Number Needed to Treat and Number Needed to Harm analysis of the zuranolone phase 2 clinical trial results in major depressive disorder.

ABSTRACT

BACKGROUND: Zuranolone (SAGE-217) is a novel, investigational positive allosteric modulator of GABAA receptors being investigated in major depressive disorder (MDD). This analysis of phase 2 data quantified the benefit and risk of zuranolone (30mg) versus placebo and antidepressants in terms of number needed to treat (NNT) and number needed to harm (NNH). METHODS: Rates of response, remission, and all-cause discontinuation for zuranolone and 11 antidepressant comparators were obtained from the zuranolone phase 2 clinical study (N=89) and a published network meta-analysis, respectively. An indirect treatment comparison was conducted using the Bucher method to compare zuranolone to standard-of-care. RESULTS: Zuranolone demonstrated greater benefit compared to placebo on Day 3 (NNT range for response=4-5, NNT for remission=10) and at Day 15 (NNT=3 for response and remission). Compared to SSRIs and SNRIs, zuranolone at Day 15 showed improved treatment response (NNT=4 [95% CI = 3; 16] and 5 [95% CI = 3; 25], respectively) and remission (NNT=4 [95% CI = 2; 13] and 4 [95% CI = 2; 18], respectively). This was accompanied by a reduction in all-cause discontinuation, with negative NNH values (-57 and -28), respectively. LIMITATIONS: Variations in study design across the included trials may limit the generalizability of results. CONCLUSIONS: With a small positive NNT as early as Day 3 indicating robust benefit and a negative NNH indicating reduced harm, this analysis based on a phase 2 study suggests that patients with MDD may benefit from the benefit-to-risk profile of zuranolone.