Olanzapine 1999.

Study characteristics
Methods	Randomisation: randomly assigned (1:1), no further details. Allocation: procedure not described. Blinding: double‐blind, no further details. Duration: 3 to 5 days. Design: parallel (optional crossover treatment for relapsed patients). Location: multi‐centre. Setting: inpatients and outpatients (numbers not available).
Participants	Diagnosis: schizophrenia (DSM‐IV), received clozapine for a minimum of 4 weeks before entering the study, had to undergo an elective discontinuation of clozapine (49% due to patient inconvenience, 37% due to adverse events, 13% due to partial response). N = 106. Gender: 75 men, 31 women. Age: mean 38.8 years History: duration stable‐ received clozapine for at least 4 weeks before study entrance, duration ill‐ n.i., mean duration of antipsychotic treatment‐ range from 4 weeks to >1 year (4 weeks to 6 months: N = 39, 6months‐1year: N = 18, >1year: N = 59), number of previous hospitalizations‐ n.i., age at onset‐ n.i., severity of illness‐ mean PANSS total score 64.5 points, baseline antipsychotic dose‐ clozapine 324 mg/day (gradual tapering from baseline dose to 300 mg/day in 2 to 12 days).
Interventions	1. Drug: olanzapine. Fixed dose, 10 mg/day. N = 53. 2. Placebo: inert placebo. duration of taper 2 to 12 days. N = 53. Rescue medication: only benzodiazepines (for agitation) and anticholinergic (for evident EPS). Patients who relapsed could be removed from the double‐blind treatment and enter and optional open‐label cross‐over treatment (clozapine+olanzapine).
Outcomes	Examined Relapse: worsening on at least one of the following COSTART events: schizophrenic reaction, hallucinations, delusions, thinking abnormal. Leaving the study early (any reason, inefficacy) Unable to use/Not included Global state: CGI‐S mean change (no usable data). Mental state: PANSS (no predefined outcome of interest). Depressive symptoms: Montgomery Asberg Depression Rating Scale (no predefined outcome of interest). Performance tests: MiniMental State Examination (no predefined outcome of interest). Adverse events: no usable data. Suicidality: no usable data.
Notes	Not explicitly stated, probably sponsored (EliLilly)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomly assigned (1:1), 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 10% was acceptable, but more participants in the placebo group than in the olanzapine group left the study early due to inefficacy. This may be a source of bias for outcomes other than relapse and leaving the study early, but data on such other outcomes are not available. Analyses were all done on an ITT basis.
Selective reporting (reporting bias)	Low risk	No evidence for selective reporting.
Other bias	Unclear risk	Very short follow‐up (3 to 5 days, difficult to discriminate between withdrawal symptoms and illness recurrence); 13% of the randomised patients had partial response to clozapine.