Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

355 Use of atypical antipsychotic agentsbut each appears to carry less overall risk of extrapyramidal side-effects thanbenchmark conventional antipsychotic agents such as haloperidol (Seeman andTrallerico, 1999; Glazer, 2000a, b, c; Stanniland and Taylor, 2000; Kapur andSeeman, 2001). Consequently, atypical antipsychotics may, as a group, offersome improvements over older agents for treating patients with bipolar disorder,just as they have for schizophrenia. The differences or similarities across theatypical agents remain unclear; certainly they are not homogeneous in severalneuropharmacological actions of potential relevance to mood, such as effects onreceptors or neurotransmitter release of catecholamines, acetylcholine, glutamate,or gamma-aminobutyric acid. Further, as discussed below, clinical evaluation forthe other agents is lagging behind olanzapine. Therefore, it is too soon to determinewhether the agents have similar efficacy to conventional neuroleptics and toeach other for acute mania. Even less is known about relative impacts for diagnosticsubgroups and whether, in addition to olanzapine, any will be useful acrossphases of bipolar disorder, or, like conventional neuroleptics, be relevant mostly toacute mania.Starting in the late 1990s, a flurry of clinical trials have tested atypical antipsychoticagents for bipolar disorder. The authors of this chapter have contributedto the large portfolio of studies of olanzapine in bipolar disorder, several of whichyield information on treatment response of rapid-cycling patients and those withpsychotic or dysphoric mania. At this writing, data comparable in breadth ordepth to those on olanzapine are not yet available for other atypical antipsychoticagents. However, research is ongoing and one or more controlled acute maniastudies have been encouraged for risperidone (Hirschfeld et al., 2004; Sachs et al.,2002a, 2002b; Vieta et al., 2002), ziprasidone (Keck et al., 2003a), quetiapine(Sachs et al., 2004), and aripiprazole (Keck et al., 2003b). Data are not availablefor other potentially useful atypical agents currently under development, such asiloperidone.MethodWe briefly review available data on antipsychotic agents for the treatment ofpatients with bipolar disorder. The review is limited to controlled, double-blindclinical trials; these were identified through Medline search (as of March 2003);cross–referencing bibliographies of identified manuscripts; olanzapine trials conductedby us; and preliminary reports obtained at public scientific meetingsthrough 2002. This fourth method offers up-to-date information in this fastdevelopingfield, but carries significant limitations, such as less detailed presentationof methods and/or findings than is typical in manuscripts; incomplete peerreview; and the likelihood that some relevant presentations or posters were notavailable to us.