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
"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
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
"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
Weissman stated that the relationship with family history is harder to
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
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
Patients randomized to the medication augmentation did tend to reach
remission and response criteria faster than those in the cognitive-therapy
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
"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. ▪