|Study Sheds Light on Medication Treatment Options
for Bipolar Disorder
For depressed people with bipolar disorder who are taking a mood
stabilizer, adding an antidepressant medication is no more effective
than a placebo (sugar pill), according to results published online
on March 28, 2007 in the New England Journal of Medicine.
The results are part of the large-scale, multi-site Systematic
Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a
$26.8 million clinical trial funded by the National Institutes
of Health’s National Institute of Mental Health (NIMH).
Bipolar disorder (http://www.nimh.nih.gov/healthinformation/bipolarmenu.cfm),
a sometimes debilitating illness marked by severe mood swings between
depression and mania, is usually treated with mood stabilizers
such as lithium, valproate, carbamazepine or other medications
that reduce mania. However, depression is more common than mania
in bipolar disorder, and depressive episodes tend to last longer
than episodes of mania. Antidepressant medications are often used
in addition to a mood stabilizer for treating bipolar depression,
but they are thought to confer a serious risk of a switch from
a depressive episode to a manic episode.
Finding the right treatment balance for people with bipolar disorder
is a constant challenge; STEP-BD aims to identify the best treatment
options. “Treating depression in people with bipolar disorder is
notoriously difficult,” said NIMH Director Thomas R. Insel. “STEP-BD
sought to determine if adding an antidepressant to a mood stabilizer
is effective and safe in treating depressive episodes. The results
suggest that antidepressants are safe but not more effective than
placebo as assessed in a large number of people with bipolar disorder.”
Lead author Gary Sachs, M.D., of Massachusetts General Hospital
and colleagues studied 366 participants at 22 sites across the
country. Unlike most clinical studies, participants were recruited
from clinical settings and were included in the study even if they
were being treated for co-existing disorders such as substance
abuse, anxiety or psychotic symptoms. Such open recruitment criteria
allows the study’s results to have broader applicability than a
tightly controlled trial in which people are excluded from participating
if they have co-existing disorders.
Before participants were randomized to one of two antidepressants — bupropion
(Wellbutrin) or paroxetine (Paxil) — or to a placebo, doctors
trained in the treatment of bipolar disorder adjusted participants’ mood
stabilizer doses to optimal levels, ensuring that they were receiving
the most appropriate amount.
After about 26 weeks, Sachs and colleagues found that 24 percent
of those who had been randomized to the antidepressants stayed
well for at least eight consecutive weeks — the study’s stringent
standard for recovery; 27 percent of those randomized to a placebo
stayed well long enough to meet the eight-week recovery standard,
indicating no difference between adding an antidepressant or adding
placebo. In addition, about 10 percent of each group experienced
emerging symptoms of mania, indicating that the antidepressants
did not trigger a manic switch any more than placebo. Finally,
when comparing the two antidepressants to each other, both showed
similar rates of response and manic switch.
“Results of STEP-BD indicate that careful management of mood stabilizer
medications is a reasonable alternative to adding an antidepressant
medication for treating bipolar depression,” said Dr. Sachs.
Future STEP-BD results will shed light on other treatment options
for bipolar disorder, including psychotherapeutic treatments.
The National Institute of Mental Health (NIMH) mission is to reduce
the burden of mental and behavioral disorders through research
on mind, brain, and behavior. More information is available at
the NIMH website, http://www.nimh.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.