Decreased risk of suicides and attempts during long‐term lithium treatment: a meta‐analytic review
Open accessAbstract
Objectives: To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long‐term lithium treatment. Methods: Broad searching yielded 45 studies providing rates of suicidal acts during lithium treatment, including 34 also providing rates without lithium treatment. We scored study quality, tested between‐study variance, and examined suicidal rates on versus off lithium by meta‐analytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). Results: In 31 studies suitable for meta‐analysis, involving a total of 85,229 person‐years of risk‐exposure, the overall risk of suicides and attempts was five times less among lithium‐treated subjects than among those not treated with lithium (RR = 4.91, 95% CI 3.82–6.31, p < 0.0001). Similar effects were found with other meta‐analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser lithium superiority. Omitting one very large study or those involving lithium‐discontinuation had little effect on the results. The incidence‐ratio of attempts‐to‐suicides increased 2.5 times with lithium‐treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication‐year or study size. Conclusions: Risks of completed and attempted suicide were consistently lower, by approximately 80%, during treatment of bipolar and other major affective disorder patients with lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials.
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A meta-analysis of non-randomized studies suggested risk of attempts and suicide was 5 times less with lithium treatment.
“A meta-analysis of RCTs in bipolar disorder found no data on lithium’s effect on suicide prevention(81), however a meta-analysis of non-randomized studies suggested that risk of attempts and suicide was 5 times less with lithium treatment.(82)”
From Improving Suicide Prevention Through Evidence-Based Strategies: A Systematic Review (2021) · cites this paper as [82]
The Meta-analysis: all suicide acts section reports a 4.91-fold lower risk of suicide or attempts during lithium treatment, supporting the approximate five-fold figure. But that estimate pools 31 studies, including five RCTs, so describing it as a meta-analysis of non-randomized studies alone is inaccurate. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRisks for hospitalization, suicide, and lost productivity are increased with non-adherence or discontinuation.
“Risks for hospitalization, suicide, and lost productivity are also increased with non‐adherence or discontinuation.350, 351, 352”
From Canadian Network for Mood and Anxiety Treatments ( <scp>CANMAT</scp> ) and International Society for Bipolar Disorders ( <scp>ISBD</scp> ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [352]
The Subgroup comparisons and Discussion (pages not provided) associate lithium treatment and adherence with lower suicidal risk, although the comparison of suicide attempts before and after discontinuation offers only limited evidence of an additional post-discontinuation increase. The paper does not substantiate the attributed increases in hospitalization or lost productivity. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLithium is effective in preventing both manic and depressive episodes, with greater prophylactic efficacy against mania than depression.
“In general, lithium is the gold standard for maintenance treatment, as it is effective in preventing both manic and depressive episodes (magnitude of prophylactic efficacy greater against mania vs depression)”
From Canadian Network for Mood and Anxiety Treatments ( <scp>CANMAT</scp> ) and International Society for Bipolar Disorders ( <scp>ISBD</scp> ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [352]
The Discussion states that lithium has a substantial ability to limit recurrences of depressive illness in bipolar I and II disorder. It does not establish that lithium prevents manic episodes more effectively than depressive episodes, or describe it as the gold standard for maintenance treatment; the review’s main finding concerns suicide risk. (LLM, conf=0.82)
Experimental — accuracy not yet measuredLithium appears to have a degree of anti-suicidal effects.
“and appears to have a degree of anti‐suicidal effects.352, 369, 409, 410, 411, 412, 413”
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- Authors
- Baldessarini, R. J., Tondo, L., Davis, P., Pompili, M., Goodwin, F. K., & Hennen, J.
- Affiliations
- Harvard University (US)
- George Washington University (US)
- Corresponding author
- Baldessarini, Ross J
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2006-10
- Volume
- 8
- Issue
- 5p2
- Pages
- 625-639
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- OpenAlex
- W2124464240
- Cited by
- 753
- References
- 82
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 25 · 2023: 21 · 2022: 25 · 2021: 28 · 2020: 185 · 2019: 21 · 2018: 26 · 2017: 31 · 2016: 40 · 2015: 39 · 2014: 43 · 2013: 40 · 2012: 36
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Stanley Medical Research Institute
- National Alliance for Research on Schizophrenia and Depression
- Bruce J. Anderson Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- lithium, suicide, suicide attempts, bipolar disorder, major affective disorders, long-term lithium therapy, suicide risk reduction, lithium discontinuation, mood disorders
- MeSH terms
- Bipolar Disorder, Humans, Risk Factors, Suicide, Suicide, Attempted, Time Factors, Prevalence, Lithium Carbonate
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