Sept. 16, 2003 -- The most widely prescribed mood stabilizer for bipolar disorder in the U.S. is not as effective as lithium for reducing the risk of suicide, new research suggests.
In a study that included more than 20,000 bipolar disorder patients, those taking the drug Depakote had a suicide rate almost three times higher than those taking lithium. The findings are reported in the Sept. 17 issue of TheJournal of the American Medical Association.
After adjusting for other factors that could play a role in suicide, such as other medical or psychiatric conditions, the researchers also found that the risk of suicide attempts resulting in hospitalization was 70% higher for patients taking Depakote.
All but Abandoned
Lead researcher Frederick K. Goodwin, MD, says the findings should serve as a wake-up call to many psychiatrists who have all but abandoned lithium for bipolar disorder in favor of newer medications, which are heavily marketed by their manufacturers. He adds that this is especially true of younger doctors, who are often not taught about lithium in medical school.
"Lithium is the number one mood stabilizer in every country except America," he tells WebMD. "If it is really better for some patients, then we really should be rethinking this rush away from it. At the very least we need to make sure that nobody gets out of residency in this country without knowing how to use it."
Roughly 1.5% of the U.S. population suffers from bipolar disorder, which was once known as manic depression. Characterized by extreme mood swings with episodes of severe depression, people with bipolar disorder are 10 to 20 times more likely to commit suicide than the general population.
The introduction of lithium in the 1970s revolutionized the treatment of bipolar disorder and gave psychiatrists their first effective drug for preventing suicide, Goodwin says. Due to their ability to help stabilize mood, Depakote and several other antiseizure drugs have been used since the mid-1990s to treat patients with bipolar disorder.
This study is the first to compare lithium to Depakote for the prevention of suicide. The 20,000-plus patients with diagnoses of bipolar disorder were followed over the course of the seven-year study.
After adjusting for other suicide risk factors, the researchers concluded that the risk of suicide and suicide attempts was 1.5 to 3 times greater during treatment with Depakote than with lithium. The findings bolster those of a European study concluding that lithium is better for suicide prevention than another antiseizure drug used to treat bipolar disorder, known as Tegretol.
Antiseizure Drugs Better for Some
Though he says that lithium is underused in the treatment of bipolar disorder, Goodwin says the antiseizure drugs, either alone or in combination with lithium, represent a better choice for many patients. Patients who are sicker, he says, and those who also have substance abuse problems tend to respond better to the newer drugs.
In an editorial accompanying the study, Ross J. Baldessarini, MD, and Leonardo Tondo, MD, of Harvard Medical School write that preventing suicides among patients with bipolar disorder and other mental illnesses has been too long neglected as a sign of treatment success. The two recently published a review showing that untreated bipolar patients were almost nine times more likely to commit suicide than patients taking lithium long term.
"Not until this year has the FDA approved any treatment to prevent suicidal behavior -- with the recent approval of [Clozaril] for such purposes among patients with schizophrenia or schizoaffective disorder," the two write. "This approval was supported by a prospective randomized study showing about 32% lower risk of non-lethal suicidal behaviors ... Hopefully, such renewed interest in the potentially treatment-modifiable lethality of major mental disorders will be sustained and increasingly successful."