Summary

This meta-analysis of 48 randomized controlled trials found that lithium significantly reduced the risk of suicide and death from any cause, when compared with placebo.

Design

• Meta-analysis of 48 randomized controlled trials (n=6,674 patients) comparing lithium with placebo or alternative drug for long term treatment of mood disorders.
  • 12 trials: unipolar depression
  • 19 trials: bipolar disorder
  • 17 trials: mix of unipolar, bipolar and schizoaffective disorders.
• Included trials were published between 1968-2013.
• Long term treatment was defined as treatment with a minimum duration of three months.
• Comparator treatments (aside from placebo) included amitriptyline, carbamazepine, valproate, fluoxetine, fluvoxamine, imipramine, lamotrigine, mianserin, maprotiline, nortriptyline, olanzapine, phenelzine, quetiapine, and thyroid hormone.
• Primary outcomes: suicide, deliberate self harm, and all-cause mortality.

Results

• Bipolar disorder:
  • Lithium was associated with lower risk of suicide (OR 0.13, 95% CI 0.03-0.66) when compared with placebo. Data from four studies, with a total of 0 suicides in 244 patients taking lithium, compared with 6 suicides in 241 patients taking placebo.
  • Lithium was associated with lower risk of death from any cause (0.38, 0.15-0.95) when compared with placebo. Data from eight studies, with a total of 5 deaths in 392 patients taking lithium, compared with 14 deaths in 390 patients taking placebo.
• Unipolar depression:
  • Lithium was associated with lower risk of suicide (0.36, 0.13-0.98) when compared with placebo. Data from three studies, with a total of 0 suicides in 143 patients taking lithium, compared with 5 suicides in 137 patients taking placebo.
  • Lithium was associated with lower risk of death from any cause (0.13, 0.02-0.76) when compared with placebo. Data from seven studies, with a total of 4 deaths in 291 patients taking lithium, compared with 12 deaths in 286 patients taking placebo.
• Risk of suicide or death from any cause did not differ significantly between lithium and any other active treatment.

Reference

Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013;346:f3646. doi:10.1136/bmj.f3646.