Clozapine resistant schizophrenia: Newer avenues of management

Table 1 Key components of the current definitions of clozapine-resistant schizophrenia[12,14-16]

Diagnosis	Diagnosis of schizophrenia using standardized criteria and after ruling out psychosis due to substance use or medical conditions
Adequate clozapine treatment
Dose	200-500 mg/d
Blood levels	≥ 350 ng/mL
Treatment duration	2-3 mo1
Treatment adherence	≥ 80% of prescribed doses for the duration of treatment
Response to clozapine
Baseline symptom severity and functional impairment	Moderately severe illness either globally or in positive and negative symptom domains assessed using standardized scales (CGI, BPRS, PANSS, SAPS, SANS). Moderate levels of functional impairment assessed using standardized scales (GAF, SOFAS)
Non-response	< 20% reduction in symptoms and minimal response in levels of functional impairment during an adequate trial of clozapine treatment
Persistence	Moderately severe illness and functional impairment should persist following an adequate trial of clozapine treatment

¹It has been proposed that duration of clozapine trials should be 2 mo for patients with aggression or self-harm, 3 mo for those with positive symptoms, and 4 mo for those with negative and cognitive symptoms[13].

BPRS: Brief Psychiatric Rating Scale; CGI: Clinical Global Impression scale; GAF: Global Assessment of Functioning scale; PANSS: Positive and Negative Syndrome Scale; SANS: Scale for the Assessment of Negative Symptoms; SAPS: Scale for the Assessment of Positive Symptoms; SOFAS: Social and Occupational Functioning Scale.