Lithium Did Not Reduce Suicide-Related Events Among Veterans With a History of Suicidality

Lithium added to usual care did not decrease suicide-related events among veterans with major depression or bipolar disorder. These findings were published in JAMA Psychiatry.

Veterans (N=519) who had an inpatient admission to prevent suicide within 6 months or who had an episode of suicidal behavior at 29 Veterans Affairs (VA) medical centers between 2015 and 2019 were recruited for this study. Patients were stratified by condition (depression or bipolar disorder) and suicide history (prior attempt or no prior attempt) and randomized to receive 600 mg/d extended-release lithium carbonate (n=255) or placebo (n=264) in addition to usual care. The lithium dose was titrated upward until steady state lithium reached a concentration of 0.6-0.8 mEq/L. The veterans were assessed for time to first episode of a suicide-related event.

The patients were aged mean 42.8 (range, 20-72) years, 84.2% were men, 84.6% had major depressive disorder, 15.4% had bipolar disorder, 59.7% had posttraumatic stress disorder, 8.9% had panic disorder, 72.6% were White, 41.6% were divorced, 86.7% were heterosexual, and 45.3% had some college credit but no degree.

The treatment exposure was longer for patients with major depression than for bipolar disorder (mean, 6.7 vs 5.6 months). All participants attended an average of 1.15 mental health service visits per month.

During the study period, there were 197 suicide-related events among 127 participants. Events included hospitalization to prevent suicide (n=73), interrupted suicide attempt (n=28), suicide attempt (n=21), and other (n=4).

Events occurred among 25.5% of the lithium recipients compared with 23.5% of the placebo group (hazard ratio [HR], 1.10; 95% CI, 0.77-1.55; P =.61).

Participants who stopped their allocated treatment during the study were at increased risk for a suicide-related event (HR, 2.86; 95% CI, 1.48-5.53; P =.007). Stratified by study drug, no group difference for this effect was observed (HR, 1.11; 95% CI, 0.78-1.57; P =.55).

The most common serious adverse event was hospitalization to prevent suicide. Discontinuation due to serious adverse event occurred among 7 participants and 1 developed lithium toxic effects.

There were 4 deaths during the study duration (lithium: n=1; placebo: n=3). The deaths were due to self-inflicted gunshot (n=2); opioid overdose (n=1); and death by hanging, strangulation, or suffocation (n=1).

These findings may not be generalizable to non-VA health care settings.

This study did not find evidence that lithium was an effective treatment strategy for preventing suicidality.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.