News Release

Therapy plus antidepressants help patients with severe, nonchronic depression

Peer-Reviewed Publication

JAMA Network

Bottom Line: Patients with severe, nonchronic depression had better rates of recovery if they were treated with cognitive therapy (CT) combined with antidepressant medication (ADM) compared to ADMs alone.

Authors: Steven D. Hollon Ph.D., of Vanderbilt University, Nashville, Tenn., and colleagues.

Background: There is a growing consensus that reducing depressive symptoms isn't enough and that a return to full normalization should be the goal. ADM is the most common treatment for depression, especially when the condition is more severe.

How the Study Was Conducted: The authors conducted a randomized clinical trial with 452 adult outpatients with chronic or recurrent major depressive disorder (MDD) at three university medical centers in Philadelphia, Chicago and Nashville. The patients were treated either with ADM alone (n=225) or a combined treatment of CT and ADM (n=227). Treatments lasted for up to 42 months until recovery was achieved. Remission was defined as four consecutive weeks of minimal symptoms and recovery was defined as another 26 consecutive weeks without relapse.

Results: A combined treatment of CT plus ADM improved rates of recovery compared to ADMs alone (72.6 percent vs. 62.5 percent) but the main effects of treatment on recovery were impacted by severity and the chronic nature of the condition. The advantage for combined treatment was limited to patients with severe, nonchronic depression (n=146) (81.3 percent vs. 51.7 percent). Recovery rates were similar among the two groups for patients with less severe MDD or chronic MDD. Patients who underwent combined treatment also reported fewer serious adverse events than patients treated with ADMs alone but this was largely due to less time spent in an MDD episode.

Discussion: "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."

(JAMA Psychiatry. Published online August 20, 2014. doi:10.1001/jamapsychiatry.2014.1054. Available pre-embargo to the media at

Editor's Note: Authors made conflict of interest disclosures. This study was supported by grants from the National Institute of Mental Health. Wyeth Pharmaceuticals and Pfizer Inc. provided medications for the trial. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Indicators for Combined Therapy, Medication Treatment for Depression

In a related editorial, Michael E. Thase, M.D., of the University of Pennsylvania, Philadelphia, writes: "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 – and the approach taken, a large-scale (n=452), 3-center study with adequate power to test both main effects and possible interactions across both short-term and continuation phases of study treatment."

"The main findings are largely supportive of the value of combined treatment for MDD: patients receiving CT in addition to pharmacotherapy were significantly more likely to recover than were the patients who received pharmacotherapy alone," Thase notes.

"Specifically, combined treatment was more effective for patients with higher symptom levels and less effective for those with more chronic episodes … By contrast combined treatment provided no advantage over pharmacotherapy alone for the subsets of patients with milder depressions and with more chronic depressions, who did as well with pharmacotherapy alone," Thase writes.


(JAMA Psychiatry. Published online August 20, 2014. doi:10.1001/jamapsychiatry.2014.1524. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Media Advisory: To contact author Steven D. Hollon, Ph.D., call David Salisbury 615-322-6397 or email To contact editorial author Michael E. Thase, M.D., call Lee-Ann Donegan at 215-349-5660 or email

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