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
a
Plasma levels should be taken after 5 days of unchanged clozapine dosing and 12 hours from last clozapine dose.
b
A 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
c
A 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