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Cyproheptadine for ADHD

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Cyproheptadine for ADHD

1. Mechanisms of action of cyproheptadine

Cyproheptadine is a1

  • H1 antihistamine
  • Serotonin HT2 receptor antagonist
  • anticholinergic
  • blocks hypothalamic centers
    • thereby inhibits the release of cortisol

Plasma half-life: 6 to 9 hours

2. Indications for use of cyproheptadine

Cyproheptadine is used:

  • Loss of appetite (only in veterinary medicine and without veterinary marketing authorization)
  • Anorexia nervosa (no marketing authorization)
  • Hives (cold urticaria) (drug approval in Germany only for this, and only if conventional antihistamines are not sufficient)
  • Antiallergic (USA only)
    • seasonal allergic or vasomotor rhinitis
    • allergic conjunctivitis
    • allergic skin symptoms
    • Improvement of the allergic reaction to blood or plasma
    • Dermographism (“made hives”, urticaria factitia)

3. Side effects and contraindications of cyproheptadine

Side effects of cyproheptadine21

  • Fatigue, drowsiness
  • central Disorders
  • Visual disturbances
  • Digestive disorders
  • Urinary retention
  • dry mucous membranes
  • increased appetite
  • Hypersensitivity
  • Pain, headaches
  • Cramps
  • Shock, shivering, dizziness, sweating
  • allergic skin reactions, exanthema
  • Drowsiness, somnolence, hallucinations
  • Mydriasis, narrow-angle glaucoma, visual disturbances
  • Dry mouth
  • Micturition disorders
  • Cardiac arrhythmia, tachycardia
  • Blood count changes
  • Disorders of the gastrointestinal tract

Contraindications of cyproheptadine21

  • Hypersensitivity to cyproheptadine
  • Bladder emptying disorders
  • Narrow-angle glaucoma
  • acute asthma attack
  • Pregnancy, breastfeeding
  • Children
  • Infants
  • Infants
  • Breastfeeding
  • Simultaneous treatment with an MAO inhibitor
  • Stomach or intestinal ulcer
  • Prostate enlargement
  • Urinary retention
  • Intestinal obstruction

4. Cyproheptadine for weight gain in humans

A systematic review on the use of cyproheptadine for weight gain found significant weight gain in 39 of 46 studies analyzed. In contrast, in malignant/progressive diseases, such as HIV and cancer, there was barely any benefit of cyproheptadine. The most common side effect was transient mild to moderate sedation. The review concluded that cyproheptadine is a safe and generally well-tolerated drug for weight gain.3
A recent larger RCT also found cyproheptadine to be an effective and safe medication for weight gain in adults.4

Another systematic review on the safety of cyproheptadine found a total of 93 adverse effects in the French pharmacovigilance database from 1985 to 2020 (adults 81.7%, children 18.3%)5
These were primarily

  • neurological symptoms (n = 38, adults 71 %, children 28.9 %)
  • hepatic complications (n = 15, adults 86.7 %, children 13.3 %; 0.27 to 1.4/1000, independent of age)

Cyproheptadine was thus classified as a safe medicinal product. To be on the safe side, it was not recommended for use in small children. The liver values should be checked.

5. Cyproheptadine for weight gain in ADHD

A number of people with ADHD report problems with loss of appetite due to stimulant use. In individual cases, this goes so far that stimulant treatment has to be discontinued, even though they have good effects on ADHD symptoms.

Cyproheptadine is an option for appetite problems when taking stimulants6
A person with ADHD (36 kg) reported that 10 ml of cyproheptadine successfully corrected her appetite reduction caused by stimulants.

However, a study on the preventive effect of 1 to 12 mg cyproheptadine on sleep and appetite problems caused by methylphenidate in 40 children aged 2 to 12 years found no differences compared to the placebo group.7

It should only be used to increase appetite in ADHD under close medical supervision. Liver values should be monitored when using cyproheptadine, as very rare cases of liver failure have been reported.


  1. Cyproheptadin, DocCheck Flexikon, abgerufen 15.09.22

  2. Cyproheptadin bei pharmawiki.ch

  3. Harrison, Norris, Robinson, Spettigue, Morrissey, Isserlin (2019): Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review. Appetite. 2019 Jun 1;137:62-72. doi: 10.1016/j.appet.2019.02.012. PMID: 30825493.) REVIEW

  4. Kim SY, Yun JM, Lee JW, Cho YG, Cho KH, Park YG, Cho B (2021): Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study. Clin Ther. 2021 Oct;43(10):1757-1772. doi: 10.1016/j.clinthera.2021.08.001. PMID: 34509304. n = 375

  5. Bertrand, Massy, Vegas, Gras, Chalouhi, Tavolacci, Abadie (2021): Safety of Cyproheptadine, an Orexigenic Drug. Analysis of the French National Pharmacovigilance Data-Base and Systematic Review. Front Pediatr. 2021 Sep 29;9:712413. doi: 10.3389/fped.2021.712413. PMID: 34676184; PMCID: PMC8525494. REVIEW

  6. Stutzman DL, Dopheide JA (2024): Practice Pearls for Stimulant Treatment of Attention-Deficit/Hyperactivity Disorder in Youth. J Pediatr Pharmacol Ther. 2024 Jun;29(3):215-231. doi: 10.5863/1551-6776-29.3.215. PMID: 38863854; PMCID: PMC11163912.

  7. Kadkhoda Mezerji, Moharreri, Mohammadpour, Elyasi (2019): Preventive effect of cyproheptadine on sleep and appetite disorders induced by methylphenidate: an exploratory randomised, double-blinded, placebo-controlled clinical trial. Int J Psychiatry Clin Pract. 2019 Mar;23(1):72-79. doi: 10.1080/13651501.2018.1509095. PMID: 30261781. n = 40

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