Clozapine Dose for Schizophrenia

Summary

A Cochrane review [Abstract] 1 included 5 studies with a total of 452 participants with schizophrenia. Each compared the effects of clozapine at very low dose (up to 149 mg/day), low dose (150 mg/day to 300 mg/day) and standard dose (301 mg/day to 600 mg/day). The study lengths varied from 6 to 16 weeks.

• Very low dose compared to low dose:There was no evidence of effect on mental state between low and very low doses of clozapine in terms of average Brief Psychiatric Rating Scale-Anchored (BPRS-A) endpoint score (MD 3.55, 95% CI −4.50 to 11.60; 1 RCT, n = 31). One short-term study (6 weeks, n = 59) found no difference between groups in body mass index (BMI) (MD −0.10, 95% CI −0.95 to 0.75), but serum triglycerides were lower at low-dose (MD 1.00, 95% CI 0.51 to 1.49).
• Very low dose compared to standard dose:There was no evidence of effect on mental state between very low doses and standard doses in terms of average BPRS-A endpoint score (MD 6.67, 95% CI −2.09 to 15.43; 1 RCT, n = 31). One study (n=58) found no difference between groups in BMI in the short term (MD 0.10, 95% CI −0.76 to 0.96).Weight gain was lower at very low dose (MD −2.70, 95% CI −5.38 to −0.02; 1 RCT, n = 27). In one trial (n=58) glucose level one hour after meal was also lower at very low dose (MD −1.60, 95% CI −2.90 to −0.30) but total cholesterol levels higher compared to standard dose (MD 1.00, 95% CI 0.20 to 1.80).
• Low dose compared to standard dose:There was no evidence of effect on mental state between the doses in terms of both clinician-assessed clinical improvement (RR 0.76, 95% CI 0.36 to 1.61; 2 RCTs, n = 141) and clinically important response as more than 30% change in BPRS score (RR 0.93, 95% CI 0.78 to 1.10; 1 RCT, n = 176). One study (n = 57) found no difference between groups in BMI in the short term (MD 0.20, 95% CI −0.84 to 1.24).There were fewer adverse effects, measured as lower TESS scores, in the low-dose group in the short term (MD −3.99, 95% CI −5.75 to −2.24; 2 RCTs, n = 266). In one study (n=176) the incidence of lethargy (RR 0.77, 95% CI 0.60 to 0.97), hypersalivation (RR 0.70, 95% CI 0.57 to 0.84), dizziness (RR 0.56, 95% CI 0.39 to 0.81) and tachycardia (RR 0.57, 95% CI 0.45 to 0.71) was lower at a low dose.