Methods	Allocation: random, no further details. Blindness: double, no further details. Duration: 8 weeks. Design: parallel. Location: multicentre.
Participants	Diagnosis: (DSM-IV) schizophrenia, PANSS of 60 or more, CGI-S of 4 or more. N = 673. Sex: 510 M, 163 F. Age: 18-65 years (mean quetiapine = 40.2 years, mean risperidone = 39.6 years). History: duration ill, age at onset: not reported. Setting: in- and outpatient, initially inpatient.
Interventions	Quetiapine:flexible dose. Allowed dose range: 200-800 mg/day. Mean dose: 525 mg/day. N = 338. Risperidone: flexible dose. Allowed dose range: 2-8 mg/day. Mean dose: 5.2 mg/day. N = 335
Outcomes	Leaving the study early: any reason, adverse events, inefficacy. Global State: CGI. Mental State: PANSS total score, PANSS positive subscore, PANSS negative subscore. Adverse effects: open interviews, cardiac effects (QTc), death (natural causes, suicide), EPS (akathisia, dystonia, parkinsonism, use of antiparkinson medication, AIMS, BAS, SAS), sedation, prolactin associated side effects (dysmenorrhoea, galactorrhea, sexual dysfunction) weight gain, laboratory (cholesterol, glucose, prolactin, 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 both 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	High risk	The overall attrition was high (52.1%). 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. Data on study completers were also available. Nevertheless it is unclear whether any statistical method can account for such a degree of attrition
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 quetiapine.