Retrospectively, effects of long-term therapy with clozapine were evaluated in 121 out-patients. They were treated for 32 +/- 43 months in a daily dosage of 131 +/- 99 mg. Sixty nine patients were schizophrenic and had previously received one or more neuroleptics but with insufficient response or severe side effects. Nine patients suffered from tardive dyskinesia (TD), 44 patients had other diagnoses. Twenty two per cent of the schizophrenic patients improved slightly, 65% markedly and in 13% the symptoms nearly totally disappeared. Fourty per cent of chronic schizophrenics showed improvement of anergia. Eleven per cent of the patients with TD did not improve, 22% showed slight and 67% marked improvement. Clinically relevant side-effects occurred in 64% of patients: Generally sedation/hypotension, EG and ECG alterations, changes of white blood cell count, increase of liver enzymes and weight gain. EEG alteration correlated significantly with dosage of clozapine (P less than 0.01). In 6% of patients, severe side-effects led to discontinuation of clozapine treatment. No case of agranulocytosis occurred. Most patients tolerated the drug well and were compliant. Under careful control of hematological and other variables, the benefit/risk ratio of clozapine long-term treatment appears to be high and acceptable.
