Cognitive Therapy, Meds Equal in Curbing Depression Relapse

Patients treated for depression who are at high risk for relapse after responding to an acute phase of cognitive therapy (CT) are just as likely to avoid relapse via continuation phase cognitive therapy (C-CT) or by switching to an antidepressant regimen with medication management, new research suggests.

Of 241 at-risk patients randomly assigned to receive 8 months of continuation phase treatment after receiving 12 to 14 weeks of acute-phase CT, 33% of the 69 assigned to pill placebo relapsed into depression compared with approximately 18% of the 86 who went on to receive C-CT and with 18% of the 86 who were switched to continuation phase treatment with the antidepressant fluoxetine.

Robin B. Jarrett, PhD, University of Texas Southwestern Medical Center, in Dallas, and Michael Thase, MD, now at University of Pennsylvania, and colleagues (at the University of Pittsburgh), collaborated on the randomized, controlled trial to extend Dr. Jarrett’s initial finding of C-CT efficacy in preventing relapse relative to an assessment-only control. The finding that receiving C-CT prevented relapse more than pill placebo shows that another site (the University of Pittsburgh) can achieve its preventive effects.

Although the researchers expected that both active therapies would reduce the risk for relapse, they had anticipated that C-CT would have a more durable benefit ― that is, to prevent recurrence during the first year ― compared to the medication comparator. The study was powered for this comparison after active treatments were discontinued.

“Contrary to prediction, we found no evidence to support the hypothesis that C-CT conveys more enduring prophylaxis in acute phase CT responders than fluoxetine after continuation phase treatments are stopped,” the investigators write.

Relapse Predictor

Patients were identified as susceptible to relapse/recurrence by demonstrating a delayed, unstable, or partial response in the acute-treatment-phase CT. The researchers prospectively applied an algorithm from Dr. Jarrett’s earlier study to detect heightened risk, with parameters that included at least 1 rating score of 7 or higher on the 17-item Hamilton Rating Scale for Depression (HRSD-17) during the final 7 weekly assessments. Dr. Thase’s group had also previously shown this effect with a somewhat distinct algorithm.

“Those with the partial remission were viewed to be at high risk for relapse and recurrence, and that finding is basically one of the most robust findings in psychiatry ― that partial remission or unstable remission does forecast a later relapse and recurrence,” Dr. Jarrett told Medscape Medical News.

In an earlier comparison of sequential treatments, with acute-phase antidepressant treatment followed by either a maintenance antidepressant regimen, pill placebo, or a group-based cognitive therapy (Mindfulness-Based Cognitive Therapy), Zindel Segal, PhD, University of Toronto, Canada, and colleagues had also found that medication and cognitive therapy were comparable in reducing relapse/recurrence.

Commenting on the current study for Medscape Medical News, Dr. Siegel, who was a consultant on the Jarrett-Thase trial, said, “The increasing interest in sequential treatment of mood disorder is a response to 2 phenomena ― high rates of medication discontinuation or reduced antidepressant tachyphylaxis and the need to reduce residual risk for relapse/recurrence. Utilizing a sequenced 2-stage treatment algorithm can provide intervention for the acute depressive episode as well as targeted prevention benefits against episode return.”

“To date,” said Dr. Segal, “very few studies have evaluated this model, and the Jarrett et al study provides unique data to address this question. Their finding that C-CT or fluoxetine in acute-phase CT responders provides greater prophylaxis than placebo demonstrates the value of the second step in a sequenced approach.”

Research Gap

The investigators describe their study as being not only the first to demonstrate that an antidepressant medication regimen significantly reduces the risk for relapse/recurrence for patients who first received psychotherapy but also the largest study of relapse prevention strategy applied after acute-phase CT.

“So there was a huge gap in the literature with respect to having psychotherapy first,” Dr. Jarrett elaborated. “Nobody had ever showed that psychotherapy responders would actually accept medication as a way of preventing depression. In addition, patients need an array of choices. Continuation phase cognitive therapy is an effective choice in preventing relapse as an immediate intervention for high-risk responders.”

The question of whether medication intervention would be accepted by patients who initially sought CT did appear to surface in the attrition data from Dr. Jarrett’s study. Although the final attrition rates after 8 months did not statistically differ between the groups, significantly more patients from the medication and placebo combined groups (n = 13) than from the C-CT group (n = 1) left the study before the first continuation-phase session.

Dr. Jarrett noted that this early attrition from those assigned to medication and placebo groups did not affect the final analysis of the superiority of both active treatments relative to placebo, but she explained that “this sample is biased in that the people who went into this study wanted psychotherapy, they wanted cognitive therapy. They didn’t prefer medication, or they would have started with that approach.”

The researchers’ next steps include delving more into the characteristics of risk for depression.