Casey 2009.
| Methods | Allocation: randomised Blinding: double Duration: 12 weeks (preceded by wash‐out period: 1‐5 days) Design: parallel Country: USA |
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| Participants | Diagnosis: current DSM‐IV‐TR diagnosis of schizophrenia, confirmed by a Structured Clinical Interview for DSM‐IV‐TR (SCID)* n = 402 Sex: 304 M, 89 F***. Age: 18 – 65 years (mean: 40.0 ± 10.52 years)** History: mean age of first diagnosis 24.2 ± 8.3 years Setting: multi‐centre, people with schizophrenia hospitalised for a minimum of 14 d during the acute phase of the study and could be discharged (per investigator discretion) anytime after day 14 |
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| Interventions | 1. Olanzapine + placebo: fixed dose of olanzapine, mean dose = 15 mg/d; n = 103 2. Olanzapine + divalproex ER: fixed dose of olanzapine, mean dose = 15 mg/d; mean dose of divalproex ER = 2828 mg with a flexible dose not exceeding 35 mg/d; n = 99 3. Risperidone + placebo: fixed dose of risperidone, mean dose = 6 mg/d; n = 101 4. Risperidone + divalproex ER: fixed dose of risperidone, mean dose = 6 mg/day, mean dose of divalproex ER = 2712 mg with a flexible dose not exceeding 35 mg/day; n = 99 Co‐medication: lorazepam, propranolol hydrochloride, and benztropine mesylate could be used as adjunctive medications, but were not to be used prophylactically |
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| Outcomes | Leaving the study early: acceptability/tolerability of treatment Clinical response: global state (CGI severity and improvement scales), mental state (PANSS total, BPRS total), positive symptoms, negative symptoms, general pathology (PANSS subscales) Unable to use: Adverse events: EPS, SAS, BAS, and AIMS (no data) |
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| Notes | * In the antipsychotic monotherapy group, 172 out of 198 participants (87%) were diagnosed as paranoid type. In the valproate group, 166 out of 195 participants (85%) were diagnosed as paranoid type ** Monotherapy: mean = 39.9 years (SD = 10.49 yrs). Combination: mean = 40.1 years (SD = 10.54 years) *** Monotherapy: 156 M, 42 F. Combination: 148 M, 47 F |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "randomized", no further details provided (p 1331) |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) Objective outcomes | Low risk | We don't think blinding causes significant bias in objective outcomes. |
| Blinding of participants and personnel (performance bias) Subjective outcomes | Low risk | "double‐blind" |
| Blinding of outcome assessment (detection bias) Objective outcomes | Low risk | We don't think blinding causes significant bias in objective outcomes. |
| Blinding of outcome assessment (detection bias) Subjective outcomes | Unclear risk | "raters completed a rater‐training program", no further details provided (p 1331) |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Used technique of LOCF but reported data for people leaving the study early very high (62%) (p 1332) |
| Selective reporting (reporting bias) | High risk | No data reported for extrapyramidal symptoms, measured by SAS, BAS and AIMS |
| Other bias | Low risk | No obvious other bias |