Young RC, et al. - This randomized double-blind controlled trial was performed to investigate the efficacy and tolerability of lithium and divalproex in the treatment of mania in older patients with bipolar disorder. The authors found both lithium and divalproex to be adequately tolerated and efficacious. Over 9 weeks, lithium was correlated with a greater reduction in mania scores.

• The tolerability and efficacy of lithium carbonate and divalproex were compared in 224 inpatients and outpatients age 60 or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode.
• The authors randomly assigned participants, under double-blind conditions, to treatment with lithium (target serum concentration, 0.80-0.99 mEq/L) or divalproex (target serum valproate concentration, 80-99 μg/mL) for 9 weeks.
• For this study, participants with an inadequate response after 3 weeks received open adjunctive risperidone.
• They hypothesized that divalproex would be better tolerated and more efficacious compared to lithium.
• They evaluated tolerability based on a measure of sedation and on the proportions of participants achieving target concentrations.
• They assessed efficacy with the Young Mania Rating Scale (YMRS).

• For lithium and divalproex, attrition rates were similar (14% and 18% at week 3 and 51% and 44% at week 9, respectively).
• In terms of sedation, the groups did not differ significantly.
• In the lithium group, participants tended to experience more tremor.
• In the lithium and divalproex groups, similar proportions of participants achieved target concentrations (57% and 56%, respectively).
• In this study, a longitudinal mixed model of improvement (change from baseline in YMRS score) favored lithium (change in score, 3.90; 97.5% CI=1.71, 6.09).
• Between the lithium and divalproex groups, 9-week response rates did not differ significantly (79% and 73%, respectively).
• Between groups, the need for adjunctive risperidone was low and similar (17% and 14%, respectively).