Zuranolone ($ Zurzuvae)

Neurosteroid (allopregnanolone analogue) with GABA properties

Dosing

50 mg qhs for 2 weeks, take with a high-fat meal to aid absorption

Management

Zuranolone works rapidly for postpartum depression but is only given as a two-week course. It is a synthetic version of the neurohormone allopregnanolone, whose levels rise during pregnancy, fall postpartum (and rise again with cessation of breastfeeding and return of menses).

Can give a second course if relapse within a year of childbirth, but don’t recommend a third course.

Zuranolone is safe in bipolar, and may help bipolar depression (25-50% of postpartum depressions are bipolar).

Zuranolone is given postpartum but not during pregnancy. It was tested in women whose depression began sometimes between the third trimester and up to 4 weeks after delivery (the DSM definition; ICD goes to 6 weeks). Caution if starting zuranolone for depressions that begin after stopping breastfeeding and resuming menses (these depressions are linked to a rise in allopregnanolone).

Do not use for regular depression (FDA declined it due to failed trials. It has benzo-like properties, and alprazolam has good evidence to speed antidepressant response from 21 controlled trials (van Marwijk H et al, Cochrane Database Syst Rev 2012;2012(7)) where it treated anxiety and core symptoms of depression. So that is a better option for MDD than zuranolone, but clearly not a good option, and the benzo similarity reminds us not to use zuranolone for more than two weeks.

TOLERABILITY: Sedation, diarrhea.

RISKS: Driving impairment, risk of misuse. Do not use while breastfeeding (but can pump and discard milk during treatment so they don’t lose ability to breastfeed). With long-term use: tolerance, withdrawal, misuse.

EMR Text