PART C:
Future Research Needs

While a number of large, double-blind, controlled trials in bipolar disorder have been conducted since the publication of the first guideline on the treatment of bipolar disorder in 1994 (5), many significant questions remain regarding optimal use of the available treatments. The introduction of new pharmacotherapies, including newer anticonvulsants and atypical antipsychotics, has also led to a need to directly compare traditional and newer interventions. Moreover, fundamental questions remain to be addressed about the nature of bipolar disorder itself.

VI. GENERAL PRINCIPLES

1. Is there a more clinically and scientifically useful definition of a "mood stabilizer"? Do newer agents (e.g., atypical antipsychotics and anticonvulsants) have true "mood-stabilizing" properties?
2. What is the relationship of bipolar I disorder, bipolar II disorder, and possible "bipolar spectrum" illnesses?
3. To what extent do patients with bipolar I and bipolar II disorder respond differentially to treatment?

VII. ACUTE TREATMENT

A. Manic and Mixed Episodes

1. What medication dosage and treatment duration can be considered an adequate trial?
2. In what circumstances is combination therapy favored over monotherapy?
3. Do different atypical antipsychotics exert different antimanic effects? Which combinations are most efficacious?
4. Can true antimanic properties of medications be distinguished from sedative properties of medications?

B. Depressive Episodes

1. How effective are newer antidepressants, such as SSRIs, in treating bipolar depression? How and when can they best be combined with other pharmacotherapies, such as lithium and valproate?
2. Do the different antidepressants have different relative efficacies?
   What medication dosage and treatment duration can be considered an adequate trial?
3. In treating an episode of bipolar depression, at what point in time is the addition of an antidepressant appropriate?

C. Rapid Cycling

1. Which pharmacotherapy regimens are most effective in the treatment of rapid cycling?
2. Do newer antidepressants or other medications truly differ in their propensity to induce rapid cycling or switches into hypomanic episodes?

VIII. MAINTENANCE TREATMENT

1. What is the efficacy of newer agents in maintenance pharmacotherapy?
2. What are the predictors of response or nonresponse to maintenance pharmacotherapy?
3. What is the optimum treatment of residual or sub-threshold symptoms?
4. How can the side effects seen with all maintenance pharmacotherapies be minimized?
5. To what extent do interventions in bipolar disorder improve functional status rather than symptoms?

IX. PSYCHOSOCIAL INTERVENTIONS

1. What are the relative efficacies of (and indications for) different psychotherapeutic approaches in the acute and maintenance phases of treatment?
2. What are the elements of psychotherapy that are critical to its efficacy?