Kramer 1975.

Methods	Allocation: randomly assigned by block ‐ no further description. Blindness: double ‐ identical capsules. Duration: 4 weeks. Design: parallel. Country: USA. Setting: hospital.
Participants	Diagnosis: acute schizophrenia (presence of clinical symptoms according to BPRS). n = 90. Age: range 18 to 54 years, mean ˜ 33 years. Sex: 70 men, 20 women. History: newly admitted to hospital. Excluded: history of brain, cardiovascular, hepatic or renal disorders; history of alcoholism or drug addiction; mental retardation; history or clinical evidence of glaucoma.
Interventions	1. Metiapine: range 25 mg/day to 600 mg/day, mean 219 mg/day. n = 30.* 2. Chlorpromazine: range 50 mg/day to 1200 mg/day, mean 427 mg/day. n = 30. 3. Combination of butabarbital + atropine: between butabarbital sodium 225 mg/day + atropine sulphate 0.26 mg/day and butabarbital sodium 180 mg/day + atropine sulphate 2.04 mg/day. Mean butabarbital sodium 78 mg/day + atropine sulphate 1.17 mg/day. n = 30.
Outcomes	Global state: clinical improvement (CGI), nurse's evaluation (change score NOSIE). Adverse effects: movement disorders, hepatic problems, 'severe reactions', cardiovascular problems. Leaving the study early. Unable to use: Mental state: BPRS (no SD).
Notes	* Only 5 of the metiapine participants, 1 of chlorpromazine participants and 1 of the butabarbital + atropine participants received maximal dosage.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "recently hospitalized schizophrenics who were randomized into three groups." "Patients were assigned in blocks of six, with two patients being assigned to each of the three groups."
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "a four‐week double‐blind study."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data were addressed in the study. Full‐analysis‐set, used to assess efficacy measures. All‐participants‐treated‐set, used to assess safety measures.
Selective reporting (reporting bias)	Unclear risk	All expected outcomes reported, some means and SDs omitted.
Other bias	Unclear risk	Metiapine supplied by Merrell‐National Laboratories. No source of funding reported.