New Depression drug with novel mechanism of action gives instant results
Researchers in a phase 2 trial, assessed the efficacy and safety of a new antidepressant drug SAGE-217 with a novel mechanism of action. The effects of currently used antidepressants are variable and generally emerge within 4 to 8 weeks. The trial showed that the administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15.
SAGE-217, the non-FDA approved drug, is an oral positive allosteric modulator of GABAA receptors similar to brexanolone -- a rapidly acting intravenous agent for postpartum depression.
In this double-blind, phase 2 trial, the researchers enrolled 89 patients with major depression. They were randomly assigned in the ratio 1:1 to receive 30 mg of SAGE-217 (n=45) or placebo (n=44) once daily. The outcomes were assessed for 2 more weeks.
The primary endpoint was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy endpoints, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse).
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Key findings include:
- The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group.
- The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was −17.4±1.3 points in the SAGE-217 group and −10.3±1.3 points in the placebo group.
- The differences in secondary endpoints were generally in the same direction as those of the primary endpoint.
- There were no serious adverse events.
- The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence.
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"Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments," concluded the authors.
To read the complete study log on to DOI: 10.1056/NEJMoa1815981