Study Finds Lithium Is Best Drug for Preventing Suicides
An inexpensive drug for bipolar disorder that has been shunted aside in favor of newer, more heavily marketed drugs is actually much more effective at preventing suicides and should be the drug of choice for first treatment of such patients, researchers report today.
Lithium is just as effective as the newer Depakote at preventing the wild mood swings associated with this widespread, disabling disorder, but patients who take Depakote are 2.7 times as likely to commit suicide as those who take lithium, the report says. That is a major difference, because suicide is 10 to 20 times more common among bipolar patients than in society at large.
“Psychiatry has never been able to say that what we do saves lives, which is the ultimate goal of medicine,” said Dr. Frederick Goodwin of the George Washington University Medical Center, who led the study of more than 20,000 patients. “With lithium, now we can.”
The new study, reported today in the Journal of the American Medical Assn., “makes an argument that lithium should be reconsidered as the first-line treatment [for bipolar disorder], which is probably where it should have been all along,” added Dr. Norman Sussman, a psychopharmacologist at New York University who was not involved in the study. “If we can reduce the risk of suicide, that is a good argument for using the drug.”
Bipolar disorder -- in which patients swing between deep depression and manic highs -- is one of the most common mental problems in the United States, affecting 1.3% to 1.5% of the population. As many as one in every five bipolar patients attempt suicide at some time in their lives.
Thirty years ago, there were no drugs to treat the disorder. Then researchers discovered that lithium smoothed the mood swings in as many as two-thirds of the patients. It was the first important drug for mental problems of any sort. But the drug could not be patented, so pharmaceutical companies couldn’t afford research and promotion. Nonetheless, lithium was widely used until Depakote -- generically known as divalproex -- became available in the early 1990s.
As recently as 1994, Goodwin said, lithium accounted for 80% of prescriptions for bipolar disorder. In 2001, divalproex accounted for more than 70%. Annual sales of lithium are now about $43 million per year, while those of Depakote are more than $1 billion, he said.
Many young psychiatrists, he noted, have not even received any training in using lithium. Some have been swayed by reports of excessive side effects associated with lithium, Goodwin added, but the two drugs actually have about the same risks.
Goodwin and his colleagues studied the records of 20,638 bipolar patients who were members of two HMOs, the Kaiser Permanente Medical Care Program in Oakland and the Group Health Cooperative in Seattle.
They did not consider the efficacy of the two drugs, but rather looked at deaths and hospital admissions resulting from suicide attempts. They found 31.3 suicide attempts per 1,000 people per year among those taking divalproex compared with 10.8 attempts among those taking lithium. There were 1.7 suicides per 1,000 people per year in the first group, compared with 0.7 in the second group.
Goodwin conceded that the team does not know why the rates were so much better for lithium users. Lithium is effective at reducing depression, and most suicide attempts occur during the depressive stages of bipolar disorder. But other effective antidepressants do not reduce suicide risk, so it is unlikely that that is the primary reason, he said.
Independent studies have also shown that lithium is good at reducing both impulsive and aggressive behavior. “Suicide is a very aggressive act,” Goodwin said, and it is also an impulsive one, so the answer might lie in that direction.
Neither Goodwin nor Sussman is advocating stopping the use of divalproex. “There is no single drug that is best for everyone,” Goodwin said. “Some patients respond better to one than to the other.”
In fact, the two drugs are often used now in combination, which may provide the reduced suicide risk of using lithium alone.
But no one knows. Because most patients in the study received only one or the other, there were not enough receiving both to reach any conclusions about the effect on suicides.
Goodwin also noted that there are newer drugs, such as lamotrigine (trade named Lamictal), that may be better than divalproex. But so far, there have been no studies on whether they reduce the risk of suicide.
