Long-term management of major depressive disorder: are differences among antidepressant treatments meaningful?

Recurrent depression poses a problem for up to 80% of patients with major depressive disorder (MDD) during their lifetime. Therefore, the optimal treatment goal established by the American Psychiatric Association and the Agency for Health Care Policy and Research is remission and virtual elimination of symptoms. Patients who have a high risk of recurrence often require maintenance therapy and long-term treatment. As a result, identification of antidepressants that are effective in maintaining remission in patients over the long-term and have acceptable tolerability profiles is important. The efficacy of antidepressants in conferring full remission and long-term recovery is an important priority for clinicians. Both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been examined for use in long-term treatment of MDD. Recently, 2 long-term (6 to 12 months), double-blind, placebo-controlled studies have shown that venlafaxine is effective in preventing relapse and recurrence. While long-term, head-to-head studies comparing SNRIs with SSRIs are rare, a recent open-label study compared venlafaxine to 4 SSRIs (fluoxetine, paroxetine, sertraline, or citalopram) in outpatients with MDD. The results show that the SNRI venlafaxine is comparable to the SSRIs in terms of remission rates, and venlafaxine may bring patients to remission earlier than SSRIs. Long-term treatment at maximally tolerated doses is also associated with similar incidence of common adverse events between venlafaxine and placebo and tolerability comparable to SSRIs. Thus, there is increasing evidence that venlafaxine and SSRIs are effective and well tolerated in long-term therapy. While it is unclear from the data if continued treatment with SNRIs confers advantages over SSRIs due to an early onset of remission, further studies will provide valuable insights into the efficacy of SNRIs and SSRIs in maintenance therapy.