Severely Depressed Most Responsive to Combined Cognitive and Drug Rx

Psychiatric TimesVol 31 No 10
Volume 31
Issue 10

Patients with severe depression are more likely to have symptom remission with a combination of cognitive therapy and antidepressant medication than those with less severe or more chronic illness.

A large-scale clinical trial examined outcomes from acute through continuation treatment of depression.1 Patients with severe, nonchronic MDD were more likely to have symptom remission with a combination of cognitive therapy and antidepressant medication than those with less severe or more chronic illness.

Lead author Steven Hollon, PhD, Department of Psychology, Vanderbilt University, told Psychiatric Times that the combination of cognitive therapy with medications had a big effect for patients with severe, nonchronic depression “but was not needed by patients with less severe, nonchronic depression [as] they did well regardless, and did not help patients with chronic depression regardless of severity [as] they did less well regardless.”

Hollon and colleagues recruited 452 patients with chronic or recurrent MDD from 3 university-affiliated outpatient clinics. Participants were randomized to receive personalized antidepressant medication treatment with or without a standardized cognitive therapy. The depressive illness was categorized as chronic if episodes lasted 2 years or longer, or recurrent if an episode had followed another within the past 3 years.

Treatment of both groups continued for up to 19 months to attain remission and for up to 42 months to achieve recovery (defined as remission sustained for 26 consecutive weeks). Changes in depression symptoms were assessed at intervals throughout the study with the 17-item Hamilton Rating Scale for Depression and the Longitudinal Interval Follow-up Evaluation.

Antidepressant medication treatment was personalized for all patients, consistent with best clinical practices. Dosages were increased as rapidly as possible and maintained at maximum tolerated levels for at least 4 weeks. The antidepressant could be switched and/or augmented with adjunctive agents. The Beck model of cognitive therapy was applied following standardized protocol, with 50-minute sessions provided twice weekly for at least 2 weeks, then at least weekly through acute treatment and at least monthly during continuation, with the frequency adjusted to patient needs.

Patients who had severe but nonchronic depression at study entry and received the combination therapy had a better rate of recovery than those who received medication alone (81.3% vs 51.7%). The median recovery rates across all groups who received combination therapy were better than for those who received medication without cognitive therapy (72.6% vs 62.5%). Remission rates were high but were not statistically signficantly different between groups, occurring in 63.6% of patients who received combination treatment and 60.3% with medication. Although median time to remission was shorter with the combination treatment, that difference was also not statistically significant.

“The study shows that different people respond to different treatment combinations,” Hollon remarked. “We clearly need to do more for the patients with chronic depression.”

In an accompanying opinion paper, Michael Thase, MD,2 called this “one of the most important studies undertaken to evaluate the merits of combining psychotherapy and pharmacotherapy for treatment of major depressive disorder.”

Thase distinguished the scale and scope of this study from previous efforts to compare these treatment conditions in smaller randomized clinical trials with typical durations of 8 to 16 weeks, as well as from meta-analyses of these smaller trials. “Meta-analyses of grouped data were not able to identify the clinically important moderating effects of symptom severity and chronicity,” Thase pointed out.

In their pooled analysis of data from 6 smaller studies, Thase and colleagues had also found a stronger effect from combination treatment in patients with more severe depression symptoms. However, he credits the current randomized clinical trial for providing “much stronger evidence of this clinically meaningful patient-by-treatment interaction.”

According to Thase, this study may also explain why others have found only modest benefit from the combined treatment if their populations had skewed toward patients with more mild or chronic depression. He also noted that the approximate two-thirds of patients who had symptom remission across 1 year of therapy corresponded to the STAR*D study findings with sequentially adjusted pharmacotherapy. “It is reassuring that the outcomes in these two studies were so similar across 12 months, especially given the several differences in study design and research aim,” he observed, adding, “such findings are indeed grounds for therapeutic optimism.”

Most patients have access to medication treatment, although the dosage is often too low and the duration too short. “But good cognitive therapy is still hard to find,” Hollon told Psychiatric Times.

Hollon and colleagues acknowledge that the cost is higher for combination treatment than for medication alone. However, they noted that their study did not include a cost-benefit analysis to consider reduced treatment costs from hastening remission and recovery. Even without a formal cost-benefit analysis, however, they suggest that their data support providing combination treatment for patients with more severe and nonchronic depression. “Such a recommendation would be consistent with the goals of personalized medicine,” they write, and “patients are given what they most need, and costly resources are reserved for those likely to benefit from them.”


1. Hollon SD, DeRubeis RJ, Fawcett J, et al. Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Aug 20; [Epub ahead of print].

2. Thase ME. Large-scale study suggests specific indicators for combined cognitive therapy and pharmacotherapy in major depressive disorder. JAMA Psychiatry. 2014 Aug 20; [Epub ahead of print].

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