Chan 2013.

Methods	Allocation: randomised. Design: multicentre, randomised, double‐blind, placebo‐controlled, double‐dummy, clinical trial. Duration: initially at 5 minutes followed by at 10, 30 and 60 minutes. Settings: trial undertaken in 3 large metropolitan EDs.
Participants	Diagnosis: people with agitation or aggression. N = 227. Age: 18 to 65 years. Sex: not specified. History: highly agitated people aged 18 to 65 years, requiring parenteral drug sedation for acute agitation, as determined by a registrar (senior resident) or consultant emergency physician. Excluded: people with known hypersensitivity or contraindication to midazolam, droperidol or olanzapine; obvious reversible cause for agitation (e.g. hypotension, hypoxia, hypoglycaemia); known pregnancy; acute alcohol withdrawal; received (within the previous 12 hours) oral or parenteral sedative drug(s) either as usual or out‐of‐hospital acute agitation treatment.
Interventions	1. Droperidol 5 mg IV + placebo‐olanzapine. N = 112. 2. Olanzapine 5 mg IV + placebo‐droperidol. N = 109. 3. Control group: placebo‐droperidol, placebo‐olanzapine. N = 115.
Outcomes	Global state: time to achieve adequate sedation for first time, need for additional parenteral sedative drugs, need for repeat sedation within 60 minutes of initial sedation, total midazolam dose administered in the 60 minutes after initial adequate sedation and from 60 minutes after initial adequate sedation until ED discharge, proportion adequately sedated at 5 and 10 minutes after study drug administration. Service use: ED length of stay. Adverse effects: corrected QT interval (QTc), need for airway management or assisted ventilation, oxygen desaturation (90%). Physiological: systolic blood pressure < 90 mmHg, dystonic reactions, seizures, vomiting or aspiration, and movement disorders.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Computerized block randomisation (blocks of 6), stratified by study site, was performed by an independent pharmacist". Response: randomisation probably done.
Allocation concealment (selection bias)	Low risk	Quote: "After enrolment, patients were assigned to the next study pack in the allocated sequence". Response: low risk of selection bias.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "All patients, ED staff, and study personnel remained blinded to group allocation until data entry and analyses were completed". Response: low risk of performance bias.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "The appearance of the drug vials and the dosage instructions for the placebo and active study drugs were identical". Response: low risk of detection bias.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Of 457 patients screened for eligibility, 121 were excluded and 336 were enrolled. All groups had similar baseline characteristics. Patients with minor protocol violations (mainly delays in initial midazolam administration) were included in the analysis. The nature of the violations did not differ substantially between the groups". Response: incomplete outcome data addressed.
Selective reporting (reporting bias)	Low risk	All the outcomes were adequately reported.