Lorazepam 1997a, USA.

Study characteristics
Methods	Allocation: randomised. Blinding: double blind. Design: prospective, parallel, multi‐centre. Duration: 24 hours. Setting: emergency departments in 5 university/general hospitals in the US: University of Texas Southwestern Medical Center, Dallas; Harbor‐UCLA Medical Centre, Los Angeles; University of Nebraska Medical Center, Omaha; Albert Einstein Medical Centre, Philadelphia; and Harborview Medical Center, Seattle.
Participants	Diagnosis: schizophrenia (n = 47), psychosis (n = 27), psychoactive substance abuse (n = 16), mania (n = 13), schizophreniform disorder (n = 1). n = 98. Age: mean 34 years. Gender: 73 men, 25 women. Ethnicity: not stated. Consent: informed consent wherever possible. History: all participants exhibited psychosis and behavioural dyscontrol (agitated, aggressive, destructive, assaultive or restless behaviour). Inclusion: presentation to emergency department with psychosis and behavioural dyscontrol to the extent they were capable of harming themselves or others.  Score of ≥ 5 on ≥ 3 psychosis/anxiety items from the BPRS. Exclusion: obvious alcohol intoxication, central nervous system depression, allergic hypersensitivity, delirium, neuroleptic malignant syndrome, airway obstruction, severe hypotension or hypertension, acute narrow‐angle glaucoma, benzodiazepine or antipsychotic in previous 24 hours, fluphenazine decanoate in previous 2 weeks, haloperidol decanoate in previous 4 weeks, pregnancy.
Interventions	Benzodiazepine + antipsychotic vs benzodiazepine vs same antipsychotic. 1. Lorazepam 2 mg IM + haloperidol 5 mg IM, maximum 6 doses (n = 32). 2. Lorazepam 2 mg IM, maximum 6 doses (n = 31). 3. Haloperidol 5 mg IM, maximum 6 doses (n = 35). Administered over 12 hours with ≤ 6 doses. First 3 injections at least 1 hour apart and remainder 2 hours apart. Need for subsequent doses made by blinded evaluator. Most participants had < 3 doses (lorazepam: 74%; haloperidol: 71%; combination: 91%).
Outcomes	Global impression: no improvement*; need for additional medication; sedation. Behaviour: mean behaviour score (ABS). Mental state: mean endpoint score (BPRS psychosis subscale). Adverse effects/events: EPS; use of medication for EPS; ataxia, dizziness, dry mouth, speech disorder. Unable to use ‐ Global impression: CGI (no useable data).
Notes	*'Improvement' ‐ defined as a decrease of 1 from baseline or ≥ 2 from baseline on the CGI (at 3 hours). Sample numbers were not clear, as the authors stated that data were only collected if the participant was awake. Note: assumptions made regarding missing SDs data.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised ‐ eligible participants were "sequentially assigned using a computer‐generated table of random numbers to receive one of three therapies."
Allocation concealment (selection bias)	Unclear risk	Not stated.
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind ‐ "the emergency department psychiatrist who treated and rated the patient remained blinded to the identity of the patient's medication throughout treatment." Rating scales: administered by emergency department psychiatrist, who also treated the participant, but "remained blinded to the identity of the patient's medication throughout."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up: 100%. The data from 2 participants were excluded from the efficacy analysis, as it was later determined that they had both received prescribed antipsychotic medication shortly before entering the study. Unclear which group(s) these 2 participants were excluded from.
Selective reporting (reporting bias)	Low risk	All measure outcomes were reported.
Other bias	Unclear risk	Funding: supported in part by a grant from Wyeth‐Ayerst Research (now Pfizer). Unsure whether Pfizer were involved in study design and reporting process.