ACP Updates Clinical Guidelines for Major Depressive Disorder Treatment

The updated recommendations include both nonpharmacologic and pharmacologic interventions for adults in the acute phase of MDD.

The American College of Physicians (ACP) has issued updated guidelines for the treatment of major depressive disorder (MDD). The recommendations include both nonpharmacologic and pharmacologic interventions for adults in the acute phase of MDD based on a systematic review of available evidence.

For initial treatment of moderate to severe MDD, ACP recommends monotherapy with either cognitive behavioral therapy (CBT) or a second generation antidepressant (eg, selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs], bupropion, mirtazapine, nefazodone, trazodone, vilazodone, vortioxetine). If an antidepressant is initiated, the guidelines suggest starting treatment with a low dose to reduce the chances of side effects and improve adherence. A combination of CBT and second generation antidepressant as initial treatment was also suggested as an alternative treatment option.

For patients with moderate to severe MDD who do not respond to initial treatment with an adequate dose of a second generation antidepressant, the clinical guidelines committee (CGC) recommends switching to or adding CBT or switching to a different second generation antidepressant or adding a second pharmacological agent (eg, mirtazapine, bupropion, buspirone).

For patients with mild MDD, monotherapy with CBT is suggested for initial treatment. If access or cost of CBT is a concern, or if the patient has a history of moderate to severe MDD, a second generation antidepressant may be considered for initial treatment, according to the CGC.

When making treatment decisions, the guidelines stress the importance of informed decision making, taking into account patient preferences, the potential benefits and harms of treatment, comorbidities, concomitant medications, and cost.

Additional clinical considerations are available in the full guideline.

This article originally appeared on MPR


  1. American College of Physicians recommends cognitive behavioral therapy or second-generation antidepressants for adults with major depressive disorder. News release. January 23, 2023.
  2. Qaseem A, Owens DK, et al. Nonpharmacologic and pharmacologic treatments of adults in the acute phase of major depressive disorder: a living clinical guideline from the American College of Physicians. Published online January 24, 2023. Annals of Internal Medicine.