Psychotherapy and Antidepressants Combo Prevents Depressive Episode Recurrence

Robert J. DeRubeis, PhD

A combination of antidepressants and cognitive behavioral therapy (CBT) could be the answer in treating major depressive disorder (MDD) by eliminating the recurrence of depressive episodes.

Investigators, led by Robert J. DeRubeis, PhD, Department of Psychology, University of Pennsylvania, examined the effects of combining CBT with antidepressant medications on the prevention of depressive recurrence when antidepressants are withdrawn or maintained following recovery from MDD.

The phase 2 randomized trial included 292 patients with MDD who previously participated in a phase 1 trial and have recovered from chronic or recurrent major depressive episodes with either antidepressant medication alone or in combination with CBT.

“In this study, maintenance monotherapy was associated with reduced rates of depressive recurrence,” the authors wrote. “When CBT was provided in the absence of monotherapy treatment, a preventive effect on depressive relapse was noted.”

In the phase 2 trial, the patients were randomized to receive maintenance or withdrawal of treatment with antidepressant medications. Each patient was followed for 3 years.

The trial was conducted in research clinics in 3 university medical centers in the US.

The main outcomes and measures was a recurrence of an MDD using longitudinal interval follow-up evaluations and sustained recovery.

The investigators found that those withdrawing from antidepressant medications were linked to higher rates of recurrence than those with maintenance of antidepressant medication treatment regardless of whether patients achieved recovery with or without acute cognitive behavioral therapy treatment.

Overall, antidepressant medication maintenance was linked to lower rates of recurrence than medication withdrawal regardless of whether patients achieved recovery with monotherapy treatment in phase 1 (48.5% with medication maintained vs 74.8% with medication withdrawn; z&thinsp;=&thinsp;−3.16; P&thinsp;=&thinsp;.002; number needed to treat [NNT], 2.8; 95% CI, 1.8-7.0) or combination therapy treatment (48.5% with medication maintained vs 76.7% with medication withdrawn; z&thinsp;=&thinsp;−3.49; P&thinsp;<&thinsp;.001; NNT, 2.7; 95% CI, 1.9-5.9).

Maintenance compared with withdrawal of medication was associated with sustained recovery rates (z&thinsp;=&thinsp;2.90; P&thinsp;=&thinsp;.004; OR, 2.54; 95% CI, 1.37-4.84; NNT, 2.3; 95% CI, 1.5-6.4).

They also found the interaction of phase 1 and phase 2 treatment conditions did not have a significant association with sustained recovery (z&thinsp;=&thinsp;.30; P&thinsp;=&thinsp;.77; OR, 1.14; 95% CI, .49-2.88).

“Maintenance of antidepressant medication treatment was associated with a reduced risk of depressive recurrence, but previous treatment with cognitive behavioral therapy was not,” the authors wrote. “Whether cognitive behavioral therapy has a similar protective effect or whether adding antidepressant medications to cognitive behavioral therapy treatment interferes with any such protective effect remains unclear.”

Previous research has demonstrated that antidepressant medications and CBT have similar efficacies on acute outcomes for patients with MDD. The combination of the 2 forms of treatment is linked with better acute outcomes than either treatment modality alone.

However, a substantial proportion of patients with MDD experience a chronic or recurring course.

Acute treatment with antidepressant medications has not been linked to the prevention of recurrence or relapse, while continuing or maintaining antidepressant medication regimens for patients has been associated with forestalling symptom return.

Cognitive behavioral therapy, when delivered alone, appears to be associated with relapse prevention, but less is known about this relationship.

The study, "Prevention of Recurrence After Recovery From a Major Depressive Episode With Antidepressant Medication Alone or in Combination With Cognitive Behavioral Therapy," was published online in JAMA Psychiatry.