Aripiprazole 2017.

Study characteristics
Methods	Randomisation: randomised, no further details. Allocation: procedure not described. Blinding: double‐blind, no further details. Duration: terminated early after 37 events (pre‐planned), mean duration of treatment was 164,5 days. Design: parallel. Location: multi‐centre. Setting: outpatients.
Participants	Diagnosis: adolescent patients (13 to 17 years old) with schizophrenia (DSM‐IV‐TR) stabilised on aripiprazole for 7 to 21 weeks before entering the double‐blind phase. N = 146. Gender: 96 men, 50 women. Age: mean 15,4 years (range 13 to 17 years). History: duration stable‐ at least 7 weeks (clinical judgment and rating scale defined), remission at baseline‐ n.i., duration ill‐ 2.1 years, number of previous hospitalisations‐ n.i., age at onset‐ 13.3 years, severity of illness‐ mean PANSS total score 64,6, mean CGI‐S total score 3,1, baseline antipsychotic dose‐n.i.
Interventions	1. Drug: aripiprazole. Flexible dose. Allowed dose range: 10 mg/day to 30 mg/day. Mean dose: 19,2 mg/day. N = 98. 2. Placebo: inert placebo. Duration of taper: n.i. N = 48. Rescue medication: not allowed.
Outcomes	Examined Relapse: rating scale based and/or need for hospitalisation and/or clinical judgment. Leaving the study early (any reason, adverse events, inefficacy). Global state‐ number of patients in symptomatic remission (Andreasen criteria, LOCF endpoint cross‐sectional criteria) Global state‐ number of patients in sustained remission (Andreasen criteria, maintained for 6 months) Social functioning: Children´s Global Assessment Scale Adverse events Death. Suicidal ideation: Columbia Suicide Severity Rating Scale. Unable to use/Not included Global state ‐ number of participants improved (no usable data). Mental state: PANSS total score and subscores (no predefined outcome of interest). Quality of life: Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (no usable data).
Notes	Sponsored by Otzuka Pharmaceutical Development and Commercialization. Adolescent patients subgroup.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised (2:1 ratio), no further details.
Allocation concealment (selection bias)	Unclear risk	Procedure not described.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blind, no further details.
Blinding (performance bias and detection bias) Subjective outcomes	Unclear risk	Double‐blind, no further details.
Blinding (performance bias and detection bias) Objective outcomes	Low risk	Double‐blind, no further details.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The overall attrition rate of 33% could still be acceptable, though higher than 25%, but more participants in the placebo group left the study early, mostly due to relapse. This difference may have biased the results of outcomes other than leaving the study early and relapse, which was assessed using the Kaplan‐Meier survival curve analysis. Data for secondary outcomes were both analysed on an ITT basis (LOCF method) and provided for completers at several time points.
Selective reporting (reporting bias)	Low risk	The primary outcome relapse was reported as prespecified; Efficacy and Safety: Quality of Life score not reported completely, but it is not a primary outcome.
Other bias	High risk	Terminated early (after 37 relapse events), but it was pre‐planned.