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Withdrawing antidepressants tied to higher risk of depression recurrence, even with continued CBT

December 12, 2019

By David Douglas

NEW YORK (Reuters Health) - Withdrawing antidepressant drugs in people who have recovered from a chronic or recurrent major depressive episode during pharmacologic treatment alone or in combination with cognitive-behavioral therapy (CBT) is linked with a higher recurrence risk, even with continued CBT, according to a new clinical trial.

"Consistent with a large body of previous research, patients with depression who recovered with antidepressant medication were better protected against the return of symptoms if they remained on the medication, compared to those who were tapered off of their medication," said Dr. Robert J. DeRubeis of the University of Pennsylvania, in Philadelphia.

"On the other hand," he told Reuters Health by email, "the preventive effects of CBT for depression, well-documented in previous research, was not evident in this study."

In a phase-2 trial, Dr. DeRubeis and colleagues randomized 292 outpatients to either continue receiving or be withdrawn from antidepressant medications after they recovered from a chronic or recurrent major depressive episode with antidepressant medication alone or in combination with CBT during phase 1 of the study. Patients who had been receiving CBT in phase 1 continued doing so in phase 2.

Over a three-year follow-up, medication maintenance was associated with lower rates of recurrence compared with medication withdrawal, regardless of whether patients had been on medication alone in phase 1 (48.5% vs. 74.8%, P=0.002) or on combination therapy (48.5% vs. 76.7%, P

Maintenance of medication was significantly associated with sustained recovery (odds ratio, 2.54).

Dr. DeRubeis noted that he and his colleagues "were surprised by the absence of a preventive effect of CBT. We think it is vital for future research to ask whether preventive effects of CBT for depression are suppressed by the concurrent use of medication, as has been shown in studies of CBT for anxiety disorders."

In an accompanying editorial Dr. Marlene P. Freeman of Harvard Medical School, in Boston, cautions that "An important limitation of the study was that medication discontinuation was not placebo-controlled."

Nevertheless, she told Reuters Health by email, "This study underscores that for many individuals major depressive disorder is a long-term condition requiring ongoing attentive treatment. In fact, for many patients, multiple treatment modalities are required for successful treatment."

"As we consider issues such as access to mental-health care," Dr. Freeman concluded, "it is important that we consider not only acute treatment, but also long-term needs of patients. Depression and other psychiatric disorders are often chronic, and treatment needs have to take into account that care and resources are required for patients to recover and remain in remission."

The study did not have commercial funding, but Wyeth Pharmaceuticals provided venlafaxine, and Pfizer provided sertraline. Several of Dr. DeRubeis' coauthors report ties to antidepressant makers.

SOURCE: and JAMA Psychiatry, online December 4, 2019.

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