Evidence-Based Applications of Combination Psychotherapy and Pharmacotherapy for Depression.

Combination treatment with psychotherapy and antidepressant medication can be provided from the initiation of treatment, sequentially after nonremission with a single-modality treatment or sequentially after remission to buttress the patient's recovery to prevent recurrence. Combination treatment from the initiation of care is best reserved for patients with high depression severity. Sequential addition of treatments, particularly psychotherapy after nonremission to antidepressant medication, is the best supported method of combination, improving remission rates and reducing relapse and recurrence in the long term. However, uncertainty persists around the optimal form of psychotherapy to combine with antidepressant medication for maximizing long-term gains. Better outcomes from combination treatment have been strongest in clinical trials that limited pharmacotherapy to a single antidepressant; benefits of combination treatment have been substantially smaller in trials that allowed flexible use of multiple antidepressant classes. Patients with recurrent major depressive disorder who benefit from combination treatment have better long-term outcomes if an active treatment component is maintained during recovery.