Gwynne 1962.

Methods	Allocation: random.                                                                Blinding: double. Duration: 4 months. Design: parallel (3 groups), single centre. Setting: inpatient, closed wards, Athens State Hospital, Columbus, Ohio (USA).
Participants	Diagnosis: schizophrenia (including hebephrenic; catatonic; paranoid; chronic undifferentiated). N = 78 *(n = 52 included in the analysis ‐ see interventions). Age: < 60, mean age 49 years. Sex: 39M, 39F *(26M, 26F included in the analysis ‐ x3 groups, with 13M and 13F in each). Ethnicity: not stated. Consent: not stated. History: average time in hospital of 20 years; all participants had previously responded poorly to somatic therapy; no other type of therapy given for at least one month; none of the participants had received trifluoperazine before. Included: diagnosis of schizophrenia for a period of 5 years or more; a history of withdrawal for one year or more. Excluded: not stated.
Interventions	1.Trifluoperazine: week one: 5 mg twice daily (total 10 mg/day); week two: 10 mg twice daily (total 20 mg/day); week three: 15 mg twice daily (total 30 mg/day); after this time, 20 mg twice daily (total 40 mg/day) until 'maximum improvement or side‐effects intervened', n = 26. 2. Placebo: twice daily, n = 26. *(3. Chlorpromazine: set dose schedule over a four‐week period, week 1: 50 mg twice daily (total 100 mg/day); week 2: 100 mg twice daily (total 200 mg/day); week 3: 150 mg twice daily (total 300 mg/day); after this time, 200 mg twice daily (total 400 mg/day) until 'maximum improvement or side‐effects intervened', n = 26 ‐ this group was not included in the analysis).1
Outcomes	Behaviour: agitation (undefined). Leaving the study early: any reason; due to adverse effects. Extrapyramidal adverse effects: general. Other adverse effects: general; specific ‐ difficulty swallowing; spasm muscles of mastication; drowsiness; blurred vision; anorexia; dermatitis; oedema of the face; incontinence of urine; fainting; convulsions. Unable to use ‐ Global state: The Lorr Multidimensional Scale for Rating Psychiatric Patients (MSRPP) – P values only. Need for additional medication: for side effects of study medication ‐ no usable data.
Notes	1Dosages were reduced when maximum improvement appeared to have been achieved. Where reduction of dosage resulted in exacerbation of symptoms, the dosage was again raised. Benztropine methanesulfonate was the only other drug administered to participants who developed adverse effects relating to the medication. This was done by initially lowering the dosage and adding 2 mg benztropine methanesulfonate daily.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised ‐ quote, "three groups of 26 patients… were formed by random selection” (p451).
Allocation concealment (selection bias)	Unclear risk	No description.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double (implied) ‐ "[A]ll drugs were identical in appearance and taste...[N]one of the evaluators had any knowledge of the drug groups and the code remained unbroken until the completion of the study” (p452‐3).
Incomplete outcome data (attrition bias) All outcomes	Low risk	n = 2/26 left in trifluoperazine and n = 1/26 in the placebo group due to severe EPS; a further n = 2 left the placebo group as they were judged by the investigator (not acting as an evaluator) to need 'active medication.' ITT used.
Selective reporting (reporting bias)	High risk	MSRPP scale was used; evaluations had different results; no means or SDs reported for outcome data.
Other bias	Unclear risk	Funding: Smith, Kline and French provided chlorpromazine and trifluoperazine; Merck, Sharp & Dohme provided benztropine. Rating scales: three independent evaluations for each participant were obtained from the ward attendants. In addition, two psychiatric residents independently evaluated each participant using the MSRPP. Other: quote, "a legitimate criticism of is that the five patient lost to the study before the first post‐medication evaluation should have been rated as failures. As far as bias is concerned the weighting is against the trifluoperazine group and in favour of the placebo, but the chlorpromazine group might have shown better advantage if the latter course had been taken" (p454).