Mania: differential effects of previous depressive and manic episodes on response to treatment

Objective: We compared effects of previous depressive or manic episodes on antimanic response. Method: in-patients in a parallel-groups, double-blind comparison of lithiu m, divalproex or placebo for manic episodes had comprehensive evaluations o f illness history. We used non-linear curve fitting of change in Manic Synd rome Score (MSS) of the Schedule for Affective Disorders and Schizophrenia (SADS) versus previous depressive or manic episodes to investigate their re lationships to MSS improvement. Results: Response to lithium, but not to divalproex or placebo, worsened wi th increased depressive or manic episodes. More than 11 manic, or four depr essive, episodes was associated with response to lithium that did not diffe r from placebo. Effects of previous depressive and manic episodes appeared independent, and could not be accounted for by increased rapid cycling or m ixed states. Conclusion: At least four previous depressive or 12 previous manic episodes are associated with reduced antimanic response to lithium.