Gepirone

EXXUA

Open Gepirone in the interactive console ↗

What it isSelective 5-HT1A partial agonist with hERG blockade; major depression.

Why this oneIt produces antidepressant effects without serotonin-reuptake blockade, keeping sexual and weight effects relatively small.

What limits itModest efficacy, QT prolongation, and CYP3A4 interactions constrain use; the antidepressant suicidality warning applies.

FDA-approved for

depression (2023)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients; not approved in pediatrics.

FDA dosing	Population	Start	Target	Max
Major depressive disorder	Adults	18.2 mg QD	titrate to response	72.6 mg QD
Major depressive disorder	Geriatric	18.2 mg QD		36.3 mg QD

Titration Increase no sooner than Day 4, again after Day 7, then after 1 additional week

Renal CrCl <50 mL/min: start 18.2 mg QD; max 36.3 mg QD

Hepatic Moderate (Child-Pugh B): max 36.3 mg QD; severe: contraindicated

Instructions

Take orally with food at approximately the same time each day
Correct electrolytes and perform ECG before starting; do not initiate if QTc >450 msec
Reduce dose by 50% with a moderate CYP3A4 inhibitor

Contraindications

QTc interval >450 msec at baseline
Congenital long QT syndrome
Concomitant strong CYP3A4 inhibitors
Severe hepatic impairment
MAOIs (concurrently or within 14 days) due to risk of serotonin syndrome

Cautions

QT interval prolongation
Serotonin syndrome with other serotonergic agents
Activation of mania/hypomania
Suicidal thoughts and behaviors in young patients

Adverse reactions

Dizziness
Nausea
Insomnia
Abdominal pain
Dyspepsia

Pregnancy Insufficient human data; third-trimester exposure may cause PPHN and poor neonatal adaptation. Antidepressant pregnancy registry available.

Lactation Present in rat milk; no human data. Monitor infant for irritability, restlessness, somnolence, poor feeding, weight loss.

⚠ BOXED WARNING

Suicidal thoughts and behaviors in patients under 25

Principal riskModest efficacy and QT prolongation

Cost, est. cash$700–$1,100/month

Generic entry2037 est.

Classes and tags

Clinical profile

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability1 / 4

Sedation liability1 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryNot assigned — PLLR-era drug

Defining liabilitySexual/GI effects, hyponatremia, discontinuation and serotonin toxicity; overdose danger varies substantially by agent.

Active metabolites

1-PP

Mechanism of action: Gepirone ballicule

Gepirone ballicule: receptor binding, kinetics and half-life diagram

Open Gepirone in the interactive console ↗

Memory aids: mascots and interaction avatars

Gepirone EXXUA mascot mnemonic cartoon — **“(-Ex, you a) Jeeper”**
”#1 pee pee” → 1-pp metabolite
”not a bus” – buspirone (Buspar) is the other medication classified as a 5-HT1A partial agonist
the spear on the jeep conveys similarity to Buspar mascot, which has a “bus”spear

Open Gepirone in the interactive console ↗