Article

Long-Term Efficacy and Tolerability of Clozapine Combined with Ziprasidone or Risperidone

Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, University of Heidelberg, Mannheim, Germany.
Pharmacopsychiatry (Impact Factor: 2.17). 08/2010; 43(6):216-20. DOI: 10.1055/s-0030-1254089
Source: PubMed

ABSTRACT Treatment resistance in schizophrenia often leads to add-on of atypical antipsychotics to clozapine.
In a randomized trial, we recently obtained evidence for comparable efficacy and differential side effects of clozapine in combination with ziprasidone (CZ, N=12) versus risperidone (CR, N=12). Here, we present the open-label, long-term evaluations of these patients after 26 and 52 weeks.
Sustained improvements of psychopathology as assessed by PANSS (positive and negative syndrome scale), SANS (scale for the assessment of negative symptoms), and HAMD (Hamilton depression scale) were documented in both subsamples being treated according to protocol, while dropouts reduced the study sample after 26 (CZ: reduced by -4; CR: -2) and 52 weeks (CZ: -0; CR: -5). We observed a slight increase of akathisia in the CZ group whereas general clozapine-associated side effects improved.
The combinations of clozapine with ziprasidone or risperidone exhibit long-term efficacy, but the level of evidence is limited. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.

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    • "Also ziprasidone has been successfully added to clozapine in numerous case reports and open trials. A head-to-head comparison of ziprasidone or risperidone combined with clozapine revealed similar immediate and long-term efficacy on treatment-resistant schizophrenic symptoms at a diverging range of side effects regarding serum prolactin, extrapyramidal symptoms, and QTc-prolongation (Kuwilsky et al., 2010[16]; Zink et al., 2009[35]). "
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    • "Some studies demonstrate the efficacy of ziprasidone in treatment-resistant or treatment-intolerant patients with schizophrenia. Recently, one head-to-head trial comparing the combination of clozapine with risperidone (CR) versus clozapine with ziprasidone (CZ), differed with a marked prolactin increase in the CR group and a statistically significant QTc elongation in the CZ group46,47 Many other studies and anecdotal reports also report coadministration of ziprasidone with clozapine. In some cases, ziprasidone has been added to clozapine in attempts to reduce metabolic side effects as well as to optimize antipsychotic efficacy. "
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