Tolerability and Therapeutic Effect of Clozapine. A Retrospective Investigation of 216 Patients Treated with Clozapine for Up to 12 Years

Two hundred and sixteen psychiatric patients (183 men and 33 women) hospitalized in Sct. Hans Hospital were treated with clozapine between 1971-1983. All had been treated previously with one or more neuroleptic(s) and had either failed to respond adequately, or their response was limited by side effects. Eighty-five patients were treated exclusively with clozapine, while the remaining 131 received additional medication, mainly other neuroleptic drugs. The mean clozapine dosage was 317 mg/day (range 50-1200), and the mean duration of treatment was 23/4 years (range 1/12-12). The tolerability to clozapine was determined by an evaluation of haematological changes, pronounced side effects and mortality. One patient treated with clozapine (8 months) and nitrofurantoin (8 days) developed a reversible granulocytopenia. One patient (treated with a combination of drugs) had clinically insignificant depression of the leucocytes and three of segmented granulocytes. Seven had a reduction in thrombocytes. Two patients developed cardiac insufficiency, and four epileptic seizures. None of the patients treated exclusively with clozapine developed neurological side effects. A global estimation of therapeutic effect revealed that clozapine alone or in combination with other neuroleptic drugs was significantly better than previous antipsychotic therapy, although 47-63% of the patients showed no change. It is concluded that clozapine is a potent antipsychotic drug offering particular advantages in the treatment of schizophrenic patients with a pronounced symptomatology and tendency towards developing extrapyramidal side effects. Caution is advised in patients with cardiac insufficiency and epilepsy. There appears to be a slight risk of granulocytopenia, and therefore the present monitoring of WBC should continue in order to prevent this reaction and to obtain more complete information regarding risk of granulocytopenia.