Newly released guidelines by the American College of Physicians (ACP) recommend that clinicians choose between either cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs) when treating patients with major depressive disorder (MDD).

The report, published ahead of print in the Annals of Internal Medicine, bases this strong recommendation on moderate-quality evidence, gathered via a systematic evidence review of relevant studies published between January 1990 and September 2015. Study populations included adult outpatients with MDD undergoing either an initial or second course of treatment.

The review evaluated the following classes of interventions: depression-focused psychotherapy, complementary and alternative medicine (CAM), exercise, and SGAs, according to Amir Qaseem, MD, PhD, MHA, of the ACP.

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In most studies analyzed, low-quality evidence showed “no difference in either effectiveness or adverse effects between first-line intervention using pharmacologic or nonpharmacologic treatments,” Dr. Qaseem and colleagues noted. “Moderate quality evidence showed no difference in response or discontinuation of treatment when comparing SGAs with CBT.”

ACP guidelines from 2008 note that patients typically do not achieve remission after initial treatment with SGAs. In such cases, switching therapies or augmenting treatment with additional interventions may be effective.

Additional moderate-quality evidence shows that CBT or SGAs are similarly effective for patients with MDD. Although patients may be initially prescribed SGA treatment, CBT is considered a reasonable approach and “should be strongly considered as an alternative treatment to SGAs where available,” stated Dr. Qaseem.

“Harms associated with SGAs are probably underrepresented in the included trials,” he concluded. “Thus, we conclude that CBT has no more – and probably fewer – adverse effects than SGAs.”


  1. Qaseem A, Barry MJ, Kansagara D. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016; doi: 10.7326/M15-2570