Treatment refractory
mania is a common clinical problem. Unfortunately, the treatment of acute
mania refractory to standard antimanic and mood-stabilizing medications has not been well studied. This review will discuss the definition, evaluation, and differential diagnosis of treatment refractory
mania; the definition of an adequate treatment trial for acute
mania; the identification of predictors of treatment response; and clinical trials in treatment refractory
mania. Computerized searches of the medical literature regarding treatment refractory
mania were undertaken using Paperchase (1966-2001), and bibliographies of all articles identified were reviewed to identify all relevant case reports, case series, clinical trials, and methodologic and phenomenologic reports. Operational definitions of treatment refractory
mania were proposed based on sequential nonresponse to adequate trials of
antimanic agents. The average time of onset of
antimanic agents studied in randomized trials was 1 to 2 weeks. Clinical tools for assessing treatment response retrospectively and prospectively appear to have an important role in managing medication treatment in patients with
bipolar disorder. Relatively few reliable predictors of treatment response to established
antimanic agents have been identified. However, these predictors represent important factors in treatment selection to minimize the probability of nonresponse. Very few randomized, controlled trials of
antimanic agents have been conducted in patients with treatment refractory
mania. Field testing of treatment algorithms and systematic collection of data from naturalistic treatment studies should provide much-needed data regarding the efficacy of
antimanic agents in treatment refractory
mania.