From the Guidelines
Cyproheptadine is recommended for the management of serotonin syndrome at doses of 8-32 mg daily, with a typical starting dose of 12 mg, followed by 2 mg every 2 hours for continuing symptoms, and a maintenance dose of 8 mg every 6 hours, given orally, as it has been shown to be effective in treating this condition 1.
Key Points
- Cyproheptadine is an antihistamine medication that blocks histamine H1 receptors and has anticholinergic and antiserotonergic activities.
- It is used to treat allergic reactions, stimulate appetite in underweight patients, prevent migraine headaches, and manage serotonin syndrome.
- The medication is available as a 4 mg tablet, typically dosed at 4-20 mg daily divided into multiple doses.
- For adults, treatment usually starts with 4 mg three times daily, while children receive weight-based dosing (0.25 mg/kg/day).
- Common side effects include drowsiness, dry mouth, and increased appetite.
- Cyproheptadine should be used cautiously in elderly patients, those with glaucoma, urinary retention, or cardiovascular disease, and patients should avoid alcohol while taking the medication.
Dosage and Administration
- The pediatric dosage is usually 0.25 mg/kg per day.
- There is no parenteral form, but tablets have been crushed and administered via a nasogastric tube.
- For the management of serotonin syndrome, the dose is typically 12 to 24 mg over 24 hours, starting with 12 mg, followed by 2 mg every 2 hours for continuing symptoms, and a maintenance dose of 8 mg every 6 hours, given orally.
Important Considerations
- Cyproheptadine has been shown to be effective in treating serotonin syndrome, a condition characterized by excessive serotonin levels, which can lead to severe symptoms such as agitation, hyperthermia, and autonomic instability 1.
- The medication works by antagonizing histamine, serotonin, and acetylcholine receptors, which explains its diverse effects.
- Patients should be monitored for side effects, and the medication should be used cautiously in certain patient populations, such as the elderly and those with certain medical conditions.
- Additionally, cyproheptadine may be used in the treatment of mast cell activation syndrome (MCAS), as it has antihistamine and antiserotonergic properties, which can help alleviate symptoms of this condition 1.
From the FDA Drug Label
CLINICAL PHARMACOLOGY Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects. Pharmacokinetics and Metabolism After a single 4 mg oral dose of 14C-labelled cyproheptadine hydrochloride in normal subjects, given as tablets, 2% to 20% of the radioactivity was excreted in the stools. Only about 34% of the stool radioactivity was unchanged drug, corresponding to less than 5. 7% of the dose. At least 40% of the administered radioactivity was excreted in the urine. No detectable amounts of unchanged drug were present in the urine of patients on chronic 12 mg to 20 mg daily doses. The principle metabolite found in human urine has been identified as a quaternary ammonium glucuronide conjugate of cyproheptadine. Elimination is diminished in renal insufficiency.
The main mechanism of action of Cyproheptadine is as a serotonin and histamine antagonist with anticholinergic and sedative effects 2.
- Pharmacokinetics: After oral administration, the drug is excreted in the stools and urine, with the principle metabolite being a quaternary ammonium glucuronide conjugate.
- Elimination: The drug's elimination is diminished in renal insufficiency. The dosage form available is a 4 mg tablet for oral administration 2.
From the Research
Overview of Cyproheptadine
- Cyproheptadine is an appetite stimulant that has been used to promote weight gain in various populations, including those with cystic fibrosis, cancer, and HIV 3, 4, 5, 6, 7.
- The medication has been shown to be effective in increasing weight and appetite in both children and adults, with minimal side effects 4, 5, 6, 7.
Efficacy in Cystic Fibrosis
- A study published in 2022 found that cyproheptadine may produce a larger increase in weight and weight z score in patients with cystic fibrosis compared to placebo 3.
- Another study published in 2005 found that cyproheptadine was effective in promoting weight gain in patients with cystic fibrosis over a longer term, with minimal side effects 6.
Efficacy in Other Populations
- A study published in 2021 found that cyproheptadine was effective in increasing appetite and weight in adults with poor appetite, with minimal side effects 4.
- A study published in 2008 found that cyproheptadine was effective in promoting weight gain in children with cancer-related cachexia, with minimal side effects 5.
- A systematic review published in 2019 found that cyproheptadine was effective in promoting weight gain in various populations, including those with malignant or progressive disease states, although the evidence was heterogeneous and few studies provided objective measures of appetite change 7.