Prien 1969*.

Methods	Allocation: random.                                                                             Blinding: double. Duration: 24 weeks, 4 week observation period pre‐trial. Setting: inpatient, 6 hospitals ‐ Broughton State Hospital, NC, Dorothea Dix State Hospital, NC, Kentucky State Hospital, KY, Manhattan State Hospital, NY, St. Louis Hospital, MO, Springfield State Hospital, MD (USA). Design: parallel (3 groups), single centre.
Participants	Diagnosis: chronic schizophrenia. N = 3411. Age: 18‐55 (mean age 41.8 years, 60% were 45+ years old). Sex: 180M, 180F (30M, 30F from each hospital). Ethnicity: not stated. History: chronic schizophrenics with length of hospitalisation 2‐33 years with mean 15 years. 55% of patients were hospitalised 10+ years. Inclusion: a primary diagnosis of schizophrenia, age between 18‐55, continuous hospitalisation for at least 2 years. Exclusion: organic brain disease, mental deficiency or medical conditions that would otherwise put the patient at increased risk when taking high dose drugs. Consent: not stated.
Interventions	1. Trifluoperazine: (high dose) 80 mg/day, gradual increase from previous dose to 80 mg/day after 35 days, n = 117. 2. Trifluoperazine: (low dose) 15 mg/day, n = 113. 3. Placebo: n = 111.
Outcomes	Global state: clinical improvement (defined a 'markedly improved' using the Doctor's Global Improvement Scale) ‐ together and by high dose and low dose. Extrapyramidal adverse effects: akathisia; Parkinsonian reaction; dystonia ‐ together and by high dose and low dose. 2Other adverse effects: specific ‐ seizures; hypotension; dizziness; fainting; nausea/vomiting; skin rashes; photosensitivity; insomnia; drowsiness; decreased appetite ‐ together and by high dose and low dose. Leaving the study early: any reason; due to severe adverse effects; due to relapse or worsening ‐ together and by high dose and low dose. Unable to use: Mental state: BPRS; IMPS ‐ no usable data. Behaviour: NOSIE ‐ no usable data. Hospital and service utilisation outcomes: follow‐up ‐ discharge ‐ not enough data.
Notes	1Study paper reads: "approximately 60 chronic schizophrenics...were selected at each hospital [and] each treatment group consisted of approximately 120 patients" (p54). No concrete data were found for true participant numbers; however, we used the data available to us that represented n = 117 in high‐dose trifluoperazine; n = 113 in low‐dose trifluoperazine; and n = 111 in placebo groups (N = 341). 2All adverse effect data and numbers leaving the study early were calculated from percentages. High and low doses were combined as well as reported separately versus placebo.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised ‐ quote, "patients were randomly assigned to one of three groups” (p306).
Allocation concealment (selection bias)	Unclear risk	No description.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double ‐ “all medication was administered in capsule form under double‐blind conditions for 24 weeks” (p306).
Incomplete outcome data (attrition bias) All outcomes	High risk	Where the study only gives an approximation as to the original number of randomised participants (N = 360), it is hard to identify the true number of participants that dropped out or that were included in the final analysis.
Selective reporting (reporting bias)	Unclear risk	No data provided for IMPS, BPRS, NOSIE, Global Improvement Scale, or Discharge‐Readiness Inventory (DRI).
Other bias	Unclear risk	Funding: Public Health Service grants: MH‐10292, MH‐10332, MH‐11384, MH‐10989, MH‐11046, MH‐11047 and contract SA‐43‐ph‐3064 all from the National Institute of Mental Health. Rating Scales: scales were administered by the research physician; unclear whether they were independent of treatment.