Researchers at Brown University School of Medicine have documented what clinical experience has suggested for some time. In treating patients with the chronic form of major depression, the combination of pharmacotherapy and psychotherapy gives the patient the most significant advantage in overcoming the often debilitating disorder.

Martin B. Keller, M.D., professor and chair in the department of psychiatry and human behavior at Brown, and his colleagues randomly assigned nearly 700 patients to one of three groups: pharmacotherapy alone, psychotherapy alone, or both pharmacotherapy and psychotherapy. They report their findings in the May 18 New England Journal of Medicine.

The patients in the study were between 18 and 75 years old with a score of at least 20 on the 24-item Hamilton Rating Scale for Depression (Ham-D). The researchers excluded subjects if they had any comorbid psychiatric illness or any major medical illness. In addition, patients could not have received any psychoactive medication, electroconvulsive therapy, or cognitive-behavioral psychotherapy within six months of entering the study.

The patients in the medication-only group received up to 600 mg daily of the serotonin and norepinephrine blocker nefazodone for the 12-week study. Dosing began at 200 mg a day and was titrated upward.

Those in the psychotherapy cohort attended two sessions a week for the first four weeks of the study, then one session a week through the remainder of the 12 weeks. This cognitive-behavioral modality employs many behavioral, cognitive, and interpersonal techniques to teach patients to focus on the consequences of their behavior and uses a social-problem-solving technique to address difficulties in interpersonal relationships.

The rate of response in the nefazodone group was 55 percent, while 52 percent of those receiving only psychotherapy responded. For those receiving both pharmacotherapy and psychotherapy, 85 percent showed positive response. A response was defined as either remission (Ham-D score of no more than 8 at both weeks 10 and 12) or a "satisfactory therapeutic response," which the researchers defined as at least a 50 percent reduction in subjects’ Ham-D score resulting in a total Ham-D score of less than 15.

The authors note that nefazodone produced an effect more rapidly than psychotherapy; however, psychotherapy had a greater effect in the long run. By the end of the 12 weeks, the two therapies were nearly identical.

Keller was careful to note that the study was limited by the lack of a placebo for comparison, as well as by the inability to mask patients and therapists in the groups receiving psychotherapy.

In an editorial accompanying the article, Jan Scott, M.D., of Gartnavel Royal Hospital in Glasgow, Scotland, notes that the study is difficult to translate into the clinical setting due to the limitation of only 12 weeks of treatment. "Concentrating on the short-term outcomes creates a snapshot of depression and its treatment," she suggested, "that is not easy to reconcile with the realities of clinical practice."

Scott also pointed out that the study excluded patients with comorbid psychiatric disorders, such as substance abuse or severe personality disorders. According to Scott, the feasibility of combining pharmacotherapy and psychotherapy for chronic depression depends on the clinical population being treated. Although including a group in the study with coexisting psychiatric disorders may have reduced the effect seen, she believes it would not have eliminated it. And, she noted, the study population would then have been closer to mirroring the clinical population.

Scott observed that although establishing the relative efficacy of pharmacotherapy versus psychotherapy has been difficult, this study does help to highlight a growing treatment trend that is generally backed up by clinical experience.