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

365 Use of atypical antipsychotic agentsAripiprazoleAripiprazole is the most recently introduced antipsychotic agent, and at least twocontrolled monotherapy trials have been conducted in acute mania. One of thesehad positive findings (Keck et al., 2003b). Among hospitalized patients with acutemania, mean YMRS improved from baseline to the 3-week endpoint significantlymore frequently among patients treated with aripiprazole (29% reduction,n ¼ 130, mean dose 27.9 mg/day) compared to placebo (11%, n ¼ 132).Depression ratings significantly improved in aripiprazole-treated patients versusdepression (clinical global Impression-Bipolar severity of Depression). Theauthors do not address any of the potentially important response by subgroupinteractions, that is, based on rapid cycling, psychosis, or mixed state status. Dropoutrates were high in this 3-week study (58% on aripiprazole and 79% onplacebo). Measurements of extrapyramidal symptoms (Simpson–Angus andBarnes Akathisia scales) worsened significantly on aripiprazole compared toplacebo. Extrapyramidal adverse events reported more commonly in the aripiprazolethan placebo groups included akathisia (11% versus 2%), tremor (6% versus3%), and increased salivation (6% versus 1%), but it is not reported whether any ofthese findings were statistically significant.Use of atypical antipsychotic medications in mania: psychotic andnon-psychotic patientsA diverse array of medications has evidence of usefulness in mania, includinglithium, anticonvulsants, antipsychotics, atypical antipsychotics, benzodiazepines,and calcium channel blockers. There is little information on the relative effects ofsuch treatments, including whether a specific medication differentially targets asubset of manic symptoms. Nevertheless, in the case of antipsychotic agents, clinicalguidelines, unsurprisingly, are particularly supportive of their use for patients withpsychotic mania (and in some cases for more agitated or severely ill patients) a (Sachset al., 2000, American Psychiatric Association, 2002; Baldessarini, 2002).A secondary analysis was performed for the double-blind studies of olanzapine inacute mania to evaluate effectiveness for psychotic and non-psychotic subgroups, asa There is some evidence that, at least in the case of olanzapine, usefulness extends beyond more severely illpatients. In a previously unpublished secondary analysis of a 3-week olanzapine–divalproex monotherapycomparison for acute mania (Tohen et al., 2002a), treatment groups were divided into more and lessseverely ill groups by a median split of baseline YMRS. Among olanzapine-treated patients, baseline toendpoint improvement was similar in more and less severely ill patients. As compared to those receivingdivalproex, improvement was similar in the more severely ill cohort, but superior on olanzapine amongless ill patients. In that all patients in this study were hospitalized and had bipolar I disorder, the lessseverely ill patients probably still had relatively severe symptoms. Nevertheless, these data suggest that theusefulness of olanzapine, at least, extends beyond the sickest patients.