FDA-Approved Indications for Periactin (Cyproheptadine) in Psychiatry
Cyproheptadine has NO FDA-approved psychiatric indications. The FDA has approved cyproheptadine solely as a first-generation H1-antihistamine for treating allergic-type symptoms and rhinorrhea in adults and pediatric patients aged 2 years and older 1.
Primary FDA-Approved Use
- Cyproheptadine is approved exclusively for allergic conditions, with standard adult dosing of 4 mg three times daily and pediatric formulations available as 2 mg/5 mL syrup 1.
- The medication provides superior control of rhinorrhea compared to second-generation antihistamines due to its anticholinergic properties 1.
Critical Non-Psychiatric Emergency Use (Off-Label)
While not a psychiatric indication, cyproheptadine serves as the preferred antidote for severe serotonin syndrome, a life-threatening condition that can occur with psychiatric medications 2, 1:
- The American Academy of Pediatrics specifically recommends cyproheptadine over other agents for severe serotonin syndrome 2, 1.
- Adult dosing begins with 12 mg orally, followed by 2 mg every 2 hours for continuing symptoms, with maintenance dosing of 8 mg every 6 hours 2, 1.
- Pediatric dosing is 0.25 mg/kg per day 2, 1.
- This condition carries an 11% mortality rate and requires ICU-level monitoring 1.
Off-Label Psychiatric Uses (Not FDA-Approved)
The following psychiatric applications lack FDA approval but have limited evidence:
- Combat-related nightmares in PTSD: The American Academy of Sleep Medicine addresses dosing ranges from 2-24 mg nightly, with median effective doses of 16-24 mg in veterans, though evidence is conflicting 1.
- Autistic disorder: One small double-blind trial showed improvement in ABC-C scores when combined with haloperidol, but this requires confirmation in larger studies 3.
- HIV-associated neuropsychiatric complications: Theoretical benefits exist for efavirenz-related side effects, but evidence remains limited and requires well-designed studies 4.
Important Safety Considerations for Psychiatric Contexts
- Cyproheptadine causes significant sedation (9-11% incidence), impairs driving ability, and can lead to cognitive decline, particularly in elderly patients 1.
- The medication has anticholinergic effects including dry mouth, constipation, urinary retention, and risk of narrow-angle glaucoma 1.
- The American Academy of Sleep Medicine reports that cyproheptadine may worsen symptoms such as nightmares and restlessness in some PTSD patients 5.
- Concomitant use with alcohol and other CNS-active substances should be avoided due to enhanced performance impairment 1.