Preventive cognitive therapy is an effective alternative and addition to antidepressants for preventing depression relapse, study finds

Maintenance treatment with antidepressants was not superior to preventive cognitive therapy after remission or recovery of major depressive disorder, but adding preventive cognitive therapy to antidepressant therapy was superior to antidepressant therapy alone.


Preventive cognitive therapy was as effective as antidepressants for preventing depression relapse and, when combined with antidepressants, was more effective than antidepressants alone, according to a recent study.

Researchers in the Netherlands performed a single-blind, multicenter, parallel, randomized controlled trial to compare the effectiveness of antidepressants and preventive cognitive therapy, alone or in combination, for preventing depression relapse and recurrence. Patients who had previously had at least two depressive episodes, who were in remission or recovery, and who had been taking antidepressants for at least six months were randomly assigned to receive preventive cognitive therapy plus antidepressants, antidepressants alone, or preventive cognitive therapy with tapering of antidepressants. The primary outcome of the study was time-related proportion of patients whose depression recurred or relapsed in the intention-to-treat population, which was assessed four times over 24 months. Results were published online April 3 by Lancet Psychiatry.

A total of 289 participants, 65% of whom were women, were randomly assigned to treatment between July 14, 2009, and April 30, 2015. One hundred four were assigned to preventive cognitive therapy and antidepressant therapy, 100 were assigned to antidepressant therapy alone, and 85 were assigned to preventive cognitive therapy with tapering of antidepressant therapy. The researchers found that antidepressants alone were not superior to preventive cognitive therapy with tapering for relapse or recurrence risk (hazard ratio, 0.86; P=0.502). When preventive cognitive therapy was added to antidepressant therapy, there was a 41% relative risk reduction versus antidepressants alone (hazard ratio, 0.59; P=0.026). Recurrence risk was also lower in those receiving combined treatment than in those receiving preventive cognitive therapy with tapering (hazard ratio, 0.54; P=0.011). Over 24 months of follow-up, two suicide attempts occurred, one each in the antidepressant alone group and one in the preventive cognitive therapy plus tapering group. One patient in the preventive cognitive therapy and antidepressant therapy group died. None of these events were considered to be related to the study interventions.

The researchers noted that their study involved only patients who had had at least two previous depressive episodes and that the effects of different antidepressants could not be determined because most of the participants were taking selective serotonin reuptake inhibitors (SSRIs), among other limitations. However, they concluded that maintenance treatment with antidepressants is not superior to preventive cognitive therapy after remission or recovery of major depressive disorder but that adding preventive cognitive therapy to antidepressant therapy is superior to antidepressant therapy alone.

“Our findings suggest that [preventive cognitive therapy] while tapering off antidepressants might be an alternative strategy to long-term continuation of antidepressants in individuals who wish to stop medication after recovery,” the researchers wrote. They recommended that preventive cognitive therapy be offered to this group as well as to patients with recurrent depression who are receiving maintenance antidepressant treatment.

The author of an accompanying comment noted that stopping antidepressants, especially SSRIs, often leads to withdrawal symptoms and that it is not clear how many patients in the tapering group were experiencing such symptoms rather than undergoing relapse. He also pointed out that augmenting or switching treatment strategies to prevent the return of depressive symptoms during maintenance antidepressant therapy can sometimes be harmful.

The comment author recommended development and testing of additional alternatives to maintenance therapy, including sequential use of psychotherapeutic techniques or other pharmacologic regimens. “The long-term outcomes of depression might be unsatisfactory, not because technical interventions are missing, but because our conceptual models and thinking are inadequate,” the comment author wrote.