Symptomatic and Syndromal Anxiety in Chronic Forms of Major Depression: Effect of Nefazodone, Cognitive Behavioral Analysis System of Psychotherapy, and Their Combination

Background: Limited information is available on treatment response of anxiety symptoms in chronic forms of major depression. Concurrent anxiety disorders are prevalent in chronic depression, but the responsiveness of patients with such comorbidity to different treatments is largely unknown. This study investigated the comparative efficacy of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), and their combination in improving anxiety symptoms in patients with chronic forms of major depression, including those with a concurrent anxiety disorder.

Method: 681 patients with chronic major depressive disorder (DSM-IV criteria) participated in a multicenter study of 12 weeks of acute treatment with nefazodone (N=226), CBASP (N=228), or the combination (N=227). The Hamilton Rating Scale for Anxiety (HAM-A), the HAM-A psychic anxiety factor, and the anxiety/arousal subscale of the 30-item Inventory for Depressive Symptomatology-Self Report (IDS-SR-30) were used to assess anxiety symptoms.

Results: In the full sample, without controlling for change in depressive symptoms, combination therapy was superior to both monotherapies on all 3 anxiety measures both in the rate of change and at endpoint. When change in depressive symptoms was controlled for, there were no treatment differences in rate of change from baseline to week 12 on any of the 3 anxiety measures. In those patients with a concurrent anxiety disorder, however, the combination was superior to CBASP on the HAM-A and the IDS-SR-30. Nefazodone alone and combination therapy were both superior to CBASP on the HAM-A psychic anxiety factor.

Conclusion: For patients with chronic depression, combination therapy is superior to CBASP or nefazodone alone. Among patients with a concurrent anxiety disorder, nefazodone, either alone or in combination with CBASP, improves anxiety symptoms faster than CBASP alone, independent of depressive symptom reduction.