Postpartum depression: Novel treatment yields positive results in phase 3 trial

Postpartum depression (PPD) is one of the most common problems experienced by women during pregnancy, according to a report by WHO last year about 22 percent of Indian mothers suffer from PPD. A new investigational drug, SAGE-217, was found to significantly reduce depressive symptoms in PPD patients after just 2 weeks of treatment compared to placebo, according to results from the phase 3 trial. The drug also reduced depression-remission rates and anxiety.

Results were presented at the 32nd European College of Neuropsychopharmacology (ECNP) Congress.

The phase 3 trial that Vieta reported on included more than 150 women aged 18 to 45 years who were no more than 6 months postpartum, had been diagnosed with PPD, and had a score of at least 26 on the Hamilton Depression Rating Scale (HAM-D).

The women were randomly assigned in a double-blind 1:1 fashion to SAGE-217 30 mg or placebo once daily for 14 days, followed by naturalistic follow-up out to 45 days.

Key findings of the study include:

• By day 3, the SAGE-217 group had achieved a significantly greater reduction in HAM-D scores over baseline than the placebo group (mean reduction, 12.5 vs 9.8, respectively).


• The difference in mean scores steadily increased up to day 15, the primary endpoint, when the mean reduction in HAM-D scores over baseline was 17.8 vs 13.6, respectively.


• By day 45, women treated with SAGE-217 had experienced an average reduction in HAM-D scores over baseline of 19.2 vs 15.1 for those treated with placebo.


• The active treatment group also experienced significantly greater reductions over baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) scores vs placebo (day 15 average reductions, 22.1 vs 17.6, respectively).


• By day 45, the mean reductions in MADRS scores had increased to 24.8 for the SAGE-217 group and 19.0 for those given placebo.


• At days 8, 15, and 45, significantly more women given the active drug had a HAM-D response, defined as a 50% or greater reduction in total score.


• The drug significantly more achieved HAM-D remission, defined as a total score of 7 or greater, at days 3, 15, and 45.


• Treatment with SAGE-217 was also associated with a significant reduction in Hamilton Anxiety Rating Scale scores over baseline compared with placebo, at a mean reduction of 16.6 vs 12.7


• Vieta said that the proportion of patients with treatment-emergent adverse events (AEs) was similar in the SAGE-217 and placebo groups (60.3% vs 52.1%, respectively).


• The most common AEs for the active treatment were somnolence (15.4%), headache (9%), dizziness (7.7%), upper respiratory tract infection (7.7%), and diarrhoea (6.4%).


• There was no indication of an increase in suicidal ideation or suicidal behaviour over baseline, as measured with the Columbia Suicide Severity Rating Scale (C-SSRS).

About SAGE-217

SAGE-217 is an investigational medication which is under development by SAGE. It is a neurosteroid with oral bioavailability. It acts as a positive allosteric modulator of synaptic and, unlike benzodiazepines, extrasynaptic gamma-aminobutyric acid (GABA) A receptors.