Zuranolone is a recently approved oral therapy for postpartum depression. Its mechanism of action is best described as:

• A Selective serotonin reuptake inhibition with 5-HT1A partial agonism
• B Irreversible monoamine oxidase inhibition with dopaminergic releasing activity
• C Competitive antagonism at NMDA receptors with mu-opioid agonism
• D Positive allosteric modulation of synaptic and extrasynaptic GABA-A receptors ✓

Explanation

Zuranolone is a synthetic analogue of allopregnanolone, a neuroactive steroid metabolite of progesterone whose levels fall abruptly after delivery. It acts as a positive allosteric modulator at both synaptic and extrasynaptic GABA-A receptors and is given once nightly for 14 days, producing response within days. SSRIs act over weeks, and ketamine-class NMDA antagonism is a separate mechanism used in resistant depression.

Reference: Stahl's Essential Psychopharmacology, 5th ed.

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Written and medically reviewed by the StethoPrep medical team.