Suicidal Behavior During Lithium and Valproate Treatment: A Within-Individual 8-Year Prospective Study of 50,000 Patients With Bipolar Disorder
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OBJECTIVE: Conclusions regarding lithium's antisuicidal effect for bipolar disorder have been limited due to nonrepresentative subjects and potential confounding factors, including varying severity of illness. Findings regarding the effect of valproate, the most common alternative to lithium, are inconsistent for suicidal behavior. This study investigated the associations of these two drugs with the risk of suicide-related events, and possible differences between drugs, by using within-individual designs in a register-based longitudinal cohort. METHOD: Through linkage of multiple Swedish national registers, 51,535 individuals with bipolar disorder were followed from 2005 to 2013 for treatment with lithium and valproate. Stratified Cox regression was used to estimate the hazard ratios of suicide-related events during treated periods compared with untreated periods. For significant associations between medication and suicide-related events, the population attributable fraction was estimated to assess the public health impact for patients with bipolar disorder. RESULTS: During follow-up, 10,648 suicide-related events occurred. The incidence rate was significantly decreased by 14% during lithium treatment (hazard ratio 0.86, 95% confidence interval [CI] 0.78-0.95) but not during valproate treatment (hazard ratio 1.02, 95% CI 0.89-1.15). The difference in hazard ratios of suicide-related events between lithium and valproate was statistically significant. Estimates of the population attributable fraction suggested that 12% (95% CI 4%-20%) of suicide-related events could have been avoided if patients had taken lithium during the entire follow-up. CONCLUSIONS: The results suggest that lithium should be considered for patients with bipolar disorder with suspected suicidal intentions, although risk for suicide is only one of the considerations when providing clinical care.
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Within-individual designs have shown a 14% decrease in incidence of suicidal acts and completed suicide among people treated with lithium for bipolar disorder.
“Specific pharmacoepidemiologic approaches, called “within-individual designs,” that account for factors that remain stable in an individual patient (e.g., background genetic risk and environmental adversities) have shown a 14% decrease in the incidence of suicidal acts and completed suicide among people treated with lithium for bipolar disorder65”
From Suicide (2020) · cites this paper as [65]
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- Authors
- Song, J., Sjölander, A., Joas, E., Bergen, S. E., Runeson, B., Larsson, H., Landén, M., & Lichtenstein, P.
- Affiliations
- Broad Institute (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2017-08-01
- Volume
- 174
- Issue
- 8
- Pages
- 795-802
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2622459767
- Cited by
- 147
- References
- 36
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 17 · 2023: 14 · 2022: 18 · 2021: 19 · 2020: 20 · 2019: 14 · 2018: 17 · 2017: 3
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- 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
- bipolar disorder, lithium, valproic acid, suicidal behavior, suicide risk, antisuicidal effects, mood stabilizers, population attributable fraction, suicide prevention
- MeSH terms
- Suicide Prevention, Adolescent, Adult, Aged, Bipolar Disorder, Female, Humans, Longitudinal Studies, Male, Middle Aged, Registries, Risk, Suicide, Suicide, Attempted, Sulfates, Sweden, Valproic Acid, Proportional Hazards Models, Information Storage and Retrieval, Lithium Compounds, Antimanic Agents, Young Adult
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