Breitbart 1996.

Methods	Design: randomised, three‐arm trial Blinding: double‐blind Duration: duration was not specified. Authors reported the outcomes respectively based on the time of baseline, day two and end of treatment. Setting: St Luke's/ Roosevelt Hospital Center, New York, USA
Participants	Diagnosis: adult patients who met the case definition for AIDS of the Centers for Disease Control and were undergoing treatment for acquired immune deficiency syndrome (AIDS)‐related medical problems N = 30. Age: mean 39.2 years old (range 23 to 56). Sex: 7 female, 23 male. Race/ethnicity: 17 black, 8 Hispanic, 4 white, 1 Asian. Inclusion criteria: medically hospitalised patients diagnosed with AIDS and who met DSM‐III‐R criteria for delirium scoring 13 or greater on the Delirium Rating Scale (DRS) Exclusion criteria: included known hypersensitivity to neuroleptics or benzodiazepines; presence of neuroleptic malignant syndrome; concurrent treatment with neuroleptic malignant syndrome; concurrent treatment with neuroleptic drugs; seizure disorder; concurrent systemic chemotherapy for Kaposi's sarcoma; withdrawal syndrome of anticholinergic delirium for which a more specific treatment was indicated; current or past diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder; patients in whom delirium appeared to be part of a terminal event
Interventions	1. Lorazepam (n = 6)*: initial dose was lorazepam 0.50 mg/hour for oral and 0.20 mg/hour for intramuscular. Mean drug dose administered during the first 24 hours of treatment was lorazepam 3.0 mg. Average maintenance dosage was lorazepam 4.6 mg. Note: that this arm of the trial was terminated half‐way through due to 'treatment limiting' adverse events, and all remaining participants in this arm were randomised to either chlorpromazine or haloperidol. 2. Chlorpromazine (n = 13): initial dose was chlorpromazine 10 mg/hour for oral and 5 mg/hour for intramuscular. Mean drug dose administered during the first 24 hours of treatment was chlorpromazine 50.0 mg. Average maintenance dosage was chlorpromazine 36 mg. 3. Haloperidol (n = 11): initial dose was haloperidol 0.25 mg/hour for oral and 0.125 mg/hour for intramuscular. Mean drug dose administered during the first 24 hours of treatment was haloperidol 2.8 mg. Average maintenance dosage was haloperidol 1.4 mg. *Each participant with delirium was evaluated hourly with the DRS and the Extrapyramidal Symptom Rating Scale (ESRS). If the patient's score on the DRS was still 13 or greater, the next level dose of study drug was administered. If the patient was asleep, calm, and not hallucinating or had scored 12 or below on the DRS, a maintenance dose was started on day two, and the maintenance dose was equal to one half of the first 24‐hour dose requirement, given in a twice a day regimen.
Outcomes	Severity of delirium measured by DRS (a 10‐item scale integrating DSM‐III criteria designed to be used by clinicians to identify delirium in the medically ill; items are rated on a Likert‐type scale of 0 to 3 (absent ‐ mild ‐ moderate ‐ severe)); Mortality from all causes; Extrapyramidal side effects (measured using Extrapyramidal Symptom Rating Scale, ESRS) — unable to use (not predefined in this review protocol); Cognitive status measured by the Mini‐Mental State (a score of 28 to 30 was rated as 0 (no deficits) on item 6 of the Delirium Rating Scale, a score of 25 to 28 was rated as 1 (very mild deficits), a score of 20 to 24 was rated as 2 (focal deficits), a score of 15 to 19 was rated as 3 (significant deficits), and a score of 15 or less was rated as 4 (severe deficits)); Early termination/side effects (symptom checklist)
Notes	Enrolment: quote: "patients were enrolled onto the study when they became delirious and met criteria for treatment in the protocol during the 28‐month data collection period." Consent: quote: "since informed consent could not ethically be obtained from subjects once delirium had developed, we devised a prospective research strategy in which only medically stable patients who had the capacity to give informed consent were recruited. While many patients exhibited clinical evidence of AIDS‐related dementia, only those who lacked the capacity to give informed consent were not approached." *When we performed the analyses, we created separate comparisons to compare lorazepam with each of the other controls (chlorpromazine, haloperidol).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients meeting criteria for delirium treatment were randomised by the hospital pharmacy and treated in a double‐blind fashion with one of the three study drugs." The paper mentioned "randomly assigned", but there was a lack of description about the randomisation method.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not described.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote "in a double‐blind fashion", but no further information
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote "in a double‐blind fashion", but no further information
Incomplete outcome data (attrition bias) All outcomes	High risk	Five participants (two in the haloperidol group ‐ 2/11, 18.1%; two in the chlorpromazine group ‐ 2/13, 15.4%; and one in the lorazepam group ‐ 1/6, 16.7%) lost to follow‐up because they died within eight days of initiation of the protocol.
Selective reporting (reporting bias)	Low risk	Results were reported for all stated outcomes.
Other bias	High risk	Quote "Midway through the study, it became apparent that all the patients who received one of the study drugs developed treatment‐limiting adverse side effects. Consistent with hospital policy, the study pharmacist determined which drug had been used to treat these patients. All of these patients had been treated with lorazepam. Lonazepam was removed from the study at that point. All subsequent patients were treated with the two remaining study drugs in a randomized, double‐blind procedure." The randomisation procedure changed midway through the study. Funding: The trial was supported by NIMH grant MH‐45664. The paper reported that "some of the authors of this publication are also working on these related projects: meaning‐centred group psychotherapy for cancer survivors". Declarations of interest: authors did not provide information regarding conflict of interest.