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 demonst
rated the efficacy of carbamazepine for the treatment of rapid cycling
bipolar disorder, the response to carbamazepine frequently deteriorat
es. Furthermore, its ability to auto-induce and hetero-induce drug met
abolism complicates its routine use. These findings suggest that subst
antial numbers of rapid cyclers do not respond to either carbamazepine
or lithium and that additional mood stabilizers are needed. Our recen
t findings on 101 rapid cycling bipolar patients continue to support t
he impression that valproate has marked antimanic efficacy and poor to
moderate antidepressant properties. Most patients with mixed states e
xhibited good antimixed state responses but then became depressed. Pre
dictors of a good antimanic response included decreasing or stable epi
sode frequencies and non psychotic mania. Predictors of a good antidep
ressant 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.