GH001 Efficacy is Independent of Prior Antidepressant Treatment Failures in Treatment-Resistant Depression: A Post Hoc Analysis of a Phase 2b Randomized Controlled Trial.

Abstract

<h4>Background</h4>Approximately 30% of patients treated for major depressive disorder develop treatment-resistant depression (TRD). The STAR*D study demonstrated remission rates decline progressively with each antidepressant failure (37%, 31%, 14%, and 13%, respectively). A single-day individualized dosing regimen of GH001 (synthetic mebufotenin for inhalation) produced rapid, large improvements in depressive symptoms versus placebo in patients with TRD in a Phase 2b trial (least-squares mean difference, -15.5; effect size, -2.0; 57.5% remission at Day 8 versus 0% placebo). The current post hoc analysis examines whether GH001 efficacy varies by number of prior lifetime antidepressant treatment failures.<h4>Methods</h4>This analysis included all 40 patients who received GH001 in the double-blind part of a Phase 2b trial. Spearman rank correlations between number of prior lifetime antidepressant failures and change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) scores were calculated at Day 8 and among 6-month open-label extension completers. Remission rates (MADRS ⩽10) were examined by subgroup (2, 3, 4, or ⩾5 prior lifetime failures).<h4>Results</h4>No meaningful correlation was observed between prior lifetime treatment failures and MADRS improvement at Day 8 (r = -0.13; P = 0.44) or 6-month OLE completers (r = -0.10; P = 0.60). Remission rates at Day 8 likewise were similar across subgroups (range, 53.9%-63.6%) and were maintained at end of treatment visit/Month 6 (range, 61.5%-85.7%). Secondary endpoints were not associated with treatment history.<h4>Conclusions</h4>The efficacy of GH001 in patients with TRD appears largely independent of number of prior lifetime antidepressant treatments, and further research in patients with extensive treatment histories will be conducted in subsequent development stages.

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