Devanand DP, Mintzer J, Schultz SK, et al. Relapse Risk after Discontinuation of Risperidone in Alzheimer’s Disease. New England Journal of Medicine 2012;367:1497-507
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/23075176
| Methods | Study design: Randomized double-blind placebo-controlled study with a parallel-design
Number of groups: Three groups |
| Participants | Number of participants: 110 randomized, 34 completed
· Active deprescribing (16 weeks treatment, 32 weeks placebo) group: 40 enrolled, 13 completed · Active deprescribing (32 weeks treatment, 16 weeks placebo) group: 38 enrolled, 14 completed · Control (48 weeks treatment) group: 32 enrolled, 10 completed Age: 80.3 ± 7.7 years Sex: 66 female, 44 male Participants with dementia: All Inclusion criteria: · Outpatients or residents of assisted-living facilities or nursing homes · 50 to 95 years of age · Met criteria for dementia of the DSM-IV, and the criteria for probable Alzheimer’s Disease of the National Institute of Neurological and Communicative Disorders and Stroke Alzheimer’s Disease and Related Disorders Association · Neuropsychiatric Index score of four or more at both screening and baseline on the delusions or hallucinations sub-scale, or the agitation–aggression sub-scale · MMSE score of five to 26 in the case of outpatients OR two to 26 in the case of nursing home residents Exclusion criteria: · History of stroke · Transient Ischemic Attack · Uncontrolled atrial fibrillation Country: United States of America Setting: Community and residential aged care facilities – approximately half the participants lived in the community and half in assisted-living facilities or residential care. Patients were recruited from memory clinics (including Alzheimer’s research centers), geriatric psychiatry clinics, and clinics at Veterans Affairs medical centers, as well as through physician referrals and advertising. |
| Interventions | Medicine: Risperidone
Withdrawal Schedule: Not described Comparator: · 48 weeks treatment compared to · 32 weeks treatment and 16 weeks placebo compared to · 16 weeks treatment and 32 weeks placebo |
| Outcomes | Adverse events
Relapse Simpson–Angus Scale Abnormal Involuntary Movement Scale Treatment Emergent Symptoms Scale Alzheimer’s Disease Assessment Scale – cognitive Physical Self-Maintenance Scale MMSE scores Increases in body weight |
| Dates | Dates: Not described
Follow-up duration: 48 weeks total |
| Funding sources | National Institutes of Health (R01 AG021488 and R01 AG17761) and the Department of Veterans Affairs |
| Notes |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Low risk | The study statistician prepared a randomized permuted-blocks procedure, with blocks of 3 or 6, to balance the group assignment in each of four (2 × 2) strata.
Stratification within each site was according to: · Presence or absence of psychosis at baseline · Residence (assisted-living facility or nursing home vs. home). |
| Allocation concealment (selection bias) | Low risk | The central pharmacy of the New York State Psychiatric Institute maintained the assignment code, and clinicians and raters remained unaware of the group assignments of all patients during the entire study |
| Blinding of participants and personnel (performance bias) | Low risk | The central pharmacy of the New York State Psychiatric Institute maintained the assignment code, and clinicians and raters remained unaware of the group assignments of all patients during the entire study.
Immediately before the end of phase A, the pharmacy dispensed pre-packaged blister packs of risperidone or placebo tablets that were identical in appearance for patients eligible for randomization in phase B. |
| Blinding of outcome assessment (detection bias) | Low risk | As above |
| Incomplete outcome data (attrition bias) | Low risk | Patients who died and those in whom a relapse was considered to be imminent (as adjudicated by an independent research psychiatrist who was unaware of the group assignments) before they dropped out of phase B were classified in the analyzes as having had a relapse |
| Selective reporting (reporting bias) | Low risk | Reduction of 30% or more from baseline on the Neuropsychiatric Index score
Clinical Global Impression of Change For the secondary hypothesis, the end-point was the time to relapse during weeks 17 to 32 of phase B. |
| Other bias | High risk | Industry-sponsored |
Leave a Reply