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 lithium, divalproex or placebo for manic episodes had comprehensive evaluations of illness history. We used non-linear curve fitting of change in Manic Syndrome Score (MSS) of the Schedule for Affective Disorders and Schizophrenia (SADS) versus previous depressive or manic episodes to investigate their relationships to MSS improvement. Results: Response to lithium, but not to divalproex or placebo, worsened with increased depressive or manic episodes. More than 11 manic, or four depressive, episodes was associated with response to lithium that did not differ from placebo. Effects of previous depressive and manic episodes appeared independent, and could not be accounted for by increased rapid cycling or mixed states. Conclusion: At least four previous depressive or 12 previous manic episodes are associated with reduced antimanic response to lithium.