Gepirone (Exxua)

Class

Selective 5-HT1A receptor partial agonist

Mechanism

Partial agonist at serotonin 5-HT1A receptors, modulating serotonergic neurotransmission with minimal activity at other receptors.

FDA-Approved Use

Major depressive disorder (MDD)

Off-Label Use

Various anxiety disorders, hypoactive sexual desire disorder (HSDD)

Formulation

Oral extended-release tablets (18.2 mg)

Titration

18.2 mg p.o. daily; increase to 36.3 mg/day on day 4, 54.5 mg/day on day 7, up to 72.6 mg/day by day 14 based on response and tolerability

Dose Range

18.2–72.6 mg/day

Kinetics

Half-life approximately 12 hours; metabolized primarily via CYP3A4

Common AEs

Dizziness, nausea, headache, somnolence

Serious/Rare AEs

Serotonin syndrome (when combined with other serotonergic agents)

Monitoring

Monitor for serotonergic effects and tolerability, especially when combined with other serotonergic drugs

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD

Considerations

Gepirone lacks the sedating, anticholinergic, and sexual side effects commonly seen with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). It is not associated with withdrawal symptoms or abuse potential, making it potentially preferable in patients sensitive to serotonergic or activating agents.