When should you move beyond first-line therapy for depression?

The probability of achieving and sustaining symptomatic remission in major depressive disorder (MDD) with first-line pharmacotherapy is approximately 30%. Ample documentation shows that the maximal therapeutic effect obtained with antidepressant pharmacotherapy is approximately 4 to 6 weeks, perhaps longer for individuals receiving manual-based psychotherapies. Emerging evidence also indicates that early (ie, at 2 weeks) symptomatic improvement (ie, ≥ 20% improvement on the 17-item Hamilton Depression Rating Scale score) positively predicts remission at weeks 6 to 8 (nonimprovement at week 2 may be a more robust negative predictor of nonremission at weeks 6 to 8). Notwithstanding the identification of early positive/negative remission prediction, a subgroup of individuals receiving pharmacotherapy evinces initial improvement beyond week 6 of treatment. Available evidence does not support a claim that any antidepressant or class of antidepressants offers a faster onset of action. Identifying moderators and/or predictors of response is a priority research vista; hitherto, no biomarker has emerged as a reliable predictor of treatment efficacy, tolerability, or safety. Emerging evidence suggests that electrophysiological measures, ie, frontal quantitative electro encephalography (QEEG) may be capable of identifying antidepressant remitters within 1 to 2 weeks of exposure. Taken together, practitioners are often faced with the critical question as to when to move beyond index therapy for treating depressive symptoms as part of MDD.