Sequential Treatment Can Reduce Risk of Relapse and Recurrence in Major Depressive Disorder

Sequential Treatment Can Reduce Risk of Relapse and Recurrence in Major Depressive Disorder

May 24, 2021

Sequential integration of psychotherapy and pharmacotherapy is a viable strategy for preventing relapse and recurrence in major depressive disorder.

Sequential Treatment of MDD Reduces Risk of Relapse

According to a systematic review and meta-analysis of 17 clinical trials published in JAMA Psychiatry, integrating psychotherapy after pharmacotherapy reduces relapse in major depressive disorder (MDD).

“The sequential model emerged from the awareness that the persistence of residual symptoms and the frequent occurrence of psychiatric comorbidity were both associated with poor long-term outcome of major depressive disorder (MDD),” explained Jenny Guidi, PhD, University of Bologna, Italy; and Giovanni A. Fava, MD, State University of New York, Buffalo, New York, on the importance of researching outcomes after sequential treatment.1

Researchers hoped to determine if the sequential combination of pharmacotherapy and psychotherapy can reduce the risk of relapse and recurrence in patients with MDD. To do this, they conducted a meta-analysis and systemic review of 17 randomized clinical trials. A total of 2283 participants were included, with 1208 patients receiving sequential treatment and 1075 patients in a control arm.1

The primary outcomes were relapse or recurrence rates of MDD at the longest available follow-up. Independent reviewers conducted data extraction and methodologic quality assessment. The pooled risk ratio for relapse or recurrence of MDD was 0.84 (95% CI 0.74-0.94), suggesting a relative advantage for the sequential treatment arm in preventing relapse or recurrence compared to the control arm.1

The findings of the systematic review and meta-analysis found that sequentially integrating psychotherapy following response to acute-phase pharmacotherapy, alone or combined with antidepressant medication, was associated with a reduced risk of relapse and recurrence in MDD.1

“The sequential model introduces a conceptual shift in clinical practice, and discontinuation of antidepressant drugs may be feasible when a sequential treatment model is used,” wrote Drs Guidi and Fava.1


Guidi J, Fava GA. Sequential combination of pharmacotherapy and psychotherapy in major depressive disorder: a systematic review and meta-analysis. JAMA Psychiatry. 2021;78(3):261-269. doi:10.1001/jamapsychiatry.2020.3650