Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study
Open accessAbstract
Background: Lithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer. Aims: To investigate the association between lithium and cancer risk in patients with bipolar disorder. Method: A retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer. Results: Compared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554–0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516–1.125), 0.919 (95% CI 0.640–1.318) and 0.552 (95% CI 0.367–0.831), respectively. Conclusions: Lithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose–response relationship for cancer risk reduction was observed.
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In a Taiwanese population-based retrospective cohort of 1 million people, lithium treatment for BD was associated with reduced risk of both stroke and cancer compared to propensity-matched controls.
“Two studies from a random sample of 1 million people, taken from a large population‐based retrospective cohort in Taiwan, demonstrated a reduced risk of both stroke and cancer associated with lithium treatment for BD. The lithium group was compared with propensity‐matched controls.”
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 [795]
The Data sources section describes a retrospective cohort drawn from a random sample of 1 million people in Taiwan, and Main findings reports lower overall cancer risk among lithium users with bipolar disorder. This paper does not report a lithium–stroke risk finding: it mentions stroke only in connection with validation of the database. The Statistical analysis section describes propensity-score weighting, not propensity matching, of the comparison groups. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn a sample of 4729 patients diagnosed with BD, lithium exposure was associated with a reduced risk of cancer compared to a group prescribed anticonvulsant medications (HR = 0.735, 95% CI 0.55-0.97).
“In the second study, in a sample of 4729 patients diagnosed with BD, lithium exposure was associated with a reduced risk of cancer, compared to a group prescribed anticonvulsant medications. (Lithium with or without anticonvulsant HR = 0.735, 95% CI 0.55‐0.97).”
The second study demonstrated a dose-response relationship between lithium and cancer risk.
“The study also demonstrated a dose‐response relationship.795”
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- Authors
- Huang, R.-Y., Hsieh, K.-P., Huang, W.-W., & Yang, Y.-H.
- Affiliations
- Kaohsiung Medical University (TW)
- Corresponding author
- Yang, Yi-Hsin
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2016-11
- Volume
- 209
- Issue
- 5
- Pages
- 393-399
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2465989363
- Cited by
- 83
- References
- 28
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 5 · 2020: 11 · 2019: 7 · 2018: 11 · 2017: 10 · 2016: 3
- FWCI
- 9.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- lithium, bipolar disorder, cancer risk, glycogen synthase kinase-3 inhibition, antiepileptic drugs, dose-response relationship, defined daily doses
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Anticonvulsants, Bipolar Disorder, Female, Humans, Male, Middle Aged, Neoplasms, Registries, Retrospective Studies, Risk, Taiwan, Lithium Compounds, Antimanic Agents, Young Adult
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