How Do You Choose a Second-Line Treatment Option for Depression?




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A majority of patients with major depression do not remit or adequately respond to initial antidepressant therapy. When response is insufficient, a diagnosis of depression and any comorbidities should be confirmed, treatment adherence should be established, and antidepressant dosages should be optimized as tolerated. If response is still insufficient, then implementing second-line treatment strategies is warranted. Second-line strategies of switching to or combining/augmenting the initial agent with one of a variety of antidepressant medications and/or psychotherapies improves remission rates, although no single approach or agent has demonstrated clear superiority over any other. Second-line treatment selections should be driven by safety considerations, patients’ symptom profiles, and patient preference. Comorbid medical conditions, especially cardiac and cerebrovascular complications, and potential drug-drug interactions should be considered when making treatment decisions.

From the Department of Psychiatry, University of North Carolina, Chapel Hill; Department of Psychiatry, Duke University, Durham, North Carolina; and private practice, Raleigh, North Carolina.

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 Weisler has been/is a member of the speakers bureaus for Abbott, AstraZeneca, Biovail, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Ciba Geigy, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Novartis, Organon, Pfizer, Sanofi, Sanofi-Synthelabo, Shire, Solvay, Validus, and Wyeth; has been/is a consultant for Abbott, AstraZeneca, Biovail, Bristol-Myers Squibb, Cephalon, Corcept, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Otsuka, Pfizer, Pharmacia, ProPhase, Sanofi, Sanofi-Synthelabo, Shire, Solvay, Takeda, Validus, and Wyeth; has received/is receiving research support from Abbott, AstraZeneca, Biovail, Bristol-Myers Squibb, Burroughs Wellcome, Cenerx, Cephalon, Ciba Geigy, CoMentis, Dainippon Sumitomo, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, McNeil, Medicinova, Merck, the National Institute of Mental Health, Neurochem, New River, Novartis, Organon, Pfizer, Pharmacia, Repligen, Saegis, Sandoz, Sanofi, Sanofi-Synthelabo, Schwabe/Ingenix, Sepracor, Shire, Synaptic, Takeda, TAP, UCB, Vela, and Wyeth; and was/is a stock shareholder of Bristol-Myers Squibb, Cortex, Merck, and Pfizer.

Corresponding author: Richard H. Weisler, MD, 700 Spring Forest Rd, Ste 125, Raleigh, NC 27609 (

J Clin Psychiatry 2010;71(suppl 1):21-26