Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania.

Background: Few controlled studies examine the treatment of depressive features in mania.

Objective: To evaluate the efficacy of olanzapine, in combination with lithium or valproate, for treating depressive symptoms associated with mania.

Methods: Secondary analysis of a 6-week, double-blind, randomised study of olanzapine (5-20 mg/day) or placebo combined with ongoing valproate or lithium open treatment for 344 patients in mixed or manic episodes. This analysis focused on a dysphoric subgroup with baseline Hamilton Rating Scale for Depression (HRSD) total scores of 20 or over contrasted with non-dysphoric patients.

Results: In the dysphoric subgroup (n=85) mean HRSD total score improvement was significantly greater in olanzapine co-therapy patients than in those receiving placebo plus lithium or valproate (P<0.001). Substantial contributors to this superiority included the HRSD Maier sub-scale (P=0.013) and the suicide item (P=0.001). Total Young Mania Rating Scale improvement was also superior with olanzapine co-therapy.

Conclusions: In patients with acute dysphoric mania, addition of olanzapine to ongoing lithium or valproate monotherapy significantly improved depressive symptom, mania and suicidality ratings.