Combination Therapy Optimizes Recovery in Severe Depression

Caroline Cassels

August 20, 2014

Combination treatment with psychotherapy and antidepressant medication (ADM) appears to optimize rates of recovery in patients with severe, nonchronic major depressive disorder (MDD).

A large-scale, multicenter, randomized clinical trial conducted by investigators at Vanderbilt University in Nashville, Tennessee, showed that patients with severe, nonchronic depression had better rates of recovery if they were treated with cognitive therapy (CT) combined with ADMs compared with patients treated with ADMs alone. However, researchers note that this treatment strategy had little if any benefit for patients with less severe or chronic major depression.

"Combining CT with ADM enhanced the rate of recovery compared with ADM alone in a sample of patients with chronic or recurrent nonpsychotic MDD and minimal exclusions for other psychiatric and medical comorbidities," the researchers, led by Steven D. Hollon, PhD, write.

The study was published online August 20 in JAMA Psychiatry.

Symptom Reduction Not Enough

There is growing consensus that simply reducing depressive symptoms is not enough and that full remission should be the goal of acute treatment, the investigators note.

The most common treatment for depression, antidepressants are particularly recommended for patients with severe forms of the disorder. Although one third of patients achieve remission with any given ADM, half of these patients relapse during continuation treatment before achieving recovery.

Research shows that CT is as effective as antidepressants alone and that combining the 2 increases response rates, with estimates of increased efficacy ranging from 6% to 33%, the investigators add.

The researchers point out that the majority of randomized trials typically test a single antidepressant for a brief duration, whereas patients in a real-world clinical practice can receive treatment as long as necessary, potentially with different agents until remission achieved. Similarly, they note that in clinical trials, CT is also delivered in a time-limited manner, even though patients with major depression typically require longer treatment.

"Studies in which practitioners are not permitted to adapt treatment to meet the needs of the patient likely underestimate what could be achieved using the best clinical practice. We sought to determine whether combining CT with ADM enhances recovery when treatment is personalized," the investigators write.

The study included 453 adult outpatients with chronic or current MDD at 3 university medical centers across the United States.

Patients were randomly assigned to receive either ADM alone (n = 225) or combined treatment of ADM and CT (n = 227). Treatments lasted up to 42 months until recovery was achieved. Remission was defined as 4 consecutive weeks of minimal symptoms, and recovery was defined as another 26 consecutive weeks without relapse.

Results showed that combining CT and ADM significantly improved rates of recovery vs ADM alone, at 72.6% vs 62.5%, respectively. However, the investigators note that the advantage of combined treatment was limited to patients with severe, nonchronic MDD; little benefit was observed for patients with less severe or chronic MDD.

In addition, the dropout rate in the combined treatment group was lower than in the group that received ADM alone (18.9% vs 26.8%). Further, those receiving combination therapy experienced fewer adverse events than those who received ADMs alone, mainly because they experienced less time in an MDD episode, the investigators note.

"Our findings suggest that CT engages different mechanisms than ADM but that it likely does so only in some patients. Identifying these mechanisms may suggest ways to enhance treatment response. Future combinatorial trials should include comparisons with CT alone to examine the viability of each monotherapy, especially given evidence that CT effects persist beyond the end of treatment."

Global Public Health Problem

In an accompanying editorial, Michael Thase, MD, University of Pittsburgh in Pennsylvania, notes that the study results are largely supportive of the value of combination therapy for MDD.

"The study is important because of the topic ― MDD is one of the world's great public health problems and the combination of psychotherapy and pharmacotherapy has long been advocated as a preferred approach to optimize outcomes," Dr. Thase writes.

He adds that this study has several strengths, including its large size, which provides the necessary power to test "both main effects and possible interactions across both short-term and continuation phases of study treatment."

"Although much attention has been given to pharmacotherapy, comparable efforts are needed to develop and test alternate models of psychotherapy," he adds.

The authors' disclosures can be found in the original article. Dr. Thase reports no relevant financial relationships with respect to his editorial.

JAMA Psychiatry. Published online August 20, 2014. Abstract, Editorial


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