Redefining Antidepressant Efficacy Toward Long-Term Recovery

Most studies of antidepressant therapy assess short-term or acute phase efficacy and tolerability. However, 30% to 50% of patients with major depression will experience a relapse during the 4 to 6 months following treatment of a depressive episode. Patients who do not remit fully during the acute phase of therapy are at particularly high risk for relapse. In addition, 75% to 80% of patients will experience recurrent depression during their lifetime. Thus, full remission and long-term recovery, rather than short-term response, are the desired outcomes from antidepressant treatment. There is a need for prospective, long-term studies to investigate the response and recovery to antidepressant therapy. Research conducted by our group at the University of Pittsburgh has demonstrated that the rate of recurrence can be significantly reduced across 3 to 5 years of continuous treatment with imipramine. Although relatively little research on longer term, preventative pharmacotherapy has been conducted, studies with newer agents including selective serotonin reuptake inhibitors (SSRIs), nefazodone, and mirtazapine also indicate a lower relapse rate with active drug compared with placebo. The long-term efficacy of venlafaxine has been demonstrated in both an extension study and a recent prospective, double-blind discontinuation study. There is increasing evidence that antidepressants, including the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, are well tolerated and effective options for longer term therapy.