Itoh 1969.

Methods	Allocation: randomised. Blindness: double. Duration: 8 weeks, preceded by one week wash‐out. Setting: multi‐centre, Japan.
Participants	Diagnosis: schizophrenia. N = 80. Age: mean ˜ 34 years. Sex: 18 F, 62 M. History: inpatient; duration of illness ranged from less than 12 months (6%) to over 10 years (33%). Included: showing one or more of the following: state of intense excitement; stuporous state; pronounced hallucinations and/ or delusions; pronounced delusions; markedly devoid of spontaneity and apathetic (fresh or subacute hebephrenia; or chronic, terminal deteriorative state); pronounced neurosis‐like state. Excluded: no details. Consent: not stated.
Interventions	1. Perphenazine: (oral, 4 mg) + lactose; initially 45 mg daily, increased to 90 mg within one week, then individual dosage according to symptoms and adverse events, n = 40. 2. Clothiapine: (oral, 15 mg); initially 12mg daily, increased to 24 mg within one week, then individual dosage according to symptoms and adverse events, n = 40.
Outcomes	Leaving the study early. Global state: no better or worse. Behaviour: no better or worse. Adverse events. Unable to use ‐ Mental state: Psychiatric Rating Scale (unpublished scale).
Notes	Antiparkinsonism drugs and hypnotic agents were prepared and used when deemed necessary by the clinician.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised: randomisation by numbers, quote: "patients with the same type of disorder, clinical features and sex and with differences in ages of less than ten years were paired among those examined by the same physicians at each institution, and the data obtained were analysed by the sequential trial technique of Armitage upon conclusion of the study period. After the code had been broken, the pairs were untied and the data evaluated for testing for the therapeutic efficacy of the two drugs" (p7). Random number table used (p8).
Allocation concealment (selection bias)	Low risk	Quote, "bottles were coded so that neither the investigators nor the patients knew whether clothiapine or placebo was being administered at any given time, [and] every investigator was instructed to retain an allocation schedule in a sealed envelope for each matched pair assigned to him in case of medical emergency of a patient under study" (p8) ‐ no such emergency happened and all envelopes were returned unopened to the central statistical unit upon completion of the study.
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind: identical shape and colour of tablets. Quote, "medication and analysis of data obtained were performed by the controlled double‐blind method" (p8).
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No details.
Selective reporting (reporting bias)	Unclear risk	None detected.
Other bias	Unclear risk	Funding: not stated. Raters: not stated to be independent of treatment.