Wednesday, December 4, 2019

Study Raises New Questions About How Best to Reduce Risk of Depression Recurrence

The return of depressive symptoms after treatment has ended is common in a number of patients with major depressive disorder (MDD). A study published today in JAMA Psychiatry found that patients who stopped taking antidepressants after recovery from chronic or recurrent depression had higher rates of recurrence than those who continued the medications. The difference in recurrence was observed regardless of whether the initial recovery was achieved with antidepressant monotherapy or a combination of antidepressants and cognitive-behavioral therapy (CBT).

“Maintenance of antidepressant medication treatment was associated with a reduced risk of depressive recurrence, but previous treatment with cognitive-behavioral therapy was not,” wrote Robert J. DeRubeis, Ph.D., of the University of Pennsylvania and colleagues.

The findings were based on data collected in the second of a two-phase study. In the first phase, the researchers compared outcomes of 452 patients with recurrent or chronic MDD randomly assigned to take antidepressants alone with those assigned to take antidepressant in combination with CBT. Patients who recovered from MDD (defined as 26 consecutive weeks without relapse) were invited to participate in phase 2 of the trial, in which they were randomized to continue antidepressant treatment or withdrawn from antidepressants over several weeks. (Patients who had received combination therapy treatment during phase 1 ended their course of CBT treatment when phase 2 began.) A total of 292 patients who participated in phase 1 of the study consented to participate in phase 2. These patients were then followed for three years.

“Antidepressant medication maintenance was associated with lower rates of recurrence compared with medication withdrawal regardless of whether patients had achieved recovery with monotherapy treatment [antidepressant only] in phase 1 (48.5% with medication maintained vs 74.8%) … or combination therapy treatment (48.5% with medication maintained vs 76.7% with medication withdrawn),” DeRubeis and colleagues wrote. “No evidence was found that the provision of CBT during acute/continuation treatment [in phase 1] provided protection against subsequent recurrence. … If anything, the initial advantage of the combination therapy treatment that was observed in phase 1 appeared to decrease during the phase 2 follow-up period.”

Psychiatrist Marlene P. Freeman, M.D., the Abra Prentice Foundation Chair in Women’s Mental Health at Massachusetts General Hospital, summarized several takeaways from the findings in an accompanying editorial. “This study clearly underscores the benefit of maintenance antidepressant treatment for this population and is in line with the body of maintenance studies of antidepressant medications, in which randomized studies consistently report that continuation of the medication on which remission occurred provides protection against recurrence at higher rates than placebo. This said, as a field we need to address the challenges associated with maintenance use of antidepressant medications.”

The study leaves several important questions unanswered, she noted: “It is not known how the combination therapy group who recovered in phase 1 would have fared if randomized to continue or discontinue treatment with CBT. We also do not know if and how much better the combination therapy would have been in preventing relapse in phase 2, which is important because relapse rates were relatively high, even with medication maintenance.”

For related information, see the Psychiatric News article “Tips for Recognizing, Treating Symptoms of SSRI Discontinuation,” by Madhukar H. Trivedi, M.D., and Manish K. Jha, M.B.B.S.

(Image: iStock/SDI Productions)

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