Clark 1977.

Methods	Allocation: randomly assigned 'by sex' ‐ no further description. Blinding: double, identical capsules. Duration: 12 weeks (preceded by 8 week wash‐out). Design: parallel. Country: USA.
Participants	Diagnosis: schizophrenia (criteria not specified). History: 'chronic'. N=27. Sex: 13 M, 14 F. Age: mean 43.2 yrs, range 23‐61. Setting: hospital.
Interventions	1. Chlorpromazine: dose 1000 mg/day. N=9. 2. Placebo. N=9. 3. Butaclamol: dose 50 mg/day. N=9. Medication increasing to fixed dose; antiparkinson medication for EPS as required; sodium amytal and chloral hydrate for behaviour control as required.
Outcomes	Leaving study early. Global impression. CGI. Adverse effects. Unable to use ‐ Mental state: BPRS (no SD). Global impression: CGI (no SD). Behaviour: NOSIE (no SD). Physical tests: EKG, urine, blood (no data).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Allocation to treatment by sex was random" no further details reported.
Allocation concealment (selection bias)	Unclear risk	No information reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Placebo tablets identical to the white butaclamol and to the brown CPZ preparations were taken by all subjects during the dryout period and by the placebo group during treatment". "Each patient received his/her medication from individual stock bottles". "Double‐blind".
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"Double‐blind" no further details reported.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"Of the 27 subjects who started, three failed to complete the full 12 weeks of study: one female subject in the butaclamol group became excited and agitated during the 4th week of treatment, exacerbated a labile hypertension, and was dropped at the end of the 4th week as treatment failure. Two male subjects in the placebo group also manifested clinical deterioration, one at the 8th week and one at the 11th week of treatment, and were terminated as treatment failures. In each instance, final rating were obtained and their data were retained in the analysis". Last observation carried forward method used.
Selective reporting (reporting bias)	High risk	No SDs reported for BPRS, CGI and NOSIE, and no data reported for physical tests.
Other bias	High risk	Supported in part by a USPHS grant and a grant‐in‐aid from Ayerst Laboratories, NY.