Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial.

Abstract

Importance:

Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression.

Objective:

To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event.

Design, Setting, and Participants:

This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019.

Interventions:

Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo.

Main Outcomes and Measures:

Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide.

Results:

The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group.

Conclusions and Relevance:

In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, 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.

Trial Registration:

ClinicalTrials.gov Identifier: NCT01928446.

• Authors: Ira R Katz, Malcolm P Rogers, Robert Lew, Soe Soe Thwin, Gheorghe Doros, Eileen Ahearn, Michael J Ostacher, Lynn E DeLisi, Eric G Smith, Robert J Ringer, Ryan Ferguson, Brian Hoffman, James S Kaufman, Julie M Paik, Chester H Conrad, Erika F Holmberg, Tamara Y Boney, Grant D Huang, Matthew H Liang, Li+ plus Investigators
• Journal: JAMA psychiatry (JAMA Psychiatry) Vol. 79 Issue 1 Pg. 24-32 (01 01 2022) ISSN: 2168-6238 [Electronic] United States
• PMID: 34787653 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antimanic Agents
• Antipsychotic Agents
• Lithium

Topics

• Adult
• Antimanic Agents (pharmacology, therapeutic use)
• Antipsychotic Agents (pharmacology, therapeutic use)
• Bipolar Disorder (complications, psychology)
• Depressive Disorder, Major (complications, psychology)
• Double-Blind Method
• Female
• Humans
• Lithium (pharmacology, standards, therapeutic use)
• Male
• Middle Aged
• Outcome Assessment, Health Care (methods, statistics & numerical data)
• Suicidal Ideation
• Suicide, Attempted (prevention & control, psychology, statistics & numerical data)
• Veterans (psychology, statistics & numerical data)