Kane 2002*.
Methods | Allocation: random.
Blinding: double.
Duration: 12 weeks (preceded by up to 4 mg risperidone/day for 1 week).
Design: parallel. Setting: inpatient and outpatient, multi‐centre (41 centres in the USA). |
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Participants | Diagnosis: schizophrenia (DSM‐IV).
N = 400.
Age: 18 to 55 years of age; mean˜37 ± 20 years.
Sex: 301 M, 99 F.
History: diagnosis of schizophrenia. Included: baselines PANSS of 60 to 120; good general health; standard laboratory test results 'within reference ranges or not clinically significant'. Excluded: received depot in past 120 days before start of trial; substance dependant diagnosis; tardive dyskinesia; history of neuroleptic malignant syndrome; clinically significant ECG abnormality; pregnant (or likely to become pregnant) or lactating; at risk of violent behaviour; current suicide ideation; history of severe drug sensitivity/ allergy (sensitivity to risperidone); people who were unresponsive to risperidone. Consent: trial conducted in accordance with 'current ICH‐Good Clinical Practice guidelines and the Declaration of Helsinki and its subsequent revisions'; written informed consent obtained from each participant or guardian/ legal representative. |
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Interventions | 1. Risperidone depot: 25 mg 2 weekly + 2 mg/day oral risperidone for 3/52, n = 99. 2. Risperidone depot: 50 mg 2 weekly + 4 mg/day oral risperidone for 3/52, n = 100. 3. Risperidone depot: 75 mg 2 weekly + 6 mg/day oral risperidone for 3/52, n = 100. 4. Placebo injections: 2 weekly + placebo tablets for first 3/52, n = 100. | |
Outcomes | Adverse events: ESRS and others as reported by participants. Leaving the study early. Unable to use ‐ Global state: CGI. Mental state: 20% reduction PANSS. Body weight: change. Pain at injection site. Physiological tests: including ECG. Mental state: change PANSS (no SD). |
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Notes | ||
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Randomised: quote, "a dynamic method (22) was used to randomly assign patients to treatment groups. Stratification factors included investigator, inpatient/outpatient status, and Positive and Negative Syndrome Scale (23) total score at randomization." |
Allocation concealment (selection bias) | Unclear risk | No details of allocation concealment. |
Blinding (performance bias and detection bias) All outcomes | Unclear risk | "Double blind study" but not clear who exactly was blinded, no indication given of whether the raters were blinded. Study controlled with "placebo injections that were identical in appearance [to the study drug injections]". |
Incomplete outcome data (attrition bias) All outcomes | High risk | Greater than 50% attrition by study end. |
Selective reporting (reporting bias) | Unclear risk | Unclear risk |
Other bias | High risk | Funding: "supported by Johnson & Johnson Pharmaceutical Research and development, Titusville, N.J." |