When it comes to treating bipolar depression, a mood stabilizer alone seems
to be just as effective as a mood stabilizer combined with an
Moreover, pharmacotherapy coupled with nine months of psychotherapy for
bipolar depression seems to be more efficacious than pharmacotherapy combined
with a brief psychosocial intervention.
The first result was posted on the New England Journal of Medicine
Web site on March 28; the latter was published in the April Archives of
General Psychiatry. Both investigations were headed by Gary Sachs, M.D.,
a professor of psychiatry at Harvard University.
The findings are also the latest to emerge from the large, multisite
Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a $27
million clinical trial funded by the National Institute of Mental Health
(Psychiatric News, March 3, 2006). "STEP-BD is helping us
identify the best tools—both medications and psychosocial
treatments—that patients and their clinicians can use to battle the
symptoms of this illness," NIMH Director Thomas Insel, M.D., said in a
press release accompanying the latest findings.
Although episodes of depression are the most common cause of disability
among persons with bipolar disorder, and while antidepressants in conjunction
with mood stabilizers are commonly used to treat bipolar depression, there is
only limited evidence of their short-term or long-term efficacy. So in their
first investigation, Sachs and his team randomly assigned 366 bipolar patients
who were experiencing a depression to receive up to 26 weeks of either a mood
stabilizer plus an antidepressant or a mood stabilizer plus a placebo.
The antidepressants used were paroxetine and bupropion since both are
associated with low rates of switching patients to mania early in the course
of treatment and are the antidepressants most commonly prescribed for bipolar
depression. Mood stabilizers were initially limited to lithium, valproate, a
combination of lithium and valproate, or carbamazepine.
In 2004 the protocol was amended to define mood stabilizers as any
antimanic drug approved by the Food and Drug Administration.
The scientists then looked to see how many subjects in each group
experienced a "durable recovery"—that is, eight consecutive
weeks of a nondepressed, reasonably happy mood. This outcome measure, Sachs
explained to Psychiatric News, "is a much more stringent
criterion than that used in prior studies, and we believe it represents a much
more clinically meaningful measure of outcome."
They found that durable-recovery evidence was about the same for both
groups—24 percent for the group getting an antidepressant and 27 percent
for the placebo group. Thus, "for the treatment of bipolar depression,
we found that mood-stabilizing monotherapy prov ides as much benefit as
treatment with mood stabilizers combined with a standard
antidepressant," the researchers concluded.
In the second investigation, Sachs and his group wanted to determine
whether intense psychotherapy could aid and hasten recovery from bipolar
depression. They selected 293 depressed bipolar patients to answer this
question and randomly divided them into two groups. They made sure that the
groups did not differ significantly at the time of randomization on
demographics, illness history, current clinical state, or types of medications
they were taking for their bipolar illness.
One group was assigned to a control condition called "collaborative
care." It consisted of three sessions over a six-week period to educate
subjects in the diagnosis, management, and treatment of bipolar disorder; the
importance of medication adherence; how mood states can bias thinking; how to
improve relationships; and other aspects of dealing with a bipolar
The other group was assigned to an experimental condition, which involved
up to 30 sessions of intense psychotherapy over nine months. It consisted of
an enhanced version of collaborative care plus cognitive-behavioral therapy
(CBT), an enhanced version of collaborative care plus family-focused therapy,
or an enhanced version of collaborative care plus interpersonal and
For example, individuals in the CBT arm worked on challenging negative
thoughts or dysfunctional beliefs. Those in the interpersonal and
social-rhythm therapy arm worked on resolving interpersonal problems and
stabilizing their times for eating, sleeping, and exercise in hopes that a
stable lifestyle would help stabilize their moods. And those in the
family-focused therapy arm, along with their relatives, were versed in how
stress can trigger manic or depressive episodes, how to communicate better
with each other, and how to develop a relapse-prevention plan.
Subjects' progress or lack of progress toward recovery was tracked from the
start of the study to 12 months later.
At the end of the year, 64 percent of subjects who had received intensive
psychotherapy were no longer depressed, whereas 52 percent of subjects who had
received the control condition were. This was a statisticaly significant
difference. Moreover, the average time to recovery among subjects in the
intensive psychotherapy group was 113 days, while it was 146 days among
subjects in the control group.
Furthermore, the researchers could find no significant differences among
the three intensive psychotherapies in their ability to aid and sustain
recovery from depression. The reason, they said, may be due to the fact that
their inquiry did not include enough subjects to detect such differences or
that the psychotherapies, which are similar in many ways, are truly comparable
Thus, "given the limited benefits of antidepressant medications in
patients with bipolar depression who are taking mood stabilizers," Sachs
and his team concluded in their Archives of General Psychiatry
report, "referral for intensive psychosocial treatment seems to be an
especially important addition to clinical care."
But how about cost? "Intensive treatments [such as these], although
seeming to be more effective than brief treatments in hastening recovery from
episodes, maintaining stability, and delaying recurrences, are also more
costly," Sachs and his group said. However, "treatment-associated
costs must be carefully balanced against the potential gains for patients in
functioning and quality of life and, possibly, reductions in rates of
hospitalization or polypharmacy."
Sachs told Psychiatric News that the most crucial take-home
messages from these two studies are that "it is not necessary to add a
standard antidepressant medication when starting treatment for patients with
bipolar depression [and that] the strongly positive outcomes for the
psychosocial interventions suggest that these treatments should always be
offered to bipolar depressed patients."
"Effectiveness of Adjunctive Antidepressant Treatment for
Bipolar Depression" can be accessed at<http://content/nejm.org>
by entering the title in the "Search NEJM" box. An abstract of"
Psychosocial Treatments for Bipolar Depression" is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/64/4/419>.▪