Abstract
Introduction Suicidal behavior is strongly associated with depression in major depressive (MDD)
and bipolar (BD) disorders, especially with associated behavioral activation, dysphoria,
or agitation. A rare intervention with evidence of suicide risk-reducing as well as
mood-stabilizing effects in mood disorder patients is lithium.
Methods We reviewed available research evidence on associations of long-term treatment with
lithium with risk of suicidal behavior. We meta-analyzed 12 randomized trials in 10
reports (with at least 1 suicide in either treatment arm) including both BD and MDD
subjects, with particular attention to comparisons of lithium with placebo or other
pharmacological treatments. We also summarized ecological studies on lithium concentration
in local drinking water and reported suicide rates.
Results We found substantial reduction of risks of suicide and attempts with long-term lithium
treatment, particularly in depressive phases of BD and in MDD. Risk of suicidal behavior
was higher in mixed (agitated-dysphoric) states than in manic or hypomanic periods.
Risk of suicide fatality, specifically, was lower with lithium than with placebo and
probably with mood-altering anticonvulsants or antidepressants.
Discussion Long-term treatment with lithium has growing evidence of suicide- and attempt-sparing
effects, probably greater than with anticonvulsants or antidepressants; antipsychotics
remain to be tested adequately. However, the ethical and scientifically adequate design
and conduct of trials of treatments aimed at suicide prevention remain challenging
and underdeveloped.
Key words
anticonvulsants - antidepressants - antipsychotics - bipolar I and II disorders -
lithium - major depressive disorder - suicide
