Lithium may not reduce suicide-related events in veterans with mood disorders

Adding lithium to usual care for veterans with major depression or bipolar disorders did not reduce incidence of suicide-related events, according to results of a randomized clinical trial published in JAMA Psychiatry.

“Numerous observational studies suggest that lithium may prevent suicide and suicide attempts in patients with bipolar disorder or depression, with some studies suggesting that this may be somewhat independent of lithium’s effects on mood,” Ira R. Katz, MD, PhD, of the department of psychiatry at the Michael J. Crescenz Veterans Affairs (VA) Medical Center in Pennsylvania, and colleagues wrote. “However, these observations could reflect practitioners’ propensity for prescribing lithium to patients less prone to suicide attempts. A cohort study of veterans using propensity score matching found no difference in suicide rates for patients with bipolar disorder taking lithium vs. valproate.”

They noted that randomized clinical trials assessing whether lithium can prevent suicidal behavior among these patients have been underpowered.

In the current trial, Katz and colleagues sought to determine whether adding lithium to usual care would reduce the rate of repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide and deaths from suicide among veterans with bipolar disorder or depression who survived a recent event. They included veterans from 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission for suicide prevention within 6 months. Screening occurred between July 1, 2015, and March 31, 2019.

The researchers randomly assigned 255 participants to extended-release lithium carbonate starting at 600 mg per day and 264 participants to placebo. Participants had a mean age of 42.8 years and 82.4% were men. Main outcomes and measures included time to the first repeated suicide-related event and deaths from suicide.

Patients with bipolar disorder and patients with major depressive disorder had mean lithium concentrations at 3 months of 0.54 mEq per liter and 0.46 mEq per liter, respectively. Katz and colleagues found no overall difference in repeated suicide-related events between treatments (HR = 1.1; 95% CI, 0.77-1.55), nor did they observe unanticipated safety concerns. Suicide-related outcomes occurred among 127 (24.5%) participants, with 65 in the lithium group and 62 in the placebo group. The researchers reported one death in the lithium group and three in the placebo group.

“Simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities,” Katz and colleagues wrote.

In a related editorial, Ross J. Baldessarini, MD, and Leonardo Tondo, MS, MD, both of the department of psychiatry at Harvard Medical School in Boston, suggested using caution when interpreting these results.

“The new trial did not find evidence of an antisuicidal effect of adding lithium to complex treatment regimens in relatively small numbers of mostly male veterans with complex, although realistic, psychopathological conditions, given relatively brief treatment with low circulating levels of lithium,” they wrote. “Thus, its findings cannot be taken as evidence that lithium lacks antisuicidal effects. An ironic final note is that recruiting participants to such trials may be made difficult by an evidently prevalent belief that the question of antisuicidal effects of lithium is already settled, which it certainly is not.”