Perspectives on lithium treatment of bipolar disorder: action, efficacy, effect on suicidal behavior

To review studies of (A) whether lithium has a prophylactic action in bipolar disorder, (B) the efficacy of prophylactic lithium treatment in comparison with the efficacy of treatment with anticonvulsant drugs, and (C) the effect of lithium treatment on suicidal behavior.

Analysis of all relevant publications.

(A) The claim that a prophylactic action of lithium has never been satisfactorily demonstrated is based on wrong assumptions, biased selection of references, and unjustified generalizations. (B) In typical bipolar disorder lithium is significantly more efficacious than carbamazepine; in atypical bipolar disorder there is a non-significant trend for carbamazepine to be better than lithium. Valproate has not been proven prophylactically efficacious in typical bipolar disorder; in atypical bipolar disorder it may have an effect, but it has not been compared with that of lithium. (C) A significant association has been found between prophylactic lithium treatment, on the one hand, and reduced mortality and suicidal behavior, on the other. No such association has been reported for prophylactic treatment with other mood stabilizers.

In bipolar disorder the choice of prophylactic drug must be based on a weighing of efficacy against tolerability, interactions, ease of management, use during pregnancy and lactation, and expense. Lithium should be the preferred prophylactic drug in patients with typical bipolar disorder and in patients who are at high risk of committing suicide, that is, patients with severe depressions or depressions combined with persistent suicidal ideas or with suicide attempts in the past.