Ineffective Antidepressants 2007-03-29 Global ++Antidepressants Don’t Help Bipolar Patients: New England Journal of Medicine

First paragraph reads:  "Antidepressants, which are widely prescribed with mood stabilizers to treat
patients with bipolar disorder, do not work in relieving the depressive symptoms of the illness, a large federal study reported Wednesday.",1,3436

THE Los Angeles Times

Antidepressants Don't Help Bipolar Patients, Study Finds
Combined With A Mood Stabilizer, As Many Doctors Prescribe, The Drugs Are
Found To Have No Effect On Depressive Symptoms.

By Denise Gellene
 March 29, 2007 

Antidepressants, which are widely prescribed with mood stabilizers to treat
patients with bipolar disorder, do not work in relieving the depressive
symptoms of the illness, a large federal study reported Wednesday.

The study in the New England Journal of Medicine narrows the already limited
number of treatments for bipolar disorder, which affects 5.7 million adults
in the U.S., experts said.

"A new generation of drugs is needed," said Dr. Thomas R. Insel, director of
the National Institute of Mental Health. "It is clear from this data that
antidepressants are not the answer."

Still, some doctors said antidepressants would continue to have a role
because there were so few options, and the drugs seemed to alleviate other
symptoms that often accompanied the complex disorder.

"Many people we see are refractory to a mood stabilizer alone, and adding an
antidepressant markedly improves them," said Dr. Lori Altshuler, professor
of psychiatry at UCLA, who was not involved in the study.

But Altshuler, who has consulted for companies that market drugs for
psychological disorders, said the study clearly demonstrated that patients
should first try a mood stabilizer, which could also have antidepressant

People with bipolar disorder experience severe mood swings between
depression and mania, a state marked by an excess of energy and
restlessness. For most patients, depressive episodes are three times more
common and longer-lasting than those of mania. Symptoms of the disorder can
interfere with daily activities, and severe cases carry a risk of suicide.

Standard treatment consists of mood stabilizers such as lithium, valproate
and carbamazepine. Antidepressants are often added to control severe
depressive swings, despite concerns the drugs may trigger a switch to a
manic episode.

Researchers estimated that 50% to 70% of people with bipolar disorder take
antidepressants, although the Food and Drug Administration has approved none
of the drugs as a treatment for the disorder.

The study, part of the institute's $27-million Systematic Treatment
Enhancement Program for Bipolar Disorder, set out to determine whether the
common antidepressants Wellbutrin and Paxil would enhance the benefits of
mood-stabilizer drugs. The study was also designed to find out whether the
antidepressants would trigger mania.

Previous studies provided mixed results on effectiveness. Wellbutrin and
Paxil were chosen because earlier studies indicated they were less likely to
trigger mania than other antidepressants.

In the study, 366 patients at 22 academic centers in the U.S. were randomly
assigned to receive one of the two antidepressants or a placebo for 26
weeks, in addition to their mood stabilizers. Patients also received
psychological and social therapy.

The study, designed to mimic real-world conditions, differed from a typical
clinical trial in that many patients had complicating disorders, including
anxiety, substance abuse or psychosis.

Of the 179 participants who received an antidepressant in addition to a mood
stabilizer, 23.5% achieved a durable recovery, defined as an eight-week
period marked by no more than two depressive or two manic symptoms.

In the placebo group, 27.3% of patients achieved a durable recovery.

The difference between the groups was not statistically significant,
researchers said. 

The criteria of durable recovery were stricter than in other trials, which
used rating systems to measure overall improvements in patients' moods.

Researchers reported there was no sign that Wellbutrin or Paxil could
trigger a manic episode. They said 10.1% of patients on antidepressants and
10.7% of those on placebo exhibited manic symptoms.

Lead author Dr. Gary Sachs, director of the bipolar clinic at Massachusetts
General Hospital, said the study should guide the way new patients were
treated, but there was no need for patients doing well on antidepressants to
quit taking them.

"There is no benefit from standard antidepressant medication," he said. "But
there is no risk to adding it, either."

In an editorial accompanying the report, Dr. Robert H. Belmaker of Ben
Gurion University in Beersheba, Israel, said the study would not settle
debates about the safety and efficacy of antidepressants in treatment of
bipolar disorder.

Patients who had become manic in response to antidepressants in the past
would not have enrolled in the trial, he said, casting doubt on whether the
drugs are safe for all bipolar patients.

Belmaker noted that two European reviews of published studies found
antidepressants to be effective, and that in his own practice he prescribed
antidepressants to patients with severe depression but mild mania. He said
that bipolar disorder showed wide variability in symptoms, which argued for
flexibility in treatment.