SAGE-547 (SAGE Therapeutics) is a new drug, an allosteric modulator of GABAA receptors, which is currently under investigation for the treatment of refractory seizure disorders.  It turns out that SAGE-547 may also be useful for the treatment of severe postpartum depression (PPD).

In a press release last month, SAGE Therapeutics announced data from an exploratory clinical trial demonstrating a statistically significant improvement in depressive symptoms in four women with postpartum depression within 24 hours of intravenous treatment with SAGE-547.

The women included in this study had severe depressive symptoms with a mean score of 26.5 on the Hamilton Depression Rating Scale (HAM-D).  All participants had an inadequate response to prior antidepressant therapy.  After treatment with intravenous SAGE-547, the mean HAM-D score declined to 1.8.  (A HAM-D score of less than 7 is considered to be depression-free.)  SAGE-547 was well-tolerated with no serious adverse events reported during treatment or during the 30-day follow-up period.  No patients discontinued treatment. The only adverse event reported in more than one patient was sedation, which was noted in two patients.

What’s Next?

Given the potential severity of this disorder and the strength of the initial signal, the company plans to move from the initial open-label trial to a larger placebo-controlled trial.

This is a very small preliminary study, but it is rather exciting.  The women included in this study are not the typical patients we see with postpartum depression; these were women with severe depressive symptoms who have failed conventional antidepressant therapy.  Previous studies with antidepressants have shown high response rates, usually around 80% or higher.  But we do see women who have more refractory and persistent depressive symptoms, and SAGE-547 may be an option for this group of women.

The other exciting thing about SAGE-547 is the rapidity of the response — remission of depression within 24 hours!  Because antidepressants typically take 2-4 weeks to kick in, an antidepressant agent with rapid onset of action would be particularly appealing to women with severe PPD, particularly women with suicidality.  (We have seen a similarly rapid response when ketamine is used to treat depression.  We do not fully understand ketamine’s mechanism of action, it also interacts with GABA-A receptors.)

More information regarding participation in this trial can be found at clinical

Ruta Nonacs, MD PhD


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