Lithium Treatment and Risk of Suicidal Behavior in Bipolar Disorder Patients

Background: Lithium may exert an antisuicidal effect in bipolar disorderpatients, but this hypothesis requires further testing by direct comparison of patientswith and without lithium treatment.

Method: Risk of life-threatening suicidal acts over time and associatedfactors were analyzed in 310 patients with DSM-IV bipolar I (N=186) or II (N=124) disorderevaluated for a mean of 8.3 years before, and prospectively during, a mean of 6.4 years oflithium maintenance in a mood disorder clinic; 185 were also followed for a mean of 3.7years after clinically discontinuing lithium.

Results: In 5233 patient-years of observation, 58 patients made 90suicide attempts (8 were fatal). Survival analyses with Weibull modeling with adjustmentsfor covariates indicated a highly significant 6.4-fold adjusted hazard ratio during versusbefore and 7.5-fold ratio after versus during lithium maintenance. Suicidal acts were morecommon early in the course of illness before lithium and were associated with priorsuicide attempts, greater proportion of time depressed, and younger age. After thediscontinuation of lithium, suicidal acts were more frequent in the first year than atlater times or before start of lithium treatment. Fatalities were 9 times more frequentafter versus during treatment.

Conclusion: Lithium maintenance was associated with marked reduction oflife-threatening suicidal acts, the number of which sharply increased after discontinuinglithium. Suicidal behavior was strongly associated with prior suicide attempts, more timedepressed, and younger age or recent onset. Greater attention to suicidal risk in patientswith bipolar depression and assessment of all proposed mood-stabilizing agents forantisuicidal effects are strongly encouraged.