CLINICAL STATES AND COURSE SPECIFIERS:
IMPLICATIONS FOR TREATMENT

There is growing evidence that the course or symptoms of bipolar disorder, particularly the presence of rapid cycling or mixed states, may have major clinical significance. Bipolar disorder can manifest with a variety of clinical presentations along the course of a lifetime. Mixed states, rapid cycling and psychosis may occur as phases of the disorder. Rapid cycling and mixed states are associated with an increased risk of suicide and substance use. Rapid cycling and psychotic features may also be more consistently present and be part of a "sub-type" of the disorder. These factors may influence the use of different medications and combinations of medications at different periods during the treatment of bipolar disorder. There is significant evidence that monotherapy with a mood stabilizer over a lifetime benefits only a minority of patients. Hence, classifying the bipolar disorder into specific "sub-types", like mixed states, rapid cycling and or psychosis, at different points in the course of the illness may allow more specific choice of biological treatment.

Classical Bipolar I with three or fewer cycles per year runs a less turbulent course than bipolar disorder with rapid cycling, and responds very well to Lithium, although it also responds to Divalproex Sodium (DVPX) and Carbamazepine (CBZ). Bipolar II Disorder has not been studied as carefully as Bipolar I Disorder, but there is no evidence to suggest that one mood stabilizer is more efficacious than another in this condition. However, future work may show that certain compounds may have both mood stabilizing and superior antidepressant properties, hence making them more suitable for use in Bipolar II Disorder. Rapid Cycling is associated with relatively better response to Divalproex and failure to respond to Lithium and, possibly, Carbamazepine. Rapid Cycling may be a phase in the course of a bipolar disorder, whereas in some subjects it may also be a type of disorder. It can be induced by antidepressant treatment, particularly tricyclic antidepressants (TCAs), and can sometimes be precipitated by abrupt discontinuation of any psychotropic medication in bipolar disorder. Mixed State needs to be screened for in every mania and depression as it is more common than previously thought. It responds to DVPX or CBZ, and has a relatively poorer response to Lithium. The newer anticonvulsants, like Lamotrigine and Gabapentin, hold promise, particularly in bipolar depression, but data from double blind controlled trials should be studied before recommendations about these compounds can be made.