Paliperidone depot3M 2015.

Study characteristics
Methods	Randomisation: sponsor‐prepared computer‐generated randomisation scheme, balanced using permuted blocks across the treatment groups and stratified by study centre to ensure balance of treatment allocation within a centre. Allocation: interactive voice/web response system. Blinding: double‐blind, identical appearing capsules, administered by a person distinct from other study personnel. Duration: open‐ended after 66 weeks (longest patient), variable duration of the double‐blind phase (median: 158 days). Design: parallel. Location: multi‐centre (64 centres in 8 countries). Setting: outpatients.
Participants	Diagnosis: Schizophrenia (DSM‐IV‐TR), symptomatically stable when enrolled, then stabilised on paliperidone LAI for at least 12 weeks before randomisation. N = 305. Gender: 228 men, 77 women. Age: 37.8 years. History: duration stable‐ at least 12 weeks (duration of the open‐label maintenance phase), duration ill‐ 10.8 years, mean duration of hospitalisation‐ n.i., number of previous hospitalisations‐ n.i., age at onset‐ 26.9 years, severity of illness‐ mean PANSS total score 54.5, mean CGI‐S total score 2.7, baseline antipsychotic dose‐ paliperidone palmitate 3 months formulation 210 mg eq/3 months, remission at baseline‐ 53% of the participants were remitters at baseline.
Interventions	1. Drug: Paliperidone palmitate depot (3‐month formulation). N = 160 Fixed dose. Mean dose: 402 mg eq/3 months. Allowed dose range: 175 mg to 525 mg eq/3 months. 2. Placebo: duration of taper: depending on the elimination half‐life of paliperidone depot (between 84 and 139 days) N = 145. Rescue medication: anticholinergics (antiparkinson), beta‐blocker (akathisia), lorazepam (anxiety/agitation), zolpidem (sleep disturbances).
Outcomes	Examined Relapse (rating scale based and/or clinical judgement and/or need for hospitalisation or increase in the level of psychiatric care) Leaving the study early (any reason, inefficacy, adverse events). Social functioning: Personal and Social Performance Scale. Adverse effects (clinical judgement and rating scale based). Violent/aggressive behaviour. Death. Suicide ideation: Columbia Suicide Severity Rating scale based. Unable to use/Not included Global state ‐ number of participants improved (no usable data). Global state ‐ number of participants in remission (no usable data, only available for a subgroup of patients in remission at baseline, reported as change in remitter status, PANSS defined). Mental state: PANSS total score and subscores (no predefined outcomes of interest). Depressive symptoms: PANSS Marder factors (no predefined outcome of interest).
Notes	Sponsored by Janssen Research & Development, LLC.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sponsor‐prepared computer‐generated randomisation scheme, balanced using permuted blocks across the treatment groups and stratified by study centre to ensure balance of treatment allocation within a centre.
Allocation concealment (selection bias)	Low risk	Interactive voice/web response system.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, identical appearing capsules, administered by a person distinct from other study personnel.
Blinding (performance bias and detection bias) Subjective outcomes	Low risk	Double‐blind, identical appearing capsules, administered by a person distinct from other study personnel.
Blinding (performance bias and detection bias) Objective outcomes	Low risk	Double‐blind, identical appearing capsules, administered by a person distinct from other study personnel.
Incomplete outcome data (attrition bias) All outcomes	High risk	The overall attrition rate of 30% could still be acceptable, though higher than 25%, but three times as many participants in the placebo group left the study early 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 analysed on an ITT basis.
Selective reporting (reporting bias)	Low risk	No evidence for selective reporting. All the outcomes have been reported in the protocol‐specified way.
Other bias	High risk	Study terminated early after an interim analysis, but this was pre‐planned.