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Research presented at a February conference sponsored by the American Foundation for Suicide Prevention (AFSP) shows that lithium reduces the risk of recurrent depression and can prevent suicidal behavior. The conference was funded by an unrestricted educational grant from Solvay Pharmaceuticals, the maker of Lithobid.
Conference participant and psychiatric researcher Frederick Goodwin, M.D., later told Psychiatric News, "The research is relevant because we now know that lithium has a significant impact on the death rate of bipolar patients. It is also timely because some are suggesting that the anticonvulsant valproate is superior to lithium in the treatment of manic depression."
Goodwin is a research professor of pharmacology in the department of psychiatry and director of the Center on Neurscience, Medical Progress, and Society at George Washington University.
"In my opinion, it is premature to replace lithium as a first-line treatment because of its proven track record as a long-term maintenance treatment and its ability to prevent suicidal behavior," said Goodwin, a former director of the National Institute of Mental Health.
He referred to an extensive literature review published in the December 1997 Annals of the New York Academy of Sciences, suggesting that lithium patients with severe mood disorders, including bipolar and recurrent unipolar major depression, had on average a suicide rate six times less than that of similar patients not on lithium.
Goodwin also mentioned that one of the studies, published in the 1996 book In Lithium: Biochemical and Clinical Advances, in which 284 bipolar patients were treated with lithium showed a sixfold decrease in the risk of suicidal acts. After lithium was discontinued, there was a sevenfold increase in suicidal acts and a ninefold increase in fatalities.
"Any other single treatment in medicine that showed a similar sixfold treatment difference would be considered front-page news," said Goodwin.
Moreover, lithium was superior to the anticonvulsant carbamazepine in preventing suicides in a critical study published in a 1996 issue of Pharmacopsychiatry said Goodwin.
The results over a two-and-a-half-year follow-up show that patients with major affective disorders given lithium had no completed suicides compared with four or five completed suicides for patients given carbamazepine. However, the researchers noted that patients given carbamazepine were not withdrawn from lithium.
Goodwin also commented "that the one well-controlled study comparing lithium with valproate is difficult to interpret because neither drug was significantly superior to placebo in the main outcome variable, which was time to next episode."
However, according to that study's co-investigator, Robert Hirschfeld, M.D., "Emerging evidence suggests that valproate is superior to lithium because it is safer and has a more benign side-effect profile and more antidepressant properties."
The controlled, randomized study compared lithium with valproate and placebo in 372 patients with mild manic depression.
Hirschfeld, who is president of the AFSP and a member of APA's Council on Research, told Psychiatric News that the study has been submitted for publication.
Investigator Charles Bowden, M.D., also told Psychiatric News, "The results suggest that valproate is as effective if not somewhat more effective than lithium in preventing suicidal behavior, though the difference is not statistically significant."
Bowden is a professor of psychiatry at the University of Texas Health Science Center in San Antonio. He is also APA's Area 5 trustee and a Board liaison to APA's Council on Research.
Fifty percent of the patients in the multi-site trial were given valproate, 25 percent lithium, and 25 percent placebo during a one-year period.
Bowden explained, "Because of the large number of patients given placebo, for ethical and practical reasons we could not use more severely ill patients."
The results showed that no completed suicides occurred during the study. Patients treated with lithium had two suicide attempts compared with one for patients treated with valproate.Valproate showed a slight advantage over lithium in preventing suicidal ideation, said Bowden.
He commented that the main purpose of the study, funded by Abbott Laboratories, the maker of valproate, was to compare the drugs' efficacy in preventing recurrent episodes of manic depression. Bowden said the results did not show a significant difference between the two drugs in preventing mania relapses. This could be due to the less severe patient population and the high amount of educational support patients received.
Hirschfeld, who also chaired APA's work group on bipolar disorder, which developed the treatment practice guideline, agreed with Goodwin that patients doing well on lithium should not be switched to valproate and vice versa.
Goodwin added a caveat, "If a patient on valproate is highly suicidal, you might want a regimen that includes lithium. It is now common for clinicians to use more than one agent to stabilize a bipolar patient and enhance [the patient's] response."