Bipolar Disorder: Increasing the Effectiveness and Decreasing the Side Effects of Treatment

Placebo-controlled trials of SGAs showed similar changes in YMRS scores and response rates, but the best way to establish relative efficacy is to conduct a head-to-head comparator trial. To date, only one study compared olanzapine(Drug information on olanzapine) with risperidone(Drug information on risperidone) in the treatment of acute mania.³⁸ The 3-week trial involved 329 patients with nonpsychotic acute mania and showed no differences in YMRS scores or response rates between the 2 groups. However, the mean improvement in MADRS scores was statistically greater with olanzapine than with risperidone.

Polytherapy

Polytherapy is commonly used in the treatment of initial and refractory episodes of mania. This generally involves the combination of a mood stabilizer with an SGA. Such combinations are associated with a 20% higher response rate than individual mood stabilizers.¹¹ However, polytherapy is also associated with significantly higher rates of adverse effects.³⁹

Four studies analyzing combination therapy for the treatment of mania in adults have been published.^39-42 In addition, one combined analysis included the published quetiapine(Drug information on quetiapine) study and an unsuccessful quetiapine study that has not been published.⁴³ All studies were double-blind, randomized, and placebo-controlled. Study duration was typically 3 weeks, although the olanzapine trial lasted 6 weeks.

FIGURE

YMRS score reduction with combination therapy

YMRS reduction and clinical response. Olanzapine, risperidone, and quetiapine, in combination with valproate(Drug information on valproate)/divalproex or lithium(Drug information on lithium), resulted in statistically significant reductions in YMRS scores and response rates compared with valproate/divalproex or lithium plus a placebo. In the olanzapine polytherapy group, YMRS scores decreased by 13.1, with a response rate of 68%.³⁹ Risperidone combination therapy resulted in a YMRS score reduction of 14.3 and a response rate of 53%.⁴⁰ Quetiapine, in the combined analysis of 2 polytherapy trials, was found to reduce YMRS scores by 15.3 and produce a 56% response rate.⁴³Overall, polytherapy was associated with a mean reduction in YMRS scores of 14.2 and a response rate of 59%. In comparison, monotherapy was associated with an average YMRS score reduction of 9.8 and a clinical response of 39% (Figure).