Methods	Allocation: random, no further details. Blindness: double, no further details. Duration: 12 weeks. Design: parallel. Location: multicenter.
Participants	Diagnosis: (DSM-IV) schizophrenia disorganised (n = 46), catatonic (n = 4), paranoid (n = 140), residual (n = 15) or undifferentiated (n = 51) of intent to treat population, poor previous treatment response, CGI of 4 or more, BPRS of 45 or more. N = 273. Sex: 182 M, 74 F (of intent-to-treat population, n = 256). Age: 18-65 years (mean clozapine = 37.8, mean risperidone = 39.5) (of intent-to-treat population). History: duration ill mean clozapine = 13.0 years, mean risperidone = 15.5 years (of intent-to-treat population), age at onset: not reported. Setting: in- and outpatient.
Interventions	Clozapine: flexible dose. Allowed dose range: 200-900 mg/day. Mean dose: 642 mg/day. N = 138. Risperidone: flexible dose. Allowed dose range: 2-15 mg/day. Mean dose: 9 mg/day. N= 135
Outcomes	Leaving the study early: any reason, adverse events, inefficacy. Global State: CGI. Mental State: PANSS total score, BPRS total score, PANSS positive subscore, PANSS negative subscore, Calgary depression scale, psychotic depression scale, psychotic anxiety scale. Adverse effects: open interviews, death, EPS, sedation, seizures, constipation, hypotension, sialorrhoea, tachycardia, agitation, anxiety, insomnia, nausea, headache, fatigue, fever, weight gain, laboratory (white blood cell count)
Notes
Risk of bias
Bias	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear risk	Random, no further details.
Allocation concealment?	Unclear risk	No further details.
Blinding? subjective outcomes	Unclear risk	Double, no further details. Whether blinding was successful has not been examined, but the compounds differ quite substantially in side effects. This can be a problem for blinding
Blinding? objective outcomes	Low risk	Objective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding
Incomplete outcome data addressed? All outcomes	Unclear risk	The overall attrition was moderate (26.7%) . The LOCF method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change of his condition if he had remained in the study. This assumption can obviously be wrong. It is unclear whether this led to bias
Free of selective reporting?	High risk	Only those adverse events that occurred in at least 5% of the participants were reported. This procedure can miss rare, but important adverse events
Free of other bias?	High risk	The study was sponsored by the manufacturer of clozapine.