Hoyberg 1993.

Methods	Allocation: randomised. Blindness: double. Duration: 8 weeks, preceded by wash‐out ‐ no further details. Setting: multi‐centre.
Participants	Diagnosis: chronic schizophrenia disorder with acute exacerbation (DSM‐III‐R). N = 107. Age: 20 to 67 years, mean ˜ 36 years. Sex: 30 F, 77 M. History: chronic; outpatient; 93% of participants were receiving drugs of diverse categories pre‐wash‐out (most commonly‐used drugs included phenothiazines and thioxanthenes). Included: aged between 18 to 65; diagnosis of chronic schizophrenia with acute exacerbation (DSM‐III‐R); informed consent. Excluded: mental disorder other than chronic schizophrenic disorder; clinically significant organic disorders; clinically relevant abnormalities in laboratory tests; history of alcohol or drug abuse as defined in DSM‐III‐R within the 12‐month period preceding the study; reception of oral neuroleptic treatment less than 72 hours or depot neuroleptics less than 3 weeks before the start of treatment; commitment to a mental hospital; women of reproductive age without adequate contraception; pregnant or lactating women. Consent: informed consent required from participants or their relatives or legal guardians; study approved by relevant ethics committees in accordance with the Declaration of Helsinki II.
Interventions	1. Perphenazine: 8 mg per capsule, initially 2 capsules daily, dose could be changed during the first 4 weeks according to individual needs to a maximum of 48 mg/day, during the last 4 weeks dose was to be kept unchanged, but could be reduced if adverse events occurred*, n = 52. 2. Risperidone: 2.5 mg per capsule, initially 2 capsules daily, dose could be changed during the first 4 weeks according to individual needs to a maximum of 15 mg/day, during the last 4 weeks dose was to be kept unchanged, but could be reduced if adverse effects occurred*, n = 55.
Outcomes	Leaving the study early: any reason; due to adverse events. Global state: no better or worse (CGI). Mental state: PANSS (clinical improvement, defined as 'at least 20% reduction in total PANSS score at endpoint). Adverse events: UKU Side Effect Rating Scale Unable to use ‐ Mental state: BPRS; PANSS (no SD). Global state: CGI (no means or SD). Adverse events: ESRS (no SD).
Notes	*During the last 4 weeks dose was to be kept unchanged, but could be reduced if adverse effects occurred. **During the treatment period, n = 42 in the Risperidone group and n = 38 in the perphenazine group required concomitant medication (including benzodiazepines and orphenadrine).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised: no further details.
Allocation concealment (selection bias)	Unclear risk	Not stated.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Double‐blind: identical tablets.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Seventy‐eight participants (73%) completed the full 8‐week trial period; n = 29 withdrew prematurely, of these n = 8 receiving risperidone and n = 6 receiving perphenazine were withdrawn due to adverse effects; n = 2 receiving risperidone and n = 3 receiving perphenazine were withdrawn due to lack of therapeutic effect; n = 4 receiving risperidone and n = 6 receiving perphenazine were withdrawn because they stopped attending the control visits. All participants that had attended at least one clinical assessment were included in the ITT analysis or endpoint analysis (N = 101; n = 50 receiving risperidone and n = 51 receiving perphenazine). All prematurely withdrawn participants were included in side effects analysis, whereas other therapeutic measures were analysed ITT.
Selective reporting (reporting bias)	High risk	CGI scale reported as an outcome measure, however no data are reported.
Other bias	Unclear risk	Funding: not stated; two co‐authors had affiliations with Janssen Pharma, Denmark and Norway. Raters: not stated to be independent of treatment.