What are the side effects of Cuproheptadine?

Cyproheptadine Side Effects

Cyproheptadine causes significant sedation (9-11% incidence), anticholinergic effects including cognitive impairment particularly in elderly patients, and weight gain, with additional risks of CNS depression when combined with alcohol or other sedatives. 1

Central Nervous System Effects

Sedation and Cognitive Impairment

• Sedation is the most common side effect, occurring in 9-11% of patients, and significantly impairs driving ability and mental alertness even when patients are unaware of the impairment. 1, 2
• Cognitive decline is especially concerning in elderly patients due to anticholinergic properties, placing cyproheptadine in the category of high-risk medications that should be deprescribed in older adults with cognitive impairment. 3
• In children, cyproheptadine may paradoxically produce excitation rather than sedation, and central anticholinergic effects can predominate in pediatric overdoses. 2, 4
• Patients should be warned against engaging in activities requiring mental alertness and motor coordination, such as driving or operating machinery. 2

Psychiatric Effects

• Anticholinergic psychosis can occur, manifesting as agitation, confusion, and hallucinations, particularly in overdose situations. 4
• In PTSD patients, cyproheptadine may worsen symptoms such as nightmares and restlessness according to the American Academy of Sleep Medicine. 3

Anticholinergic Side Effects

The atropine-like action of cyproheptadine produces multiple peripheral and central anticholinergic effects. 2

Peripheral Anticholinergic Effects

• Dry mouth 1
• Dry eyes 1
• Constipation 1
• Urinary retention 1
• Risk of narrow-angle glaucoma 1

Special Precautions for Anticholinergic Effects

Cyproheptadine should be used with caution in patients with: 2

• History of bronchial asthma
• Increased intraocular pressure
• Hyperthyroidism
• Cardiovascular disease
• Hypertension

Metabolic Effects

• Weight gain occurs in approximately 10% of patients (15/151 patients in one pediatric study). 5
• The antiserotonergic activity of cyproheptadine contributes to appetite stimulation and subsequent weight gain. 3

Drug Interactions and Enhanced Toxicity

• MAO inhibitors prolong and intensify the anticholinergic effects of cyproheptadine. 2
• Additive CNS depression occurs with alcohol and other CNS depressants including hypnotics, sedatives, tranquilizers, and antianxiety agents. 2
• Concomitant use with alcohol and other CNS-active substances should be avoided as it enhances performance impairment. 1

Serious Adverse Events

Overdose and Fatality Risk

• Fatal overdoses have been reported with cyproheptadine, particularly when combined with other medications such as citalopram. 6
• Central anticholinergic syndrome can occur in overdose, with psychiatric manifestations including agitation, confusion, and hallucinations requiring high clinical suspicion for diagnosis. 4

Cardiovascular Effects

• Cardiovascular disease patients require caution due to potential effects on heart rate and blood pressure. 2

Age-Specific Considerations

Pediatric Patients

• Safety and effectiveness have not been established in children below age 2 years. 2
• Sleepiness occurred in 13% (19/151) of pediatric patients in one study. 5
• Central effects may predominate over peripheral effects in children, with paradoxical excitation possible. 2, 4

Geriatric Patients

• Elderly patients are at particularly high risk for cognitive decline and should start at the low end of the dosing range. 2
• Greater frequency of decreased hepatic, renal, or cardiac function in elderly patients increases risk of adverse effects. 2

Pregnancy and Lactation

• Pregnancy Category B: Cyproheptadine showed fetotoxicity in rats with intraperitoneal injection at four times the maximum recommended human oral dose. 2
• Should be used during pregnancy only if clearly needed, as studies in humans cannot rule out the possibility of harm. 2
• It is unknown whether cyproheptadine is excreted in human milk; a decision should be made to discontinue nursing or discontinue the drug. 2

Common Pitfalls

• Clinicians often underestimate the cognitive impairment caused by cyproheptadine, particularly in elderly patients who may not subjectively report sedation. 1, 3
• The sedating effects can be mistaken for mood improvement due to the antiserotonergic activity. 3
• Long-term use should be avoided when possible due to cumulative anticholinergic burden, especially in elderly patients. 3