University Medical Center|
Chronic Depression: Two Therapies Are Better than One
STANFORD -- Conventional wisdom among psychiatrists has dictated that people
suffering from chronic depression are best treated with a combination of
antidepressants and psychotherapy. Now, a large national study confirms that
combination therapy is more effective than either medication or counseling
The study, published May 18 in the New England Journal of Medicine, shows that
the antidepressant Serzone combined with psychotherapy specifically designed for
chronic depression offers the best treatment for people suffering from this
long-term form of depression.
This study is the largest ever undertaken comparing medication alone,
psychotherapy alone, or combination treatment for chronic depression, according
to the researchers. Bristol-Myers Squibb Co., makers of Serzone, funded the
"This is really a landmark study," said study co-author Bruce Arnow,
PhD, assistant professor of psychiatry and behavioral sciences at Stanford
University Medical Center. "This is the first study that's been large
enough to adequately test whether combination treatment is truly superior to
medication or psychotherapy alone."
In the study, 681 depressed patients were randomly assigned to one of three
treatment options. Patients assigned to the drug-only group took Serzone alone,
therapy-only patients received psychotherapy tailored to chronic depression, and
combination patients were given both simultaneously. After 12 weeks,
significantly more patients who received the combination of therapies had
improved compared with patients receiving either single treatment.
At any given time, 3 percent of the U.S. population suffers from chronic
depression. With chronic depression, patients may suffer from episodes of acute
depression but never fully recover between episodes. Chronically depressed
individuals are hospitalized more frequently, require more health care, and
attempt suicide more frequently than those suffering from episodic depression.
They have more severe problems with work, family and social relationships.
Depression has been estimated to cost the American economy $53 billion per year.
In their paper, the researchers assert that "chronic depression accounts
for an inordinate portion of the enormous illness burden associated with
"It's a major public health problem in this country," Arnow said,
"and this [study] sheds important light on the most appropriate treatment
for this group of patients."
Study participants included adult men and women of varying ages who scored 20 or
greater on the Hamilton Rating Scale for Depression (HAM-D). The HAM-D assesses
the severity of depression in patients who are already diagnosed with
depression. The higher the score, the more severe the depression. A score of
below 8 is considered normal; the average score of patients at the start of the
study was 27.
Among patients who completed 12 weeks of combination therapy, 85 percent reduced
their HAM-D score by at least half. For both drug-only and therapy-only
patients, only about 50 percent reduced their score by that much.
"Patients in this study had been suffering major depression for an average
of eight years," Arnow noted. "Many had been suffering for 20 years or
more, so the response to combination treatment of 12 weeks is very
The psychotherapy used in the study, Cognitive Behavioral Analysis System of
Psychotherapy, or CBASP, is the first psychotherapy developed specifically to
treat chronic depression. It teaches patients to focus on how their thinking and
behavior affect their interpersonal interactions and to apply a specific
problem-solving technique to improve their functioning in interpersonal
Few therapists are trained in CBASP, however, and Arnow hopes the results of
this study will spur efforts to provide psychotherapists with more opportunities
to learn it, making it more widely available.
The antidepressant studied, Serzone, used alone or in combination with
psychotherapy, was associated with an earlier response than psychotherapy alone.
Patients did not experience significant sexual dysfunction or weight gain, which
are frequent side effects of antidepressant medications. Fewer side effects mean
that patients are more willing to continue taking the drug for longer periods.
The results for both single treatments were comparable to those found for
antidepressants in prior studies of patients with chronic depression. However,
Arnow noted, the results of the current study cannot be generalized to other
antidepressants used in combination with psychotherapy or forms of psychotherapy
other than CBASP until they have been tested in clinical trials and shown
similar response rates.
The study also included a four-month continuation trial for patients who
responded to medication alone, psychotherapy alone or combination treatment.
This was followed by a 52-week maintenance phase evaluating for some patients
the drug versus placebo and for others monthly psychotherapy. The data from
these two phases of the study are still being evaluated.
Besides its large size, a key strength of the study is that researchers at all
sites found the same results, Arnow said.
"The same pattern of the two monotherapies being about equal and the
combination proving superior was true at all sites," he said. "The
fact that the pattern of results didn't vary from site to site make the findings
all the more compelling."
In addition to Arnow, contributing researchers at Stanford include Alan
Schatzberg, MD, professor and chair of psychiatry and behavioral science; Rachel
Manber, MD, assistant professor of psychiatry and behavioral science; and Lorrin
Koran, MD, professor of psychiatry and behavioral science.
Other study sites included Brown University; Medical College of Virginia &
Virginia Commonwealth University; State University of New York, Stonybrook;
Cornell University Medical College; Emory University School of Medicine;
University of Texas Medical Branch at Galveston; University of Texas
Southwestern Medical Center at Dallas; Rush-Presbyterian-St. Luke's Medical
Center, Chicago; University of Washington, Seattle; University of Arizona,
Tucson; and Western Psychiatric Institution and Clinic, University of
Many of the principal investigators in the multi-study were consultants and
received honorariums from Bristol-Myers Squibb or serve on the company's
scientific advisory board. Most of these researchers also have similar
relationships with other firms that manufacture FDA-approved treatments for
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