Two or more combined drugs may be needed to treat rapid-cycling bipolar disorder.(Bipolar Disorder)

Divalproex may not be any more effective than lithium in treating patients with rapid-cycling bipolar disorder. This is one of the conclusions drawn from a 20-month, double-blind maintenance trial which hypothesized that divalproex would be significantly better than lithium in managing rapid cycling on a long-term basis. The results are surprising in view of earlier studies that showed a poor response to lithium in 72%-82% of patients with rapid-cycling bipolar disorder (1-2) and efficacy of divalproex in reducing manic and depressive symptoms in this subgroup of patients who had not responded well to lithium. (3)

According to lead investigator Joseph R. Calabrese, M.D. and colleagues, "The results from this trial are consistent with rapid cycling being a nonspecific predictor of poor outcome to treatment." The new findings highlight the need for future maintenance studies that combine mood stabilizers "possessing a complementary spectrum of activity, including at least one agent that stabilizes mood from below baseline." Calabrese is Director of the National Institute of Mental Health (NIMH) Bipolar Research Center at University Hospitals of Cleveland and Professor of Psychiatry at Case Western Reserve University School of Medicine.

The study is unique in terms of its duration. It is the longest recently conducted maintenance study in bipolar disorder, having a 6-month open-label acute stabilization phase, followed by a 20-month maintenance phase, allowing an assessment of relapse rates over a clinically significant period of time, write Calabrese and colleagues.

Open-label phase

During the open-label phase, only 24% of the intent-to-treat sample responded to combination therapy with lithium and divalproex. [See box for study details].

Among the 65 patients not responding to treatment during the open-label phase, 74% experienced …