Cyproheptadine for ADHD

The treatment of ADHD with stimulants sometimes shows the side effect of appetite inhibition.
In this section we collect medicines that can counteract this.

An animal study indicates a weight-promoting aspect of augmentative administration of fluoxetine. However, due to the considerable side effects of antidepressants, this is unlikely to be useful in practice.¹

• 1. Mechanisms of action of cyproheptadine
• 2. Indications for use of 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 a²

• 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 cyproheptadine³²

• 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 cyproheptadine³²

• 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.⁴
A recent larger RCT also found cyproheptadine to be an effective and safe medication for weight gain in adults.⁵

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%)⁶
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, use in small children was not recommended. 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 stimulants⁷
A person with ADHD (36 kg) reported that 10 ml of cyproheptadine successfully corrected her appetite reduction caused by stimulants.

Pliszka reports an appetite-enhancing and sleep-promoting effect in ADHD⁸⁹

In contrast, 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.¹⁰

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.