Sakurai 2016.

Methods	Randomisation: randomised to 1 of the 2 treatment groups in a 1:1 ratio by simple randomisation stratified by their antipsychotic type and treatment setting; computer‐generated randomisation list. Blinding: double; identical powder form in amount and color; participants blinded to their allocated intervention; assessors blinded to the allocation. Duration: 4 weeks Design: parallel Location: single‐centre (Japan) Setting: inpatients and outpatients
Participants	Diagnosis: schizophrenia, schizoaffective or persistent delusional disorder (ICD‐10) N = 103 Gender: 38 men, 65 women Age: mean 50.7 years (SD = 15.81) History: duration of illness ‒ mean 16.05 years (SD = 14.4); total duration of antipsychotic treatment‐ mean 10.9 years (SD = 14).
Interventions	All participants had been receiving olanzapine 10 mg/day or risperidone 3 mg/day for at least 4 weeks. Participants who had a total score ≥ 60 on the PANSS, ≥ 3 on the CGI‐S, and ≤ 70 on the GAF were considered non‐responders and were randomised to either: 1. dose increase: olanzapine 20 mg/day or risperidone 6 mg/day (double antipsychotic dose). N = 52; or 2. dose maintenance: olanzapine 10 mg/day or risperidone 3 mg/day. N = 51.
Outcomes	Global state: clinically relevant response (defined as ≥ 25% PANSS total score reduction) Leaving the study early (due to adverse events, any reason and inefficacy) Mental state: general (PANSS total score), positive symptoms (PANSS positive subscore), negative symptoms (PANSS negative subscore) Global state (CGI‐I) Functioning: overall (GAF) Adverse effects (EPS ‐ SAS, Akathisia ‐ BAS, tardive dyskinesia ‐ AIMS) Unable to use: Global state: CGI‐S (no mean, no SD) Plasma concentrations, not a protocol outcome
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "...randomly allocated to 1 of the 2 treatment groups in a 1:1 ratio by simple randomization stratified by their antipsychotic type (ie, olanzapine or risperidone) and treatment setting (ie, inpatient or outpatient)....according to a computer‐generated randomization list..." (pg. 1382).
Allocation concealment (selection bias)	Low risk	Quote: "The person who was independent of this study in the central office prepared a piece of paper on which 1 of the assigned groups was designated according to a computer‐generated randomization list, inserted it into an envelope on which a participant ID number was written, and sealed it. Upon registration of each participant, 1 of the investigators opened the envelope that corresponded to the participant's ID, and the person who prepared the envelopes confirmed that the envelopes were appropriately opened." (pg. 1382).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "During the 4‐week observation, all antipsychotic drugs were provided in identical powder form in amount and color with lactose added... Thus, the participants were blinded to their allocated intervention." (pg. 1382).
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The following assessments were performed by assessors who were blinded to the allocation..." (pg. 1383).
Incomplete outcome data (attrition bias) All outcomes	Low risk	Significantly more participants in the dose increase group (30.8%) than in the dose continuation group (13.7%) left the study early due to side effects. Reasons for leaving the study early were described. An ITT approach was used. Results between ITT analysis and only competers were similar.
Selective reporting (reporting bias)	High risk	CGI‐S was used but scores at endpoint were not available
Other bias	Low risk	No obvious risk for other bias

Scales

AIMS: Abnormal Involuntary Movement Score BAS: Barnes Akathisia Scale

BARS: Behavioral Activity Rating Scale

BAS: Barnes Akathisia Rating Scale

BPRS: Brief Psychiatric Rating Scale

CDRS: Calgary Depression Rating Scale

CGI‐I: Clinical Global impression‐Improvement

CGI‐S: Clinical Global impression‐Severity

CPRS: Comprehensive Psychopathological Rating Scale

GAF: Global Assessment of Functioning

HQLS: Heinrichs‐Carpenter‐Hanlon Quality of Life Scale

NOSIE: Nurse's Observation Scale for Inpatient Evaluation

PANSS: Positive and Negative Syndrome Scale for Schizophrenia

RGS: Roering Global Scale

SAFE: Social‐Adaptive Functioning Evaluation

SANS: Scale for the Assessment of Negative Symptoms

SAS: Simpson Angus Scale

SCoRS: Schizophrenia Cognition Rating Scale

SOFAS: Social and Occupational Functioning Scale

Diagnostic Tools

DSM: Diagnostic and Statistical Manual of Mental Disorders

ICD: International Classification of Diseases

RDC: Research Diagnostic Criteria for schizophrenia or schizoaffective disorders

Others

BMI: Body‐mass‐index

ECG: Electrocardiogram

EPS: Extrapyramidal Symptoms

ITT: Intention‐to‐treat

LOCF: Last observation carried forward

mg: Milligram

msec: Millisecond

N: Number

n.i.: Not indicated

SD: Standard deviation