Sequential pharmacotherapy, psychotherapy effective against major depressive disorder

In patients with major depressive disorder (MDD), sequential integration of psychotherapy after response to acute-phase pharmacotherapy, alone or combined with antidepressant medication, is significantly associated with reduced risk of relapse and recurrence, compared with standard care, according to a new study.

The systematic review and meta-analysis by Italian researchers was reported by JAMA Psychiatry, online Nov. 25.

The meta-analysis encompassed 17 randomized clinical trials (RCTs) totaling 2,283 participants.

The authors defined the sequential model as an intensive, two-stage approach that derives from the awareness that one course of treatment, whether with pharmacotherapy or with psychotherapy, “is unlikely to entail solutions to the affective disturbances of patients….”

They conclude that the sequential approach

appears to be an effective strategy that yields enduring results in the prevention of the vexing problems of relapse and recurrence.”

MDD’s “chronic and recurrent nature … represents a major clinical challenge. Prevention of relapse and recurrence appears to be a crucial task for successful treatment,” the authors write.

Across all of the underlying RCTs, the participants’ mean age was 45, and 69% were female. All of the studies involved variations of cognitive behavioral therapy.

Length of follow-up in the underlying studies ranged from seven months to 10 years after treatment or randomization. The meta-analysis’ primary outcome was the collective relapse/recurrence rates of the 17 studies.

In each of the underlying studies, the sequential approach was assessed compared with “treatment as usual,” that is, the standard care provided by that agency, with or without clinical management (monitoring drug administration and providing limited support), psychoeducation without specific psychotherapeutic techniques, and/or antidepressant medication (ADM).

The authors point out that clinical guidelines for MDD often recommend long-term treatment with antidepressant medications to prevent relapse, as well as “additional psychotherapy for patients with depression who are at significant risk of relapse, such as those with more previous depressive episodes or who still have residual symptoms.”

The overall pooled risk ratio for relapse/recurrence in the 17 studies was 0.835 (95% CI, 0.743–0.938). The risk ratios for the subgroups of RCTs with continuation of ADM and after discontinuation of ADM were 0.821 and 0.860, respectively.

Corresponding author Jenny Guidi, Ph.D., of the University of Bologna, Italy, said the number of RCTs published on the sequential model over the years has grown steadily, such that a preliminary meta-analysis, in 2011, included eight, and the second meta-analysis, in 2016, included 13. (She was a co-author on both of these.)

The evidence from this latest meta-analysis, Dr. Guidi told eHealthcare Solutions, “provides further support … on the effectiveness of the sequential approach in the prevention of relapse and recurrence in MDD.”

Dr. Joshua E.J. Buckman, senior clinical research fellow at the Centre for Outcomes Research and Effectiveness, University College London, told eHealthcare Solutions, “This study provides a useful update on the previous meta-analysis of treatment sequencing, and highlights a potentially important route to improve the clinical outcomes of depressed patients.”

He cautioned that the evidence base is limited by both a small number of trials and the relatively small study populations. These ranged from 40 to 414; eight studies had enrolled fewer than 100 participants.)

Still, Dr. Buckman said, “there appears to be a benefit to introducing a psychological therapy at the end of acute phase pharmacotherapy. This could be particularly valuable to patients as treatment practices are trending towards those with a history of recurrent or chronic depression being prescribed maintenance pharmacotherapies indefinitely, in order to mitigate their risk of relapse.”

Co-author Dr. Giovanni A. Fava has written a book on well-being therapy, for which he receives no royalties. The authors reported no other disclosures.

No specific funding for the study was reported.