Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder

Background: The long-term efficacy and tolerability of the antidepressant reboxetine, a unique selective norepinephrine reuptake inhibitor (selective NRI), were assessed in an international study. Method: Two hundred eighty-three patients with recurrent DSM-III-R major depression who responded to 6 weeks of reboxetine treatment (greater than or equal to 50% decrease in Hamilton Rating Scale for Depression [HAM-D] total score) were randomly assigned to receive reboxetine or placebo for 46 weeks in a double-blind phase. Relapse (greater than or equal to 50% increase in HAM-D total score and/or a HAM-D total score greater than or equal to 18) rate was the principal assessment criterion and included patients who experienced relapse or recurrence. Only patients who remained relapse-free at the end of the first 6-month treatment period were included in the relapse rate assessment at the end of the second 6-month treatment period. Results: Reboxetine was associated with a markedly lower relapse rate than placebo (22% vs. 56%; p < .001) and a greater cumulative probability of a maintained response (p = .0001) during long-term treatment. Patients in remission (HAM-D total score less than or equal to 10) at the time of random assignment were less likely to relapse (16% reboxetine, 48% placebo; p < .001). The proportion of patients who were relapse-free and therefore remained in the study was significantly (p < .001) higher among those on reboxetine treatment than on placebo at the end of the first (61% vs. 40%) and second (88% vs. 59%) 6 months of treatment. Additional efficacy measures supported these findings. The incidence of adverse events with reboxetine was low and comparable with that for placebo. Discontinuation due to adverse events occurred infrequently. Conclusion: Reboxetine treatment over 1 year is more effective than placebo in the prevention of relapse in patients with recurrent depression. The low relapse rates at the end of the second 6 months of treatment further suggest that reboxetine effectively prevents recurrence of depressive symptoms following episode resolution. Reboxetine is well tolerated in long-term treatment of depression, a finding that bodes well for long-term patient compliance.