Schiele 1961.
| Methods | Allocation: random. Blinding: double. Duration: 16 weeks (22‐week 'additional trial period'). Setting: inpatient, St Cloud, Minnesota (USA). Design: parallel (four groups), single centre. |
|
| Participants | Diagnosis: chronic schizophrenia. N = 80 *(n = 40 included in the analysis ‐ see interventions). Age: average 40.6 years. Sex: 80M. Ethnicity: not stated. History: participants were either "withdrawn or subject to periodic disturbances, and they were generally ineffective. All needed supervision and management" and most needed closed‐ward care. Average continuous hospitalisation for 10.0 years. Medication received prior to study included chlorpromazine (n = 30), mepazine (n = 35), trifluoperazine (n = 6), prochlorperazine (n = 2), various combinations (n = 7). Inclusion: diagnosis of schizophrenia; without history or evidence of complicating organic factors. Exclusion: age greater than 55 years; lobotomy. Consent: not stated. |
|
| Interventions | 1. Trifluoperazine: 5 mg capsules (10 to 50 mg/day), n = 20. 2. Placebo: n = 20. *(3. Chlorpromazine: 100 mg capsules (200 to 1000 mg/day), n = 20. *(4. Thioridazine: 100 mg capsules (200 to 1000 mg/day), n = 20. (Medication varied between 2 to 10 capsules a day given 2/4 times a day; anti‐Parkinsonian medication benztropine methanesulfonate used as needed to control EPS; phenobarbital used temporarily for sedation). |
|
| Outcomes | Global state: clinical improvement (defined as a global estimate of the amount of change in clinical condition using scores from the MBS and MMPI, including 'considerable improvement' and 'moderate improvement' ‐ judgement made by the investigators with the ward physician as chairman). Mental state: any clinically significant response in psychotic symptoms (defined as 'psychiatric condition becoming and remaining worse'). Hospital and service utilisation outcomes: discharge. Extrapyrimidal adverse effects: general side effects. Extrapyrimidal adverse effects: use of anti‐Parkinson drugs. Adverse effects: drowsiness; motor restlessness; rigidity; tremors; hypersalivation; slurred speech; incoordination; insomnia; skin disorder; fainting; blurred vision; lethargy; muscle weakness; tenseness; seizure; polydipsia and polyuria; decreased appetite. Leaving the study early: any reason; due to relapse or worsening. Unable to use ‐ Behaviour: MBS and MMPI ‐ no SD (adjusted means only). Improvement from 22‐week 'additional treatment period': blinding broken; only 71% participants from original sample. |
|
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Random ‐ no further description. |
| Allocation concealment (selection bias) | Unclear risk | No description. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Double ‐ quote, "strict double blind conditions...individual bottle of medication...capsules were identical in appearance..only hospital pharmacist had the code...". In the additional 22‐week trial period the double blind procedure was modified, these results were handled separately in the study. We have only used data from the first 16 weeks of the study. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Only 43 participants (n = 13 in the thioridazine group, and n = 10 from each of the other three groups) were tested at each specified point during the study using the MMPI, with the remainder of participants termed "untestable" (p155). |
| Selective reporting (reporting bias) | Unclear risk | No statistical data reported for the MMPI and MBS scales. |
| Other bias | Unclear risk | Funding: not stated. Rating scales: Manifest Behaviour Scale (MBS) completed twice on each participant by two nursing assistants working independently. Primary investigator was author of the MBS. Exclusion criteria: participants who had lobotomies, meeting the exclusion criteria, were "inadvertently included", with n = 2 in the thioridazine group and n = 1 chlorpromazine group. |
Rating scales
BPRS ‐ Brief Psychiatric Rating Scale BRS ‐ Beckombergo Rating Scale CGI ‐ Clinical Global Impressions Scale IMPS ‐ Inpatient Multidimensional Psychiatric Scale MMPI ‐ Minnesota Multiphasic Personality Inventory MSBS ‐ Minimal Social Behaviour Scale NOSIE ‐ Nurses' Observation Scale for Inpatient Evaluation PRP ‐ Psychotic Reactive Profile QPSS ‐ Quantification of Psychotic Symptom Severity TTB ‐ Tulane Test Battery WAIS ‐ Welchsler Adult Intelligence Scale
Other CNS ‐ central nervous system ECT ‐ electroconvulsive therapy EPS ‐ extrapyramidal symptoms IM ‐ intramuscular ITT ‐ intention‐to‐treat SD ‐ standard deviation tds ‐ three times daily