Lithium Often Takes Backseat To Other Bipolar Therapies

Patients with bipolar disorder who exhibit suicidal ideation are more likely to be prescribed antidepressants and second-generation antipsychotics (SGA) than lithium, despite lithium's reputation for an antisuicide effect.

Data published in the December 2005 Psychiatric Services by the team running the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) indicates that lithium appears to be “reserved for those patients with more severe illness characteristics.” The report provides a snapshot of current medications taken by the first 1,000 patients who entered the STEP-BD study, which was funded by the National Institute of Mental Health (NIMH).

For many years lithium has been thought to exert an antisuicide effect, with some researchers reporting that in patients with bipolar disorder, lithium is associated with up to a six-to eightfold reduction in the risk of suicide attempt or completion compared with placebo. Other researchers reported that suicide completion was 2.7 times more likely to occur in patients with bipolar disorder on divalproex compared with those on lithium.

Yet these earlier studies did not control for other medications taken concomitantly or for severity of illness at baseline relative to prescription choice. In addition, “little is known about the antisuicidal benefits of other new agents for bipolar disorder, particularly the second-generation antipsychotics.”

STEP-BD investigators, led by Gary Sachs, M.D., a professor of psychiatry at Massachusetts General Hospital and Harvard University, enrolled nearly 5,000 patients aged 15 and older with bipolar disorder I, II, or NOS, or cyclothymia, at 11 academic research centers across the U.S. The researchers' goal of the current report was to provide “a description of community-based pharmacotherapy treatments relative to suicidal ideation” in the first 1,000 patients to enter the study. The study group was assessed between November 1999 and April 2001 to determine“ prevalence of prescriptions for mood stabilizers, second-generation antipsychotics, and antidepressants and the clinical features of patients who received these different classes of medications.”

A battery of assessments was administered to each patient, yielding demographic details, past and current signs and symptoms of mental illness, and past and current treatments.

At baseline, 605 of 998 patients were euthymic (61 percent), 58 (6 percent) were manic or hypomanic, 87 (9 percent) were mixed or cycling, and 248 (25 percent) were depressed (two patients did not complete the entire baseline assessment).

Among the 998 patients, 211 (21 percent) exhibited signs of suicidal ideation. Suicidal ideation was significantly more common among persons who were experiencing depressive (49 percent) or mixed episodes (47 percent) than those who were manic or hypomanic (9 percent) or euthymic (7 percent).

Sachs and his coauthors reported that 362 (36 percent) patients were taking lithium at baseline, and 349 (35 percent) were taking divalproex. Of the 270 patients (27 percent) who were taking an antipsychotic, nearly all (264) were taking an SGA. Of those taking an SGA, about two-thirds were also taking either lithium or divalproex.

The number of patients taking an antidepressant was 418 (42 percent); 346 (83 percent) were taking one antidepressant, while 72 (17 percent) were taking at least two antidepressants at the beginning of the study.

Finally, Sachs and his colleagues reported that “rates of suicidal ideation were similar between patients who were taking any lithium and those who were not. Rates of suicidal ideation were also not statistically significantly different between those taking divalproex and those who didn't take divalproex. However, the mean number of prescribed medicines for patients with suicidal thoughts was higher than for those without suicidal thoughts.

“Our findings suggest,” Sachs and his colleagues wrote,“ that after use of other medications and baseline severity indices were controlled for (such as severity of illness and history of suicide attempts), psychiatrists may be more likely to prescribe lithium for suicidal patients with bipolar disorder.”

“Suicidal Ideation and Pharmacotherapy Among STEP-BD Patients” is posted at<http://ps.psychiatryonline.org/cgi/content/full/56/12/1534>.▪

Psychiatr Serv 2005 56 1534