Cyproheptadine for ADHD

• 1. Mechanisms of action of cyproheptadine
• 2. Indications for cyproheptadine
• 3. Side effects and contraindications of cyproheptadine
• 4. Cyproheptadine for weight gain in humans
• 5. Cyproheptadine for weight gain in 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 cyproheptadine¶

Cyproheptadine is used:

• Loss of appetite (only in veterinary medicine and without veterinary drug approval)
• Anorexia nervosa (no drug approval)
• 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 allergic reaction to blood or plasma
  • Dermographism (“made hives”, urticaria factitia)

3. Side effects and contraindications of cyproheptadine¶

Side effects of Cyproheptadine²¹

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

Contraindications to cyproheptadine²¹

• Hypersensitivity to cyproheptadine
• Bladder emptying disorders
• Narrow-angle glaucoma
• acute asthma attack
• Pregnancy, lactation
• Children
• Babies
• Infants
• Lactation
• Concurrent 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 of the use of cyproheptadine for weight gain found significant weight gain in 39 of 46 studies evaluated. In contrast, little benefit of cyproheptadine was found in malignant/progressive diseases, such as HIV and cancer. 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 (adults 81.7%, children 18.3%) in the French pharmacovigilance database from 1985 to 2020⁵
Primarily these were

• 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 drug. Use in young children was not recommended as a precaution. Liver values should be monitored.

5. Cyproheptadine for weight gain in ADHD¶

Many ADHD sufferers 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 show good effects on ADHD symptoms.

One ADHD sufferer (36 kg) reported that in her case, 10 ml of cyproheptadine successfully resolved stimulant-induced appetite reduction.

In contrast, a study of the preventive effect of 1 to 12 mg cyproheptadine on methylphenidate-induced sleep and appetite problems in 40 children 2 to 12 years of age found no differences from the placebo group.⁶

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