Background: This pilot study compared the efficacy of lithium plus divalproex sodium with the efficacy of lithium alone for the continuation and maintenance treatment of patients with bipolar I disorder.
Method: Twelve patients with bipolar I disorder as defined by the DSM-III-R were recruited and followed prospectively for up to 1 year. Each subject received lithium at serum levels of 0.8 to 1.0 mmol/L and a management/education session weekly or every 2 weeks. By random assignment, subjects received either divalproex sodium or placebo in conjunction with lithium. Divalproex sodium was adjusted to achieve a serum concentration of 50 to 125 micrograms/mL. Adjunctive medications were used on an as needed basis to treat psychosis, depression, and anxiety. The course of illness was monitored through use of the Longitudinal Interval Follow-up Examination.
Results: Subjects treated with the combination of lithium and divalproex were significantly less likely to suffer a relapse or recurrence (p = .014), but were significantly more likely to suffer at least one moderate or severe adverse side effect (p = .041). There was no significant difference between groups in the use of adjunctive medication.
Conclusion: These results provide preliminary evidence of the risks and benefits of combining lithium with divalproex sodium for the continuation and maintenance treatment of bipolar I disorder.