The largest trial of lithium to prevent repeat suicide attempts was stopped early: no difference from placebo
A VA trial randomised 519 veterans who had survived a recent suicide-related event to lithium or placebo on top of usual care. It was stopped for futility: 65 events on lithium, 62 on placebo (hazard ratio 1.10).
Well-supported by good-quality research. how we score evidence
Caveat on this rating: One trial in veterans (84% men) who had already attempted, with modest lithium levels and a broad composite outcome; deaths were too few to compare. It tests adding lithium to usual care, not lithium started as the main treatment. The older meta-analysis of 48 smaller trials points the other way.
The trial the lithium and suicide meta-analyses were waiting for, and what it found.
Significant findings
Katz and colleagues ran a double-blind, placebo-controlled trial at 29 Veterans Affairs medical centres (VA Cooperative Studies Program #590). Everyone enrolled had bipolar disorder or depression and had survived a suicide attempt, an interrupted attempt or a hospital stay to prevent suicide in the past six months. They got extended-release lithium, starting at 600 mg a day, or placebo, added to their usual VA care.
"The trial was stopped for futility after 519 veterans" were randomised: 255 to lithium, 264 to placebo. There was "no overall difference in repeated suicide-related events" (hazard ratio 1.10; 95% CI 0.77 to 1.55). In all, 127 people (24.5%) had an event: 65 on lithium and 62 on placebo. One person died in the lithium group and three in the placebo group. No unexpected safety problems were seen.
The authors conclude that "simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events" in people already being treated for mood disorders with substantial other illness.
The other direction
This does not erase the older evidence. The 2013 meta-analysis (Cipriani, BMJ) found fewer suicides on lithium than placebo across 48 smaller trials, and observational studies point the same way; both are in this library. The VA trial asked a narrower question: does adding lithium to current care, in people who already attempted, cut repeat events of any kind? Its lithium levels were modest (mean 0.54 mEq/L in bipolar disorder and 0.46 in depression at three months), 84% of participants were men, and it measured a broad outcome, not deaths alone. Deaths were too few to compare. So the two can both be true: lithium may lower suicide in some groups, and still not help much when added this way.
What this does not show
It does not say whether any one person should start, keep or stop lithium. That is a decision to make with a prescriber.
Worth asking
If lithium was suggested for me partly for suicide prevention, what does the evidence show for someone in my situation, and what else is part of the safety plan?
Source
Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial — Katz IR, Rogers MP, Lew R, Thwin SS, Doros G, Ahearn E, Ostacher MJ, DeLisi LE, Smith EG, Ringer RJ, Ferguson R, Hoffman B, Kaufman JS, Paik JM, Conrad CH, Holmberg EF, Boney TY, Huang GD, Liang MH (2022)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1001/jamapsychiatry.2021.3170
DOI: 10.1001/jamapsychiatry.2021.3170
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 519
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published October 2, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "strong evidence". Well-supported by good-quality research. It scores 80 out of 100 on our published rubric. One caveat travels with that badge: One trial in veterans (84% men) who had already attempted, with modest lithium levels and a broad composite outcome; deaths were too few to compare. It tests adding lithium to usual care, not lithium started as the main treatment. The older meta-analysis of 48 smaller trials points the other way. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial — Katz IR, Rogers MP, Lew R, Thwin SS, Doros G, Ahearn E, Ostacher MJ, DeLisi LE, Smith EG, Ringer RJ, Ferguson R, Hoffman B, Kaufman JS, Paik JM, Conrad CH, Holmberg EF, Boney TY, Huang GD, Liang MH (2022). Published in: Top-tier peer-reviewed journal. DOI: 10.1001/jamapsychiatry.2021.3170. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Independently funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.