Clinical correlates of therapeutic response in bipolar disorder

Interest in the factors associated with responsiveness to therapy in bipolar disorder has increased with evidence that lithium has differential rather than uniform effectiveness in bipolar disorder, and also with the broadening of therapeutic options, illustrated especially by the use of divalproex sodium (valproate). Lithium is effective acutely in patients with pure or elated mania, and in its prophylaxis, but may worsen depressive symptoms in such patients when used for long-term maintenance therapy. The nature of previous responses to lithium treatment predicts the type of response that can be expected during a further episode of the disorder. Mixed mania, secondary mania, and mania associated with substance abuse--as well as rapid cycling --generally respond poorly to lithium therapy. Divalproex sodium has a broader spectrum of efficacy and fewer factors that determine differential responsiveness. Data related to treatment with carbamazepine are sparse, but patients with rapid cycling may respond less well to this agent; on the other hand, limited data support the utility of carbamazepine in bipolar patients with extreme psychosis, including those with mood-incongruent features. Both classical and atypical neuroleptics (e.g. olanzapine) could profitably be used in acute mania and mixed states. Lamotrigine has recently been shown effective in bipolar depression and rapid cycling. Patients unresponsive to a single agent may show improvement with combined regimens, though this impression is based more on clinical experience than controlled randomized assignment.