Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder
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, Deepika Agrawal, Naheed Akhtar, Maria Androsenko, Bert Berger, Venkatesh Bhat, Lisa Brenner, Lokaranjit Chalasani, Dennis Chang, Peijun (P.J.) Chen, Brandon Cornejo, David Cory, Dena Davidson, Patrica Dickmann, Erica Duncan, Ronald Fernando, Karen C. Floyd, Steven Forman, Phillip Gale, Jayant Geete, Michael Ignatowski, Kari Jones, Timothy Juergens, George Jurjus, Gauri Khatkhate, Eric P. Konicki, Dean Krahn, Gunnar Larson, Susan Leckband, Joel Mack, Scott Matthews, Lorna Mayo, Erin McGlade, James Michalets, Elizabeth Miller, Emil Muly, Alexander Niculescu, Michael Ostacher, Prasad Padala, Kalpana Padala, Peggy Pazzaglia, Murray Raskind, Perry Renshaw, Geetha Shivakumar, Julia C. Smith, Dennis Sullivan, Patricia Suppes, Alan Swann, Lia Thomas, Shabnam Thompson, Erick Turner, Maria Umbert, Joseph Westermeyer, Amanda Wood, Hal Wortzel, Deborah Yurgelun-Todd
Journal: JAMA Psychiatry (2021)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. <h3>Main Outcomes and Measures</h3> Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. <h3>Results</h3> 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. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01928446