CLEVELAND -- For the first time, researchers have demonstrated in separate short-term trials that a single drug therapy may be effective in treating both the manic and depressive phases of bipolar disorder. The condition (bipolar I and II) affects approximately 8 million Americans, who have relied on a combination of drugs to manage their symptoms, and who remain at high risk of committing suicide because of the difficulty in treating the disorder.
A study of the antipsychotic drug Seroquel is published in the July issue of the American Journal of Psychiatry. The study's principal investigator is Joseph R. Calabrese, MD, principal investigator and director of the National Institute of Mental Health (NIMH) Bipolar Research Center at University Hospitals of Cleveland and Case Western Reserve University School of Medicine.
Dr. Calabrese led the randomized trial of 542 patients with bipolar depression at 39 sites in the United States. Seroquel is currently approved for the short-term treatment of acute manic episodes in bipolar I disorder and the treatment of schizophrenia. This is the first study of Seroquel in patients with both bipolar I (defined as one fully manic episode with periods of major depression) and bipolar II (defined as periods of hypomania, or high levels of energy and impulsiveness alternating with episodes of major depression), in which researchers specifically studied the drug's impact on the depressive phase of the illness. Typically, antipsychotic medications are not used as specific treatments for bipolar depression.
"Though we will soon undertake an even larger trial, these preliminary findings should shape the standard of care for bipolar disorder going forward," says Dr. Calabrese, professor of psychiatry at Case and a nationally renowned researcher in bipolar disease. The Center, which he co-directs with pediatric psychiatrist Dr. Robert Findling, is the first NIMH-funded center exclusively dedicated to the development of new treatments for bipolar disorder.
"There was a dramatic response within eight days of beginning treatment in patients who were symptomatic with bipolar depression," says Dr. Calabrese. "About 50% of patients responded quickly to treatment with Seroquel versus placebo, achieving remission from their symptoms, with the response lasting through the eighth and last week of the trial. Seroquel was also twice as effective as placebo in decreasing suicidal thoughts associated with acute bipolar depression."
"Patients who respond most positively are probably those who also exhibit anxiety and agitation," adds Dr. Calabrese. "We are not certain as to the mechanism of action in the brain, however we know the drug impacts neurotransmitters dopamine and serotonin. The most common side effect is fatigue, so it may not be the best initial approach in patients who experience significant lethargy as a symptom of depression."
The trial tested two dose levels of Seroquel (quetiapine fumarate), 300 or 600mg/d, versus placebo. Of the 539 patients enrolled, 358 had bipolar I and 181 had bipolar II. Common side effects included dry mouth (43%), sedation (31%), sleepiness (26%), dizziness (20%) and constipation (11%). The research was supported by AstraZeneca Pharmaceuticals.
This study was first presented at the 2004 annual meeting of the American Psychiatric Association.
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