Antipsychotic intervention in treatment-resistant schizophrenia

The studies described in part 1 of this thesis focus on the effect of reducing the dose or discontinuing antipsychotic medication in patients with chronic schizophrenia and on the effect and side effects of optimizing antipsychotic dosing or switching to ziprasidone, with a view to improving the antipsychotic treatment of long-stay patients currently on high doses of antipsychotics. From meta-analyses we concluded that the risk of relapse was highest for doses lower than 3-5 mg haloperidol-equivalents per day, and that rather slow reduction was protective. In a RCT we found very limited advantage of the atypical antipsychotic ziprasidone over dose reduction of conventional antipsychotics. Ziprasidone was slightly better for extrapyramidal side effects and for cognitive function.
The studies reported in part 2 focused on optimizing the next step in the pharmacological treatment protocol, clozapine, to improve outcomes. Some patients responded to clozapine when blood levels were higher than the so called therapeutic threshold, indicating that some patients need higher levels, although this generally does not apply to older patients. In a trial of blood sampling methods patients strongly preferred capillary testing, what might boost clozapine prescribing rates. The performance of the point-of-care sampling method proved to be comparable to venous sampling for leukocytes and granulocytes. We further describe case studies of add-on filgrastim in the case of clozapine-induced agranulocytosis, and of the influence of oral contraceptives, which raise clozapine levels. Lastly, in a review practical advises have been formulated regarding COVID-19 infections in clozapine users.