Aim. To confirm the efficacy and tolerability of ziprasidone as adjunctive therapy in bipolar patients partially responding to clozapine or with persisting negative symptoms, overweight, or with metabolic syndrome. Methods. Eight patients with psychotic bipolar disorder were tested with the BPRS, the HAM-D, and the CGI at T0 and retested after 2 weeks (T1). Plasma clozapine and norclozapine levels and BMI were tested at T0 and T1. Results. Ziprasidone was well tolerated by all the patients. BPRS and HAM-D scores were reduced in all patients. BMI was reduced in patients with a BMI at T0 higher than 25. Plasma levels of clozapine and norclozapine showed an irregular course. 1. Introduction Atypical antipsychotics (also known as second generation antipsychotics, SGAs) have proven effective in the treatment of schizophrenia and schizoaffective disorder yielding improvements in both positive and negative symptoms [1–11]. Many SGAs are also indicated for the treatment of the different phases of bipolar disorder (BD) (i.e. acute mania and depression and maintenance) in monotherapy and in association with mood stabilizers. The SGAs vary widely in their efficacy/tolerability profiles allowing a better personalization of pharmacotherapy [9, 12–15]. SGAs have represented a meaningful improvement in clinical management of BD but a substantial percentage of patients keep on experiencing relapses, continuous cycling, persistent affective and psychotic symptoms, and functional deterioration [14, 16, 17]. Clozapine, the “gold standard” of SGAs, has never been approved for the treatment of bipolar disorder, though it has showed efficacy in acute mania [18–22] and in the treatment of severe psychotic bipolar disorder. This latter has been suggested to represent a possible intermediate clinical phenotype placed in the continuum of major psychoses bridging typical bipolar disorder to schizophrenia through schizoaffective disorder [9, 20, 21, 23–28]. A significant percentage of patients with severe psychotic bipolar disorder exhibit poor or incomplete response to usual monotherapy and combination treatments of adequate dosages and duration. Clozapine has been proposed as a suitable rescue choice to manage such complex conditions including uncontrollable mood instability, agitation, insomnia, psychosis, and aggressiveness. Unfortunately, even the addition of clozapine to the therapeutic strategy often leads only to a partial response [29, 30]. Moreover, clozapine treatment is burdened with several short- and longer-term side effects such as sialorrhoea, oversedation,
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