This 12-month open-label, but dose-blinded extension phase,
evaluated the safety and tolerability of flexibly-dosed edivoxetine (6, 9, 12 or 18 mg once
daily) in patients (N = 397)
with major depressive disorder, who completed the 10-week randomized,
double-blind, placebo-controlled acute phase of the study.All patients were
treated with edivoxetine during the extension phase. The mean age of the patients was 45
years, and most were white females.
Safety evaluations included assessment of treatment-emergent adverse events
(TEAEs), laboratory and vital sign measures, and suicidality. Within-group
t-tests based on a 2-sided significance level of 0.05 and 95% confidence levels
were used to assess whether changes from baseline were statistically
significant from zero. The overall completion rate was 54%. Adverse event was
the most common (14.4%) reason for discontinuation, which included blood
pressure increased (1.3%), heart rate increased (1.3%), anxiety (1.0%), and
tachycardia (1.0%). At least 1 TEAE was reported by 72.3% of patients, of which
headache (10.8%) and hyperhidrosis (10.1%) were the most common; 2.8% of
patients had ≥1 serious adverse events, and there were no completed suicides. No clinically relevant changes were
observed in most laboratory measures. Potentially clinically significant
changes in ALT values occurred in 1.8% of patients, and either normalized or
had decreased by the last
assessment. Mean increases in blood pressure and pulse were consistent with
those observed in the acute phase and appeared to reach a plateau within 3 to 5
months of treatment. In conclusion, safety and tolerability findings during
this long-term extension phase evaluation of edivoxetine were consistent with
its norepinephrine reuptake inhibition profile.