Breitbart 1996.

Methods	Randomised clinical trial, single‐site, double‐blind, parallel groups, dose‐titrated Study duration: unclear but at least 7 days Location: USA
Participants	Total: 244 patients consented to participation and were monitored prospectively for the development of delirium. 30 patients became delirious and were randomised. Setting: hospital Mean age years (SD): 39.2 years (SD = 8.8) Gender no. (%): 23 male (77%), 7 female (23%) Diagnosis (%): all patients had AIDS Delirium severity: baseline delirium severity was assessed by the Delirium Rating Scale (DRS). Mean scores were: 20.45 (SD = 3.45) in the haloperidol arm; 20.62 (SD = 3.88) in the chlorpromazine arm; and 18.33 (SD = 2.58) in the lorazepam arm Performance status: mean Karnofsky Performance Status (KPS) across all participants was 52.3 (SD = 21.3, range: 10 to 90), with no difference across treatment groups. KPS scores range from 0 (dead) to 100 (normal). Inclusion criteria: patients with AIDS, ability to consent, medically stable, met DSM‐III‐R criteria for delirium, score of 13 or greater on the DRS Exclusion criteria: hypersensitivity to neuroleptics or benzodiazepines; presence of neuroleptic malignant syndrome; concurrent treatment with neuroleptic drugs; seizure disorder; current systemic chemotherapy for Kaposi's sarcoma; withdrawal syndrome or anticholinergic delirium for which a more specific treatment was indicated; diagnosis of schizophrenia; schizoaffective disorder or bipolar disorder; patients in whom delirium appeared to be part of a terminal event (i.e. patient was expected to die within 24 hours)
Interventions	Intervention 1: haloperidol; mean dose during the first 24 hours: 2.8 mg (SD 2.4), average maintenance dose from day 2 to end of treatment 1.4 mg (SD 1.2), n = 11 Intervention 2: chlorpromazine; mean doses during the first 24 hours: 50 mg (SD 23.1), average maintenance dose from day 2 to end of treatment 36 mg (SD 18.4), n = 13 Intervention 3: lorazepam; mean doses during the first 24 hours: 3 mg (SD 4.7), average maintenance dose from day 2 to end of treatment 4.6 mg (SD 4.7), n = 6 Assessment every hour in first 24 hours until participant was stabilised (calm, sleeping and not delirious). Lorazepam arm stopped midway through study early due to adverse effects Timing of treatment: each participant was evaluated hourly in first 24 hours with the DRS and the Extrapyramindal Rating Scale. At the end of each hour, if the participant's score was still 13 or greater on the DRS, the next level dose was administered. After stabilization, a maintenance dose was started on day 2, and continued for up to 6 days of treatment protocol Treatment duration: 7 days
Outcomes	Outcomes (primary and secondary outcomes undifferentiated): Delirium symptoms assessed by the DRS Change in cognitive status assessed by the Mini‐Mental State scores Extrapyramidal effects assessed by the Extrapyramidal Symptom Rating Scale ‒ a subjective questionnaire relating to parkinsonian symptoms Other adverse effects, assessed by the Side effects and Symptoms Checklist
Notes	Funded by the National Institute of Mental Health grant MH‐45664. No information on conflicts of interest provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients meeting criteria for delirium were randomised by the hospital pharmacy and treated in a double‐blind fashion with one of the three study drugs". Comment: no information provided on how patients were randomised
Allocation concealment (selection bias)	Low risk	Randomised by hospital pharmacy
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "double blinded" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information on extent of missing data or how it was handled. No information on which scores were averaged to obtain average delirium rating scale scores on day 2. In all trial arms participants died during treatment (2 chlorpromazine, 2 haloperidol, 1 lorazepam). Lorazepam arm terminated early due to adverse effects but results presented alongside those of the other trial arms.
Selective reporting (reporting bias)	Unclear risk	Protocol not available. Insufficient information to judge selective reporting bias.
Sample size	High risk	Fewer than 50 participants per arm