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Published online by Cambridge University Press: 13 June 2014
Objectives: To examine the reasons why manic-depressive patients often fail to respond to lithium and, the chief purpose of this paper, to review the present state of knowledge concerning alternative pharmacotherapies to lithium in this disorder. Method: Literature review. Findings: Lithium produces a clinically useful effect in 70-80% of cases. Factors such as non-compliance, side-effects, serum levels, and enduring psychosocial influences on the patient must be considered before treatment failure is diagnosed. Carbamazepine is the most studied alternative drug to date, and the most likely predictors of response to this agent are rapid-cycling, absence of a family history of affective disorder, mania, severe illness, and non-response to lithium. Conclusions: In view of the 20-25% of patients who do not respond to lithium, and the increased likelihood that lithium-responders may fail to respond again once the drug has been stopped for a period, further research is needed to find better and safer prophylactics against depression in bipolar disorders and to refine our knowledge of the indications for use of those already available.