American College of Physicians Recommends Cognitive Behavioral Therapy or Second-Generation Antidepressants for Adults With Major Depressive Disorder

Doctors and patients should discuss treatment benefits, harms, adverse effects, costs, accessibility, and patient preferences when selecting first- and second-line treatments

PHILADELPHIA, January 24 -- The American College of Physicians (ACP) has issued an update of its guideline with clinical recommendations for nonpharmacologic and pharmacologic treatments of adults in the acute phase of major depressive disorder (MDD). In the updated clinical guideline, ACP recommends the use of either cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs) as initial treatment in adults with moderate to severe MDD, and suggests the combination of both, as an alternate initial treatment option. The guideline and supporting evidence reviews are published today in Annals of Internal Medicine.

MDD is defined as the presence of a depressed mood or a loss of interest or pleasure in normally enjoyable activities, occurring along with at least four additional diagnostic criteria or symptoms for at least two weeks, and that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

"Major depressive disorder is a leading cause of disability, resulting in significant costs to individuals, society, and health care systems and is often underrecognized and undertreated," said Ryan D. Mire, MD, MACP, President, ACP. "It is critically important for patients to have continuity when being treated and managed to ensure adherence and address adverse effects. Also critical is the need for shared decision making around the best course of treatment based on preferences and including considerations around cost and access to care.”

The guideline presents updated clinical recommendations on nonpharmacologic and pharmacologic interventions as initial and second-line treatments during the acute phase of a moderate to severe MDD episode. This is based on the best available evidence of the comparative benefits and harms and consideration of patient values, preferences, and costs. Additionally it would include other considerations such as benefits, harms, feasibility, patient specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), co-morbidities, and other medication use.

ACP also suggests initiating CBT in adults with mild major depression. ACP stresses the importance of informed decision making when selecting treatment and taking patient preferences into account. In summary, ACP recommends:

  • Monotherapy with either CBT or an SGA as initial treatment in patients in the acute phase of moderate to severe MDD (strong recommendation, moderate-certainty evidence).
  • Combination therapy with CBT and an SGA as initial treatment in patients in the acute phase of moderate to severe MDD (conditional recommendation; low certainty-evidence).
  • Monotherapy with CBT as initial treatment in patients in the acute phase of mild MDD (conditional recommendation; low-certainty evidence).
  • One of the following options for patients in the acute phase of moderate to severe MDD who did not respond to initial treatment with an adequate dose of an SGA:
    • switching to or augmenting with CBT (conditional recommendation; low-certainty evidence)
    • switching to a different SGA or augmenting with a second pharmacological treatment (see Clinical Considerations) (conditional recommendation; low-certainty evidence).

The guideline is based on an accompanying comparative effectiveness living systematic review and network meta-analysis, and on two additional rapid reviews on values and preferences and cost-effectiveness analyses completed by the ACP Center for Evidence Reviews at Cochrane Austria/University for Continuing Education Krems (Danube University Krems). ACP’s Clinical Guidelines Committee is planning to maintain this topic as a living guideline with literature surveillance and periodic updating of the systematic review and the clinical recommendations.


About the American College of Physicians
The American College of Physicians is the largest medical specialty organization in the United States with members in more than 145 countries worldwide. ACP membership includes 160,000 internal medicine physicians, related subspecialists, and medical students. Internal medicine physicians are specialists who apply scientific knowledge and clinical expertise to the diagnosis, treatment, and compassionate care of adults across the spectrum from health to complex illness. Follow ACP on Twitter, Facebook, and Instagram.

Contact: Andrew Hachadorian, (215) 351-2514,