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

  • Author Footnotes
    † These authors contributed equally to this work as first authors.
    Sue Youn Kim
    Footnotes
    † These authors contributed equally to this work as first authors.
    Affiliations
    Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
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  • Author Footnotes
    † These authors contributed equally to this work as first authors.
    Jae Moon Yun
    Footnotes
    † These authors contributed equally to this work as first authors.
    Affiliations
    Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
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  • Ji-Won Lee
    Affiliations
    Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
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  • Young Gyu Cho
    Affiliations
    Department of Family Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, South Korea
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  • Kyung-Hwan Cho
    Affiliations
    Department of Family Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
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  • Author Footnotes
    ‡ These authors contributed equally to this work as corresponding authors.
    Yong Gyu Park
    Footnotes
    ‡ These authors contributed equally to this work as corresponding authors.
    Affiliations
    Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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  • Author Footnotes
    ‡ These authors contributed equally to this work as corresponding authors.
    Belong Cho
    Correspondence
    Address correspondence to: Belong Cho MD, PhD, Department of Family Medicine, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul, 03080, South Korea.
    Footnotes
    ‡ These authors contributed equally to this work as corresponding authors.
    Affiliations
    Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    † These authors contributed equally to this work as first authors.
    ‡ These authors contributed equally to this work as corresponding authors.
Published:September 08, 2021DOI:https://doi.org/10.1016/j.clinthera.2021.08.001

      Highlights

      • Cyproheptadine is a safe appetite stimulant in patients with poor appetite.
      • Patients administered with the cyproheptadine experienced significant increases in weight and body mass index.
      • The most common side effect was drowsiness and cyproheptadine was well tolerated with few serious adverse events.

      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 cyproheptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cyproheptadine. 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.

      Key words

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