Table 2.

Comparison of published and proposed criteria for clozapine resistance in schizophrenia.

Published criteria	Mouaffak et al25	Proposed criteria for clozapine resistance
Adequate dose	Plasma levels > 350 ng/mL	Plasma levelsa ≥ 350 ng/mL for once a day dosing; ≥ 250 ng/mL for equal divided dosing, or oral dose ≥ 400 mg a dayb
Adequate duration, weeks	8	8, at adequate dosec
No significant improvement	<20% decrease on BPRS	CGI-SCH positive change > 2 (2 = much improved)
Current illness severity	BPRS ≥ 45, CGI-S ≥ 4, and ≥ 4 on at least 2 out of 4 positive items on the BPRS	CGI-SCH positive ≥ 4 (4 = moderately ill)
Duration of illness with no good functioning, years	5

BPRS = Brief Psychiatric Rating Scale; CGI-S = Clinical Global Impression–Severity; CGI-SCH = Clinical Global Impression–Schizophrenia.

^aPlasma levels should be taken after 5 days of unchanged clozapine dosing and 12 hours from last clozapine dose.

^bA daily clozapine dose of 400 mg has been shown to achieve a threshold of 350 ng/mL in various trials, and lies within the dose range advocated for by a field of experts for acute and maintenance treatment.^64–66

^cA study identified all clozapine responders within 8 weeks of a change in dose, indicating no increased benefits with continuing people on a particular dose longer to establish benefits.⁶⁷