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

INTERVENTION: 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. CONDITION: Schizoaffective disorder, Schizophrenia, Therapy resistent ; ; PRIMARY OUTCOME: • PANSS negative symptoms scale ; ; • CGI therapeutic effect scale; SECONDARY OUTCOME: • Number of responders ; ; • NPO (neurocognitive functioning) : see addendum to the protocol ; ; • EPS (side effects: extra pyramidal): see addendum to the protocol ; ; • PANSS positive symptoms scale, general psychopathology scale and total scale ; ; • CGI severity of illness scale, global improvement scale ; ; • MADRS (symptoms of depression) ; ; • REHAB (general functioning) ; ; • SDAS (social dysfunction and aggression) ; ; • UKU (side effects) ; ; • SWN (subjective well‐being) ; ; • Lancashire (quality of life) ; ; • Anticholinergic medication ; ; • Escape‐ and prn.‐ medication ; INCLUSION CRITERIA: ‐DSM‐IV diagnosis of schizophrenia or schizoaffective disorder, based on a SCID interview. ‐Use of conventional antipsychotics, p.o. or i.m. (depot‐preparations), and the patient consenting to use oral medication. ‐Psychotic symptoms having been present during at least the past 2 years, more or less continuously, confirmed by information from the clinical file and the SCID interview. ‐Stable symptomatology and no changes in medication during the last 3 months before inclusion. ‐Able to comply with the study design. ‐Both sexes. ‐Age „d18 years. ‐In‐patients. ‐Judicially (R.M. = forced hospitalization) or voluntarily staying in the hospital (I.B.S. excluded). ‐Written informed consent from patient and/or representative.