Reardon 1966.

Methods	Allocation: random.                                                                     Blinding: double. Duration: 4 ‐ 12 weeks. Setting: inpatient (USA). Design: parallel (3 groups), single centre.
Participants	Diagnosis: acute paranoid schizophrenia (Bleuler criteria). N = 34 *(n = 23 included in the analysis ‐ see interventions). Age: no data. Sex: 22M,12F ("number of males and females in each group were comparable"). Ethnicity: not stated. History: not stated. Included: those who demonstrated a thinking and affect disturbance, and who admitted the presence of persecutory delusions and hallucinations within 10 days prior to admission were selected. Exclusion: not stated. Consent: not stated.
Interventions	1. Trifluoperazine: 20 mg/day for first week, increased to 40 mg/day for the remainder of the study, n = 11. 2. Placebo: either 2 to 4 cc. or 5 to 10 cc 'as though it were one of the active drugs', n = 12. *(3. Chlorpromazine: 300 mg/day for first week, increased to 600 mg until completion of study, n = 11 ‐ this group was not included in the analysis). (IM barbiturates were administered 'on occasion' to deal with aggressive or assaultive behaviour).
Outcomes	Leaving the study early: any reason; due to adverse effects (relapse/ worsening ‐ ECT). Extrapyramindal adverse effects: Parkinsonism. Mental state: clinically significant response in positive symptoms (exhibited delusions and hallucinations); clinically significant response in psychotic symptoms (defined as exhibiting delusions and hallucinations). Hospital and service utilisation outcomes: hospital transfer/ home leave. Unable to use ‐ Global state and cognitive response: MMPI, Shipley Hartford and four sub tests of WAIS rating scores ‐ only P values given. Use of anti‐Parkinson drugs: Artane (10 mg) daily was given to all patients. No data and no Parkinsonian symptoms were observed. Behaviour: no usable data.
Notes	ITT used for outcomes not relating to adverse effects (leaving the study early and service utilisation outcomes only).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised ‐ the pharmacy controlled the allocation ‐ quote, “each subject was placed on a ward and randomly assigned trifluoperazine, chlorpromazine or placebo by the pharmacy” (p266) ‐ no further details.
Allocation concealment (selection bias)	Low risk	Allocation was controlled by the pharmacy; ward personnel and investigators did not know which drug each participant received. Participants were placed in active treatment wards in order to quote: "avoid the therapeutic milieu effect that might occur with placement on a special research unit" (p266).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double ‐ allocation was controlled by the pharmacy; ward personnel and investigators did not know which drug each participant received. Placebo administered quote: "as though it were one of the active drugs" (p266).
Incomplete outcome data (attrition bias) All outcomes	High risk	Follow‐up: 74%. Six participants were excluded from the investigation because they were given ECT (n = 2 receiving trifluoperazine; n = 1 receiving chlorpromazine; n = 3 receiving placebo) with an addition n = 3 (one from each group) removed from the study after transfer or home leave. Limited data provided and subjective clinical observations used.
Selective reporting (reporting bias)	Unclear risk	MMPI, Shipley Hartford WAIS ‐ no scale data or SDs reported.
Other bias	Unclear risk	Funding: Smith, Kline and French supplied the drugs and placebo. Rating scales: not clear whether nurses or other raters were independent of treatment.