A large subgroup of
lithium-resistant manic patients are rapid cyclers and as many as 82% of them exhibit poor responses to
lithium. Thus, a substantial percentage of poor responses to
lithium is accounted for on the basis of rapid cycling. Although controlled trials have demonstrated the efficacy of
carbamazepine for the treatment of rapid cycling
bipolar disorder, the response to
carbamazepine frequently deteriorates. Furthermore, its ability to auto-induce and hetero-induce
drug metabolism complicates its routine use. These findings suggest that substantial numbers of rapid cyclers do not respond to either
carbamazepine or
lithium and that additional mood stabilizers are needed. Our recent findings on 101 rapid cycling bipolar patients continue to support the impression that
valproate has marked antimanic efficacy and poor to moderate
antidepressant properties. Most patients with mixed states exhibited good antimixed state responses but then became depressed. Predictors of a good antimanic response included decreasing or stable episode frequencies and non psychotic
mania. Predictors of a good
antidepressant response were non psychotic
mania worsening over the years of the illness and absence of
borderline personality disorder comorbidity. These open prospective trials, as well as other positive reports of
valproate's efficacy in bipolar rapid cycling, await replication with ongoing, controlled maintenance trials.