Objective: New evidence indicates that treatment response can be predicted with high sensitivity after 2 weeks of treatment. Here, we assess whether early improvement with antidepressant treatment predicts treatment outcome in patients with major depressive disorder (MDD). Data Sources: Forty-one clinical trials comparing mirtazapine with active comparators or placebo in inpatients and outpatients (all-treated population, N= 6907; intent-to-treat population, N= 6562) with MDD (DSM-III-R or DSM-IV Criteria) were examined for early improvement (≥ 20% score reduction from baseline on the 17-item Hamilton Rating Scale for Depression [HAM-D-17] within 2 weeks of treatment) and its relationship to treatment outcome. Study Selection: Data were obtained from a systematic search of single-or double-blind clinical trials (clinical trials database, Organon, a part of Schering-Plough Corporation, Oss, The Netherlands). All included trials (a total of 41) employed antidepressant treatment for more than 4 weeks and a maximum of 8 weeks. The studies ranged from March 1982 to December 2003. Trials were excluded if there were no HAM-D-17 ratings available, no diagnosis of MDD, or if the study was not blinded. Trials were also excluded if HAM-D-17 assessments were not available at week 2, week 4, and at least once beyond week 4. Data Synthesis: Early improvement predicted stable response and stable remission with high sensitivity (≥ 81% and≥ 87%, respectively). Studies utilizing rapid titration vs. slow titration of mirtazapine demonstrated improved sensitivity for stable responders (98%,[95% CI= 93% to 100%] vs. 91%[95% CI= 89% to 93%]) and stable remitters (100%,[95% CI= 92% to 100%] vs. 93%[95% CI= 91% to 95%]). Negative predictive values for stable responders and stable remitters were much higher (range= 82%–100%) than positive predictive values (range= 19%–60%).

Conclusions: These results indicate that early improvement with antidepressant medication can predict subsequent treatment outcome with high sensitivity in patients with major depressive disorder. The high negative predictive values