Compared with medication alone, the combination of optimized medical treatment and cognitive therapy affected a high rate of recovery for patients with severe, nonchronic major depressive disorder.
Although the combination didn’t significantly benefit patients with less severe or chronic depression, it doubled recovery rates among those with the most severe symptoms. The number needed to treat to achieve one recovery in this group was just three, Steven D. Hollon, Ph.D., and his colleagues reported Aug. 20 in the journal (JAMA Psychiatry 2014 [doi:10.1001/jamapsychiatry.2014.1054]).
The failure to observe a significant benefit among those less severely and chronically depressed patients disappointed, wrote Dr. Hollon, who is the Gertrude Conaway Professor of Psychology at Vanderbilt University, Nashville, Tenn.
But this dichotomy could be employed as a way to pinpoint those most likely to respond to the combination.
"[These moderators] could be used prescriptively to guide a more efficient allocation of treatment resources. Given the higher cost of combined treatment, it might be reserved for patients with nonchronic, more severe depression. Such a recommendation would be consistent with the goals of personalized medicine; patients are given what they most need and costly resources are reserved for those likely to benefit from them."
The 42-month trial randomized 452 patients with chronic or recurrent major depressive disorder to optimized antidepressant treatment or antidepressants plus cognitive therapy. They were a mean of 43 years old with a mean score of 22 on the Hamilton Rating Scale for Depression (HRSD). Recurrent depression was present in 83%; chronic, in 35%. The overall dropout rate was 23%, but attrition was significantly lower in the combination group (19% vs. 27%).
Overall, the rates of remission did not significantly differ between the groups. However, recovery was significantly more common among those who had the combination therapy (73% vs. 63%; hazard ratio, 1.33), with a number needed to treat of 10.
An exploratory analysis determined that the timing of depression and its severity significantly influenced outcomes. Among those with either less severe depression or high-severity chronic depression, the treatment effect was small. But among those with severe, nonchronic depression, a significant benefit was found. The recovery rate for these patients was significantly higher with combination therapy (81% vs. 52%; HR, 2.34), with a number needed to treat of three.
Patients in the combination treatment group also experienced significantly fewer serious adverse events, probably because they spent less time in major depressive episodes, the authors suggested.
Dr. Hollon reported no financial disclosures. However, his coauthors reported relationships with multiple pharmaceutical companies. The National Institutes of Mental Health funded the study. Wyeth Pharmaceuticals and Pfizer provided some study medications.
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