Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians

The purpose of this guideline from the American College of Physicians (ACP) is to present updated clinical recommendations on nonpharmacologic and pharmacologic interventions as initial and second-line treatments during the acute phase of a major depressive disorder (MDD) episode, based on the best available evidence on the comparative benefits and harms, consideration of patient values and preferences, and cost.The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of the evidence.The audience for this guideline includes clinicians caring for adult patients in the acute phase of MDD in ambulatory care. The patient population includes adults in the acute phase of MDD.ACP recommends monotherapy with either cognitive behavioral therapy or a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (strong recommendation; moderate-certainty evidence).ACP suggests combination therapy with cognitive behavioral therapy and a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (conditional recommendation; low-certainty evidence).The informed decision on the options of monotherapy with cognitive behavioral therapy versus second-generation antidepressants or combination therapy should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences.ACP suggests monotherapy with cognitive behavioral therapy as initial treatment in patients in the acute phase of mild major depressive disorder (conditional recommendation; low-certainty evidence).ACP suggests one of the following options for patients in the acute phase of moderate to severe major depressive disorder who did not respond to initial treatment with an adequate dose of a second-generation antidepressant: • Switching to or augmenting with cognitive behavioral therapy (conditional recommendation; low-certainty evidence) • Switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment (see Clinical Considerations) (conditional recommendation; low-certainty evidence)The informed decision on the options should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences.