It’s not just suicide — mood stabilizers protect against dying from medical illness, especially lithium
STUDY: Chen P-H et al, Acta Psychiatr Scand 2023;147:234–247, PMID: 36480299
STUDY TYPE: Nationwide cohort study
EVIDENCE GRADE: Low (4/10)
FUNDING: Ministry of Science and Technology, Taiwan; Taipei City Hospital
Background
People with bipolar disorder die at more than five times the expected rate — from suicide, yes, but also from heart disease, metabolic illness, and other natural causes. This study asked whether mood stabilizers (lithium and anticonvulsants) reduce not just suicide risk but natural-cause mortality as well.
The Study
Using Taiwan’s national health insurance database, researchers followed 25,787 hospitalized patients with bipolar disorder from 2001 to 2016, tracking 4,000 deaths. Mood stabilizer exposure was updated every 30 days to capture real-world prescribing patterns. Lithium, valproic acid, lamotrigine, and carbamazepine were analyzed separately.
Mood stabilizers as a class were associated with meaningfully lower risks of all-cause mortality (aHR = 0.58), suicide (aHR = 0.60), and natural mortality (aHR = 0.55) over the first five years after hospitalization. Lithium had the strongest effect across all three outcomes — cutting all-cause mortality nearly in half (aHR = 0.38) and suicide risk by 61% (aHR = 0.39). Valproic acid showed similar but smaller benefits. Lamotrigine and carbamazepine showed no significant association with mortality.
The protective effects of lithium were dose-dependent: more days on lithium, lower mortality. Earlier studies find similar benefits with lithium, including protective effects against stroke, cancer, osteoporosis, dementia, aging, and all-cause mortality.
Although antipsychotics were not included here, other studies have looked at them in mood disorders, finding either no change in mortality or a slight increase due to cardiovascular effects (and no suicide protection).
Limitations: Not controlled, so can’t rule out confounding by indication. In particular, lithium works better in classic bipolar (with few comorbidities and long periods of recovery), so that might skew the data.
Practice Implications
- Lithium carries health risks — renal, thyroid, parathyroid, toxicity — but the finding that it lowers overall mortality puts those risks in perspective.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
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