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This chapter reviews controlled findings regarding the impact of variant bipolar presentations to predicting treatment response with atypical antipsychotic agents. In the case of atypical antipsychotic medications, some findings are available regarding their use in patients with rapid-cycling bipolar disorder, as well as mania complicated by depression or psychosis. Antipsychotic agents may have unidirectional antimanic properties, tending to accelerate switch to depression or to cause dysphoria even in those without a primary mood disorder. The chapter primarily focuses on the relative response within diagnostic subgroups, especially psychotic versus non-psychotic, mixed versus manic, and rapid versus non-rapid cycling. Clozapine was the first of the atypical antipsychotic agents, with clinical trials in schizophrenia starting over three decades ago. Cerain other antipsychotic agents include risperidone, olanzapine, and aripiprazole. A diverse array of atypical antipsychotic medications has evidence of usefulness in mania, including lithium, anticonvulsants, antipsychotics, atypical antipsychotics, benzodiazepines, and calcium channel blockers.
Few controlled studies examine the treatment of depressive features in mania.
To evaluate the efficacy of olanzapine, in combination with lithium or valproate, for treating depressive symptoms associated with mania.
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.
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.
In patients with acute dysphoric mania, addition of olanzapine to ongoing lithium or valproate monotherapy significantly improved depressive symptom, mania and suicidality ratings.
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