyproheptadine group (difference, + 0.38 [0.18]; 95% CI, -0.73 to -0.04; P = 0.0307). Patients in the cyproheptadine group experienced significant increases in weight and body mass index. The most common adverse event was somnolence, as predicted. Cyproheptadine was well tolerated, with one serious adverse event (colitis) which was classified as a moderate adverse effect unlikely to be related to the study drug. Implications: We present the largest randomized, double-blind, placebo-controlled clinical trial of cypro-heptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cypro-heptadine. Cyproheptadine is a safe treatment option in patients with poor appetite. Our findings provide important information for the use of cyproheptadine to ameliorate poor appetite in adults. Further randomized studies focused on the effect of cyproheptadine in older populations are needed. (Clin Ther. 2021;43:1757- 1767.) (c) 2021 Elsevier Inc.