Abstract
Cancer related anorexia and cachexia significantly impair nutritional status, quality of life, and treatment outcomes. While appetite stimulants like megestrol acetate and dronabinol have shown effectiveness, their adverse effects limit long-term use. Cyproheptadine, a first-generation antihistamine and serotonin antagonist, has emerged as a potentially safer alternative. This review aims to evaluate critically synthesize previous research findingson clinical studies, randomized trials, and retrospective analyses on cyproheptadine’s efficacy and safety as an appetite stimulant. It has shown consistent benefits across various populations, including children with cystic fibrosis, patients with nonorganic failure to thrive, and adults with cancer-related cachexia. Improvements include significant appetite score increases (e.g., K-ESAS change of –2.42 vs. –2.03 with placebo; p = 0.0307), average weight gains of ~24 g/day, and improved BMI and nutritional markers such as albumin and hemoglobin. The most common side effect was mild drowsiness, while serious adverse effects like hepatotoxicity were rare. However, concerns remain about off-label overuse in community settings, often due to lack of patient education and regulatory oversight. Overall, cyproheptadine appears to be an effective and well-tolerated short-term option for appetite stimulation. Nonetheless, more research is needed to establish long-term safety, efficacy, and appropriate dosing guidelines.
References
Alssageer M, Alsahref A, Abdelqader M. Characteristics, perspectives, and experiences of cyproheptadine users at community pharmacies in the context to prescription medication misuse. AlQalam J Med Appl Sci. 2024;1165-73. doi:10.54361/ajmas.247437
Chansane S, Suntornsantoon W, Chaiyapak P, Thet D, Siritientong T. A retrospective study of body weight changes in patients receiving cyproheptadine in a hospital-based outpatient setting in Thailand. Indones J Pharm. 2023. doi:10.22146/ijp.5776.
Cho YG, Cho B, Cho KH, Kim SY, Lee JW, Park YG, et al. Efficacy and tolerability of cyproheptadine in poor appetite: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2021;43(12):2117-25. doi:10.1016/j.clinthera.2021.08.001.
Couluris M, Mayer JL, Freyer DR, Sandler E, Xu P, Krischer JP. The effect of cyproheptadine hydrochloride (Periactin) and megestrol acetate (Megace) on weight in children with cancer/treatment-related cachexia. J Pediatr Hematol Oncol. 2008;30(11):791-7.
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011 May;12(5):489-95. doi:10.1016/S1470-2045(10)70218-7.
Grunert J, van der Haak N, La Vanda C, Farrow N, Tai A. Cyproheptadine as an appetite stimulant in children with cystic fibrosis. Clin Nutr ESPEN. 2021;42:407-9. doi:10.1016/j.clnesp.2021.01.015.
Gupta M, Gupta N, Madabushi J. Off-label cyproheptadine in children and adolescents: psychiatric comorbidities, interacting variables, safety, and risks of hepatotoxicity. Cureus. 2023;15(1):e33745. doi:10.7759/cureus.33745.
Hassan YH, Abdelbary NM, Alhassanin SA, Ahmed ME, Gohar SF. Role of cyproheptadine as appetite stimulant in cancer associated anorexia. Menoufia Med J. 2024;37(3). doi:10.59204/2314-6788.3260.
Homnick DN, Homnick BD, Reeves AJ, Marks JH, Pimentel RS, Bonnema SK. Cyproheptadine hydrochloride is an effective appetite stimulant in cystic fibrosis. Pediatr Pulmonol. 2004;38(2):129-34.
Kazemi SA, Khosravi Yekta M, Fallah R, Diaz D, Eftekhari K. Evaluation of cyproheptadine hydrochloride effects on weight gain in underweight children with anorexia; a randomized clinical trial. J Pediatr Perspect. 2017;5(12):6413-9.
Laviano A, Koverech A. Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Curr Opin Clin Nutr Metab Care. 2020;23(6):450-4.
Lin YC, Yen HR, Tsai FJ, Wang CH, Chien LC, Chen AC, Lin RT. Effects of cyproheptadine on body weight gain in children with nonorganic failure to thrive in Taiwan: a hospital-based retrospective study. PLoS One. 2021;16(10):e0258731. doi:10.1371/journal.pone.0258731.
Mohammadi MR, Mostafavi SA, Hosseinzadeh P, Nojoumi M, Asadian-Koohestani F. Comparing the effects of folic acid and cyproheptadine on appetite, weight, and ADHD symptoms in children with ADHD: a randomized clinical trial. J Iran Med Counc. 2021. doi:10.18502/jimc.v4i4.8473.
Najib K, Moghtaderi M, Karamizadeh Z, Fallahzadeh E. Beneficial effect of cyproheptadine hydrochloride on body mass index in undernourished children: a randomized controlled trial. Iran J Pediatr. 2014;24:753-8.
Rerksuppaphol S, Rerksuppaphol L. Effect of cyproheptadine hydrochloride on weight gain in malnourished children: a randomized, controlled trial. Asian Biomed. 2010;4:977-82.
Saleh S. Misuse of appetite-stimulant drugs in Babylon. Iraqi J Pharm Sci. 2012;21(2):31-4.
Soliman HH, Minton SE, Khushalani NI, Lush RM, Geyer SJ, Copur MS. A pilot study of cyproheptadine in advanced cancer patients with anorexia. J Clin Oncol. 2021;39.
World Health Organization (WHO). Clinical disorders arising from dietary affluence in countries of the Eastern Mediterranean Region: situation analysis and guidelines for control. WHO Regional Office for the Eastern Mediterranean. 1990. Publication No. 14.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 Shabrina Adinda Septiarani, Arya Gading Purwanto, Vivi Septiani Putri, Nabilah Siti Zahara, Alisha Dian Prasasti, Karina Insanillahiya, Kannaya Sabriena Keenan Iswanto, Aisyah Humairah, Primayanti Nurul Ilmi