Cyproheptadine for Appetite: What the Trials Found, and How Sleepy It Makes You

Cyproheptadine does raise appetite and body weight in most underweight groups it has been tested in. It also makes most people sleepy, at least at first.

It is a prescription drug. Nothing here is a reason to take it without a doctor. This page reports what the trials found.

What is cyproheptadine?

It is a first-generation H1 antihistamine that has been on the market since the 1960s. It also blocks serotonin. Its effect on appetite was noticed early, but it is still not authorized for that use in every country. (Bertrand 2021)

Cyproheptadine uses

• Allergy. That is what an antihistamine is for.
• Appetite and weight gain in underweight children and adults. This is the use with the most trials, and the subject of this page.
• Serotonin syndrome, in hospital. In a review of 23 adult patients who met the criteria for serotonin syndrome, all were given cyproheptadine and every one showed at least some response within 24 hours. (Prakash 2024)

Cyproheptadine for appetite: what the trials found

• The systematic review. 46 articles across 21 patient groups, 32 of them randomized trials. In 39 of the 46, cyproheptadine produced significant weight gain. (Harrison 2019)
• Adults with poor appetite. 375 adults aged 19 to 64 took cyproheptadine or a placebo for 8 weeks. Appetite improved more on the drug, by a small but significant margin, and weight and BMI went up. (Kim 2021)
• Cystic fibrosis. In a 12-week trial of 18 children and adults, the drug group gained 3.45 kg against 1.1 kg on placebo. (Homnick 2004) A second trial in 25 patients aged 5 to 18 used 4 mg three times a day for 12 weeks. They gained 1.61 kg against 0.67 kg. (Epifanio 2012)
• Underweight children. 21 otherwise healthy children were randomized for 4 months. Weight gain, height gain and IGF-I were all greater on cyproheptadine. (Mahachoklertwattana 2009)
• Young children with feeding problems. In a feeding program, 82 children took it regularly. 96% of their parents reported better mealtime behavior. (Sant'Anna 2014)

How long does it take for cyproheptadine to increase appetite?

Nobody measured the first days. I looked for an abstract that reports appetite after one dose or one week and did not find one. What the trials give are the points where they checked:

• 4 weeks. 77 undernourished children aged 24 to 64 months took it for four weeks and were followed to week eight. BMI ended significantly higher than in the control group. Mean weight gain by week eight was 0.60 kg against 0.11 kg, though the difference in weight change itself was not significant. (Najib 2014)
• 8 weeks. The adult trial found better appetite scores and more weight at this point.
• 12 weeks. Both cystic fibrosis trials measured their weight gain here.
• 3 to 9 months. When the first cystic fibrosis trial was extended, patients who switched from placebo gained significantly over 3 to 6 months. Those already on the drug mostly kept the weight for the 9 months. (Homnick 2005)

So the honest answer is weeks, not hours. The shortest trial treated for 4 weeks and found a higher BMI. Anything faster than that is user reports, not data.

Does cyproheptadine make you sleepy?

Yes. It is the most consistent finding in the whole literature.

• The systematic review lists transient mild to moderate sedation as the most commonly reported side effect.
• In the 375-person adult trial the most common adverse event was somnolence.
• A French safety review found drowsiness to be the most frequent adverse effect in the published literature, in adults and children.
• In seven healthy men, a 5 mg infusion at night increased slow wave sleep and reduced REM sleep. (Chihara 1976)

The reviews call the sedation mild to moderate and transient.

Cyproheptadine side effects: the honest part

• Liver. The French pharmacovigilance database holds 93 adverse effect reports since 1985. 38 were neurological and 15 were liver complications. The authors estimate liver problems at 0.27 to 1.4 per 1,000 and note very rare cases of liver failure.
• Syrups bought online. A 40-year-old woman developed drug-induced autoimmune hepatitis 6 weeks after starting Apetamin, a cyproheptadine syrup she found on social media for weight gain. (Garland 2020)
• Growth hormone. In the sleep study above, the infusion completely blocked the night-time growth hormone release in three of seven men and reduced or delayed it in the other four. It also suppressed the early morning cortisol rise.
• It failed in cancer. 295 patients with advanced cancer took 8 mg three times a day or a placebo. Appetite was mildly better, but they lost 4.5 pounds a month against 4.9 on placebo, which is no real difference. They also had more dizziness. (Kardinal 1990)
• Eating disorders are mixed. In 72 patients with anorexia nervosa it helped the non-bulimic group and made treatment less efficient in the bulimic group. (Halmi 1986)
• Weak measurement. The systematic review notes that few studies measured appetite objectively. Most measured weight.

Cyproheptadine is a prescription medicine. Dose, timing and whether it fits you are decisions for a doctor, especially for a child.

What I do

I am not underweight and I do not use it for appetite. I take 0.5 to 1 mg at night, about an hour before bed, as part of my sleep routine with gelatin and magnesium. That is far below the trial doses above, and it is my own use, not advice.

My reason is that I see histamine and serotonin as stress signals, and histamine as the thing that keeps you awake. That is my view. The background is in how to lower serotonin and Ray Peat on histamine.

Quick answers

Does cyproheptadine work for appetite?

In a systematic review, 39 of 46 studies found significant weight gain in underweight groups. In a trial of 375 adults with poor appetite, appetite scores, weight and BMI improved more than on placebo. It showed little or no benefit in advanced cancer and HIV.

How long does it take for cyproheptadine to increase appetite?

No published abstract measures the first days. The shortest trial treated children for 4 weeks and found a higher BMI, and others measured gains at 8 and 12 weeks.

What are the side effects of cyproheptadine?

Drowsiness is the most common. A French safety review also recorded liver complications, estimated at 0.27 to 1.4 per 1,000, with very rare liver failure. One sleep study found it suppressed night-time growth hormone release.

What is cyproheptadine used for?

It is a prescription first-generation antihistamine that also blocks serotonin. It is used for allergy, is prescribed in some countries to stimulate appetite, and is given in hospital for serotonin syndrome.

Does cyproheptadine make you sleepy?

Yes. Sedation or somnolence was the most common side effect in the systematic review, the largest adult trial and the French safety review. The reviews describe it as mild to moderate and transient.