Long-Term, Open-Label, Safety Study of Edivoxetine as Adjunctive Treatment for Adult Patients with Major Depressive Disorder Who Were Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment in Japan

Abstract

Edivoxetine is a highly selective norepinephrine reuptake inhibitor (NRI) that has been investigated in short-term studies as adjunctive therapy to selective serotonin reuptake inhibitor antidepressants (SSRIs) in patients with major depressive disorder (MDD) who were partial responders to their SSRIs. This 52-week open-label study investigated the safety and tolerability of longer-term treatment with adjunctive edivoxetine in patients with MDD in Japan, who had completed one of two placebo-controlled acute studies of edivoxetine as adjunctive therapy to SSRIs. All patients continued on their stable dose of SSRI. Two hundred eighty-eight patients were enrolled and assessed for up to 1 year using standard safety and tolerability measures. Of these, 195 patients previously received only placebo in the parent study and, therefore, were first exposed to edivoxetine in this study. Approximately 46% of patients completed the study. The most frequently cited (>5%) reasons for discontinuation were sponsor decision (19.4%, which included patients discontinued due to early study termination), adverse event (17.4%) and subject decision (8.7%). Adverse events leading to discontinuation in more than 2 patients (>1%) were palpitations, vomiting, hepatic function abnormal, hypertension, nausea, and tachycardia. Treatment-emergent elevations in diastolic blood pressure and pulse were at least twice that reported in the literature for non-Asian patients. Twenty percent of patients had sustained elevations in pulse. Treatment-E. S. Monkul et al. 187 emergent changes in laboratory measures were small and not clinically meaningful. Assessment across all safety measures in this study indicated that the safety profile of edivoxetine was consistent with that expected for a selective NRI.