• bipolar disorder;
  • depression;
  • lithium;
  • mania;
  • meta-analysis;
  • suicide;
  • treatment

Objective: To compare suicide rates with vs. without long-term lithium treatment in major affective disorders.

Method: Broad searching yielded 22 studies providing suicide rates during lithium maintenance; 13 also provide rates without such treatment. Study quality was scored, between-study variance tested, and suicide rates on vs. off lithium examined by meta-analyses using random-effects regression methods to model risk ratios.

Results: Among 5647 patients (33 473 patient-years of risk) in 22 studies, suicide was 82% less frequent during lithium-treatment (0.159 vs. 0.875 deaths/100 patient-years). The computed risk-ratio in studies with rates on/off lithium was 8.85 (95% CI, 4.12–19.1; P<0.0001). Higher rates off-lithium were not accounted for by treatment-discontinuation.

Conclusion: Suicide risk was consistently lower during long-term treatment of major affective illnesses with lithium in all studies in the meta-analysis, including the few involving treatment-randomization.