Introduction
While diagnostic criteria for mixed states continue to be developed, treatment outcome of mixed vs. non-mixed populations may provide indirect evidence of course of illness and severity which could validate changes in our current definition of “mixed” states.
Methods
Clinical trial data for both mania and depression were reviewed for secondary outcome assessment of mixed vs. non-mixed treatment response.
Results
In all analyzed studies, mixed manic groups had response rates similar to non-mixed manic groups. The only dysphoric manic vs. non-dysphoric manic analysis was a secondary analysis of a comparison study of lithium vs. divalproex vs. placebo. The presence of dysphoric mania was predictive of non-response to lithium while an irritable-dysphoric subtype was predictive of response to divalproex. Mixed depression and acute treatment response was not standardized amongst studies. In one study of OFC vs. olanzapine vs. placebo, the mixed depressive group had a response rates similar to the non-mixed depressive group for OFC, but not olanzapine. Bipolar Collaborative Network clinical trials reported that mixed depression at baseline was significantly less likely to achieve remission by study endpoint vs. non mixed depression.
Discussion:
Recognized by current DSM, mixed mania is well defined and as a whole, responded equally well to most antimanic agents. Less well defined and studied, dysphoric mania appears to preferentially respond to divalproex. There are no operationalized criteria for mixed depression, but non-standardized treatment outcome would suggest lower treatment response rates than non-mixed depression with the exception of OFC.