Dose-related effects of clozapine on tardive dyskinesia among “treatment-refractory” patients with schizophrenia

Clozapine has been reported to improve tardive dyskinesia (Simpson 1978). 23 DSM-IIIR “treatment-refractory” schizophrenics (mean age 46±8.5 years) received 100, 300, and 600 mgs of clozapine (CLZ) for 16 weeks each in a double-blind randomized cross-over design. Patients were evaluated on a weekly basis across a naturalistic baseline (BL) of 4 weeks; haloperidol (HLP) 10mg for 4 weeks and 3 CLZ phases. After 16 weeks on the initial CLZ dose, patients were randomly crossed over to the other two doses for 4 months each. Abbreviated Dyskinesia Rating Scale (ADRS) ratings were done weekly during naturalistic baseline, HLP, and the first CLZ dose phase. Thereafter, monthly ratings were done in the two subsequent crossover phases. Mean ADRS Total Scores were: BL= 23.2±5.4; HLP= 26.2±6.7; 100mg CLZ= 26.3±10.5; 300mg CLZ= 23.4±8.8; 600mg CLZ= 21.7±6.5. The Total ADRS scores at 600mg CLZ dose was significantly lower when compared to HLP (p<0.03) and 100mg CLZ (p<0.004). Patients were categorized at baseline into those “with TD” ( ) and “without TD” ( ) (Kane and Schooler criteria). Across the study phases patients “with TD”, did best on 600 mgCLZ. Mean ADRS Total Scores in those “with TD” were: BL= 26.4±4.3; HLP= 29.1±6.4; 100mgCLZ= 29.6±11.7; 300mg CLZ= 26.4±9.9 and 600mg CLZ= 23.7±7.4. This subgroup, when on 600mg CLZ differed significantly from BL (p<.03) and 100 mg CLZ (p<.008). Comparable findings were seen in the “extremities” and “facial & oral movements” sub-scales of the ADRS. Conversely, in the “without TD” subgroup, ADRS scores did not vary with dose. These data suggest that clozapine dose has an important influence on tardive dyskinesia.