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When Should You Move Beyond First-Line Therapy for Depression?

Roger S. McIntyre, MD, FRCPC

Published: October 15, 2010

Article Abstract

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 (non improvement at week 2 may be a more robust negative predictor of non remission 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 electroencephalography (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.

From the Department of Psychiatry, University of Toronto, and the Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.

This article is derived from the planning teleconference series "Looking Past First-Line Therapy for Major Depressive Disorder," which was held in January 2010 and supported by an educational grant from AstraZeneca.

Dr McIntyre is a member of the advisory boards for AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, Shire, Schering-Plough, and Merck; is a member of the speakers bureaus for Janssen-Ortho, AstraZeneca, Eli Lilly, Lundbeck, Biovail, and Merck; has provided CME activities for AstraZeneca, Bristol-Myers Squibb, France Foundation, i3 CME, Solvay/Wyeth, CME Outfitters, Optum Health, Schering-Plough, Merck, and Eli Lilly; has received research grants from Stanley Medical Research Institute, NARSAD, Eli Lilly, Janssen-Ortho, Shire, AstraZeneca, and Pfizer; and has received travel funds from Bristol-Myers Squibb.

Corresponding author: Roger S. McIntyre, MD, FRCPC, 399 Bathurst St, MP 9-325, Toronto, ON M5T 2S8, Canada (

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