Marjerrison 1964.

Methods	Allocation: random.                                                                               Blinding: double. Duration: 7 months, two phases: (i) 5 months; (ii) 2 months. Design: parallel (4 groups); single centre. Setting: inpatient, Saskatchewan Hospital, North Battleford (Canada).
Participants	Diagnosis: n = 76 schizophrenia (remaining n = 12 with other ‘chronic psychotic’ diagnosis)1. N = 88 *(n = 50 included in the analysis ‐ see interventions). Age: mean 48 years. Sex: 38M, 40F *(21M, 23F included in the analysis ‐ 6M, 7F trifluoperazine; 15M, 16F placebo). Ethnicity: not stated. Consent: not stated. History: mean length of illness – placebo: 20 years; trifluoperazine: 13 years. Mean length of current hospitalisation ‐ placebo: 19 years; trifluoperazine: 13 years. All participants had received phenothiazines continuously for at least one year. Included: ‘highly treatment‐resistive’; long‐term inpatients from two male and two female continued‐treatment wards. Excluded: history of epileptic seizures; those receiving ‘psychotic energizers’ (anti‐depressive compounds); those who were considered likely candidates for imminent discharge.
Interventions	1. Trifluoperazine: 10 mg capsules, n = 16. i) phase 1:  mean dose 2.9 capsules = 29 mg; ii) phase 2: mean dose 2.7 capsules = 27 mg. 2. Placebo: n = 34. i) phase 1: mean = 4.1 capsules; ii) phase 2: mean = 5.7 capsules.2 *(3. Usual phenothiazine: varying doses determined clinically in both phase 1 and 2, n = 30 ‐ this group was not included in the analysis). *(4. Chlorprothixene: 50 mg capsules, n = 8 ‐ this group was not included in the analysis: i) phase 1:  mean dose 4.0 capsules = 200 mg; ii) phase 2: mean dose 5.4 capsules = 270 mg).
Outcomes	Leaving the study early: any reason; due to adverse effects. Adverse effects: dermatosis; seizure. Behaviour: use of adjunctive medication for sedation (barbiturate). Extrapyramidal adverse effects: use of anti‐Parkinson drugs. Unable to use ‐ Global and mental state: clinical worsening in one patient in each the trifluoperazine and placebo group ‐ no usable data. Behaviour: PRP ‐ no means or SD.
Notes	1The n = 12 of mixed diagnosis were, quote, “evenly distributed among the groups” (p293). 2Anti‐Parkinsonian drugs used 'when necessary' (p292). Where a participants' behaviour were not adequately controlled by a higher‐dose of either treatment prescription, barbiturate sedatives were permitted for use alongside study medication.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised ‐ randomly assigned ‐ no further details.
Allocation concealment (selection bias)	Unclear risk	No description.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double – participants kept on their original wards throughout study duration, in order to enable "continuity of observation by the behaviour‐rating nurses in charge" (p291) in addition to other psychosocial treatments continued 'as usual'; no changes to recreational leave or discharge policy for the study population. Drugs given in individually‐assigned colour‐coded bottles with variations of dosage determined by clinical staff, with doses administered in a "multiplicity of forms" to minimise observer bias towards a particular prescribed drug (p292). Large effort described to keep patients and study personal blinded. However, 16/31 patients in the placebo group phase II were given 'no medication' whilst 15/31 were given a 'second placebo', implying no blinding of half the placebo group in phase II.
Incomplete outcome data (attrition bias) All outcomes	High risk	Follow‐up: 89% ‐ n = 10 participants left the study early. From the trifluoperazine group: n = 1 was dropped due to 'clinical worsening', n = 1 was transferred to another hospital for administrative reasons, and n = 1 was discontinued due to adverse reaction (dermatosis). From the placebo group: n = 2 were dropped due to 'marked worsening' and n = 1 left due to 'idiopathic seizures'. From the usual phenothiazine group: n = 3 were dropped due to 'clinical worsening', and n = 1 was dropped due to improvement leading to ward transfer for discharge planning (p294). No ITT used in the trial, but used for meta‐analysis.
Selective reporting (reporting bias)	Unclear risk	No means or SD reported for scales.
Other bias	Unclear risk	Funding: trifluoperazine and chlorprothixene supplied by Smith, Kline and French; Montreal and Hoffman LaRoche. Rating scales: raters independent of treatment.