Cognitive Therapy for Depression Effective Alternative Treatment

Less than one-third of subjects in a federally funded study of depression treatment consented to try cognitive therapy after discontinuing the antidepressant citalopram either because the medication was not effective or because side effects were intolerable. However, the outcomes among those who did consent to cognitive therapy and who were ultimately randomized into it proved to be comparable to those of all the pharmaceutical options.

Those were the findings from two reports in the May American Journal of Psychiatry on the Sequenced Treatment Alternatives to Relieve Depression (STAR^*D) study. The six-year multi-level study began with 2,876 patients; of those, one-third achieved remission—the near absence of any depressive symptoms—and an additional 10 percent to 15 percent were deemed responders. Level 2 consisted of 1,439 eligible patients who did not experience remission in level 1 (Psychiatric News, January 20, 2006; April 21, 2006; July 7, 2006; September 15, 2006; November 17, 2006).

Using a study-design strategy known as “equipoise stratified design,” patients in level 2 could indicate from a menu of treatment options which ones were acceptable or unacceptable prior to randomization. Options included cognitive therapy alone or in combination with the level 1 treatment (which was citalopram for all subjects), augmentation of citalopram with bupropion or buspirone, or replacement of citalopram with sertraline, bupropion, or venlafaxine.

Of the 1,439 participants who entered level 2, only 1 percent were willing to be randomized into all of the treatment options. Twenty-six percent were willing to be randomized into a treatment involving cognitive therapy, either alone or as an augmentation to citalopram.

Remission rates were similar in the 12-week study regardless of what treatment was chosen: 25 percent for the patients who switched to cognitive therapy and 23 percent for those who received it as augmentation.

For those continuing on citalopram, pharmacologic augmentation resulted in significantly more rapid remission than augmentation with cognitive But those who discontinued citalopram in favor of another medication had significantly more side effects than those who switched to cognitive therapy alone, according to the report.

“For patients who would consider psychotherapy as a reasonable alternative, it worked as well as switching antidepressants,” the lead author of the treatment outcome study, Michael Thase, M.D., told Psychiatric News. “The up side of picking psychotherapy over a different medication is the relative absence of side effects. For the patients who wanted to stick to medication, there appears to have been a benefit over psychotherapy in terms of speed of treatment efficacy.”

Thase was a professor of psychiatry at the University of Pittsburgh Medical Center and the Western Psychiatric Institute and Clinic when the STAR^*D study was conducted. He recently joined the faculty of the University of Pennsylvania School of Medicine and the Philadelphia Veterans Affairs Medical Center.

He cautioned that the design of the study may limit the generalizability of the findings regarding patient preferences, which contradicts other studies that have found psychotherapy in general and cognitive therapy in particular to be at least as acceptable to patients as antidepressant medications.

He noted, for instance, that to be included in the study, patients had to have first been on citalopram, a fact that may have excluded individuals who might naturally favor a psychotherapeutic approach.

“The fact that it was a second-step study of patients who were first on medication may have screened out patients who were zealous about psychotherapy,” Thase told Psychiatric News.

Moreover, he said, there was a financial disincentive to choosing psychotherapy since medication costs were covered by the study, but copays associated with cognitive therapy were not; the copays were deemed to be the patient's responsibility as part of insurance contracts, Thase explained.

Still, Thase said the results suggest that some modifications to the way cognitive therapy is delivered could enhance its acceptability to patients. For instance, therapists might choose to focus on symptom relief—such as relief from insomnia—since a preference for medication may reflect a greater patient focus on those aspects of recovery from depression, he said.

“Another interesting future direction is to use 21st-century technological developments such as the Internet and DVD to make the therapy more broadly accessible, thereby unlinking it from the necessity of seeing a therapist twice a week in an office,” Thase told Psychiatric News.

The report on patient preferences appeared in “Acceptability of Second-Step Treatments to Depressed Outpatients: A STAR^*D Report,” with lead author Stephen Wisniewski, PhD., a professor of epidemiology at the University of Pittsburgh School of Public Health.

Demographic analysis revealed that patients who accepted cognitive therapy as an option had more education and were more likely to have a family history of mood disorder than patients who did not include cognitive therapy among possible treatments.

“Since education is associated with income, it is possible that this finding is a reflection of the need to pay for cognitive therapy not covered by insurance,” wrote Myrna Weissman, Ph.D., in an editorial accompanying the two study reports. “Higher income patients may have had better insurance coverage and might not have incurred much or any out-of-pocket expense.”

Weissman stated that the relationship with family history is harder to interpret.

She also emphasized the methodogical problems cited by Thase and noted that it could not be concluded from the results that depressed patients do not want cognitive therapy.

In the treatment outcome report, “Cognitive Therapy as a Second-Step Treatment: A STAR^*D Report,” Thase and colleagues compared outcomes and adverse events among the following randomized groups:

Patients who indicated a willingness to enter a certain kind of treatment in the Wisniewski study were not necessarily randomized into that treatment. Moreover, those patients who indicated that they would consider only cognitive therapy or only medication were excluded from analysis in the treatment study since their predisposition toward that treatment may have biased the outcome results, Thase explained.

The investigators found no significant differences between groups in the proportion of participants who achieved remission according to the 17-item Hamilton Rating Scale for Depression or in the percentages of those who achieved remission or response as assessed by the 16-item Quick Inventory of Depressive Symptomatology.

Patients randomized to the medication augmentation did tend to reach remission and response criteria faster than those in the cognitive-therapy augmentation condition.

There were large differences between the switch treatments in measures of frequency, intensity, and burden of medication side effects. Forty-eight percent of the patients randomized to a second course of antidepressant therapy reported at least a moderate degree of side-effect intensity, and 34 percent reported at least a moderate level of side-effect burden, compared with none of the patients in the cognitive-therapy switch arm.

The STAR^*D study is supported by the National Institute of Mental Health. The following pharmaceutical companies provided medications at no cost for the study: Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth-Ayerst Laboratories.

“Cognitive Therapy as a Second-Step Treatment: A STAR^*D Report,” “Which Second Step Treatments Are Acceptable to Depressed Outpatients? A STAR^*D Report,” and“ Cognitive Therapy and Interpersonal Psychotherapy: 30 Years Later” can be accessed at<http://ajp.psychiatryonline.org/?> under the May issue. ▪