Dose reduction or switch to ziprasidone followed by clozapine therapy: what works better in a long stay schizophrenia group?

Patients treated with ziprasidone reveal fewer negative symptoms on the PANSS negative symptoms sub-scale and/or better scores on the CGI therapeutic effects sub-scale (CGI-TE) than patients treated with low-dose conventional antipsychotics (5 mg/day haloperidol or equivalent doses).
For patients not effectively treated in this regimen clozapine will be superior.

Baseline measurements (Phase A): weeks 0, 6 and 12.
Dose adjustment and switch phase (Phase B): variable, between 0 and 24 weeks following baseline time points.
One-year treatment and observation phase (Phase C): weeks 4, 16, 34 and 52, following dose adjustment and switch phase.

Afterwards patients are treated with clozapine and followed for another year, with evaluations 12 weeks after an adequate plasma level and at the end of the study.



Measurements: symptoms of psychosis (PANSS), clinical impression of symptoms (CGI), depression (MADRS), neurocognitive symptoms (NPO), general functioning (REHAB), social function and aggression (SDAS), extrapyramidal and general side effects (AIMS, Fahn-Marsden, UPDRS, BARS and UKU), subjective well being (SWN), quality of life (MANSA), addiction severity (ASI), weight, length and laboratory measurements.

The study consists of three consecutive phases:
12-week pre-switch observation phase (Phase A): during 12 weeks repeated baseline ratings will be done under fixed medication schedules without change of previously used medication (stable baseline measurements).

Dose adjustment and switch phase (Phase B): At random one group of patients (group 1) continues to use conventional antipsychotics. The other group (group 2) is switched to ziprasidone. In group 1 doses of >5mg/day haloperidol equivalents will be reduced to 5 mg/day. Reduction will take a maximum of 24 weeks. Type of antipsychotic and route of administration will not be changed. In group 2, the equivalent of 5 mg/day of haloperidol of the conventional antipsychotic will be replaced by ziprasidone in the first 6 weeks of the double blind treatment phase. The remaining dose of the conventional antipsychotic is reduced similar to group 1.
One-year treatment and observation phase (Phase C): after the dose adjustment and switch phase patients are treated and observed for 52 weeks.

Afterwards patients are treated with clozapine and followed for another year, with evaluations 12 weeks after an adequate plasma level and at the end of the study.