Many studies have shown that treatment resistance is a substantial problem in schizophrenic patients, with 20-30% of patients responding only partially and about 7% showing no response to antipsychotic treatment. Clozapine has been consistently shown to be effective in this subgroup of schizophrenic patients. It is still the drug of choice, despite the restricted indication and the need for a careful evaluation of side effects. Recently, several double-blind studies of newer atypical antipsychotics have been conducted in therapy-resistant patients. Three studies compared risperidone with clozapine, one study zotepine with clozapine and two others olanzapine with dozapine. One study compared the efficacy of clozapine, olanzapine, risperidone with one another and with haloperidol. In these studies, dozapine showed increasing superiority the more restrictive the criteria for therapy-resistance chosen. Olanzapine was found to be as effective as clozapine and was better tolerated. However, the results of studies comparing different atypical anti-psychotics have to be interpreted carefully because of their limited number as well as methodological problems. Case studies also indicate the efficacy of combining different atypical antipsychotics, but no systematic research on this issue has been done so far.
