Ballard C, Thomas A, Fossey J, et al. A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: The neuropsychiatric inventory median cutoff is a predictor of clinical outcome. Journal of Clinical Psychiatry 2004;65:114-19.
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/14744180
Full text article: https://www.psychiatrist.com/JCP/article/Pages/2004/v65n01/v65n0120.aspx
| Methods | Study design: Randomized double-blind, placebo-controlled study with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 100 randomized, 72 completed
· Intervention deprescribing group: 46 randomized, 32 completed · Control group: 54 randomized, 40 completed Age: 83.6 ± 9.3 years Sex: 81 female, 19 male Participants with dementia: all · Median MMSE: 3.0 (range 0 – 21.0) · Clinical Dementia Rating scale, score, N (%) o Stage 1: 4 (8.7) o Stage 2: 15 (32.6) o Stage 3: 27 (58.7) · Neuropsychiatric Index totalscore: median 16.0 (range 0–35.0) · Agitation factor: median 4 (range 0–16) · Psychosis factor: median 0 (range 0–16) · Mood factor: median 16.0 (range 0–35.0) · Well-being score: median 2.35 (range 0.26–6.40) Inclusion criteria: · 65 years and over · Met National Institute of Neurological and Communicative Diseases and Stroke/ Alzheimer’s Disease and Related Disorders Association criteria for probable or possible Alzheimer’s Disease · Clinical Dementia Rating scale severity of stage one or greater · No severe behavioralsymptoms on individual symptom scores over seven on the Neuropsychiatric Inventory at the time of evaluation Exclusion criteria: · None described Country: England Setting: Residential aged care facilities in two centers – Newcastle and Oxford, United Kingdom |
| Interventions | Medicine: Antipsychotics
· Atypical antipsychotics (risperidone) · Typical antipsychotics (thioridazine, haloperidol, trifluoperazine, chlorpromazine) Withdrawal Schedule: Not described Comparator: Placebo compared to continued medicine |
| Outcomes | Quality of life (measured as differences in change in behavioralsymptoms)
Change in Neuropsychiatric Inventory |
| Dates | Study dates: June 2000 to June 2002
Follow-upduration: Three months |
| Funding sources | Research intoAging (London, UK) |
| Notes |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | The method of allocation was not described.
“Subjects were then randomized to neuroleptic (N = 54) or placebo (N = 46).” |
| Allocation concealment (selection bias) | Unclear risk | Allocation concealment method was not described. |
| Blinding of participants and personnel (performance bias) | Low risk | Independent company used to encapsulate over the medications. Dispensing was done by pharmacies at the centers.Scripts were writtenbefore randomization.
“The study was conducted using a double-blinddesign. All study neuroleptics were encapsulated by an independent company to maintain blind, and dispensing was coordinated by the pharmacy departments at the two centers. Prescriptions were written beforerandomization in a twice-daily regimen, allocating to each participant the closest dose to their pre-existing prescription from the doses encapsulated.” |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors is unclear. The center coordinator was blind, but it was not clear if this person was the outcome assessor.
“…the centercoordinator, blinded to neuroleptic status…” |
| Incomplete outcome data (attrition bias) | Low risk | “All evaluations were undertaken at baseline. The Neuropsychiatric Index and Dementia Care Mapping assessments were also completed at 1- and 3-month follow-up. Study withdrawals and the proportion of people developing marked behavioralsymptoms are described and compared between groups using the chi-square test.””Fourteen patients (26% active treatment, 30% placebo) withdrew from the study in each group (χ2 = 0.25, p =.62). There were only six withdrawals in the placebo- treated group (13%) and five withdrawals in the active treatment group (9%) because of behavioral deterioration (χ2 = 0.36, p =.55). Other withdrawals were because of:· physical health problems (active N = 3 [6%], placebo N=2 [4%]) · death (active N=3[6%], placebo N=3 [7%]) · protocol violation (active N = 2 [4%], placebo N = 1 [2%]) · withdrawal of consent (active N = 3 [6%], placebo N = 2 [4%])
Eighty-two (82%) of the patients completed at least one follow-up evaluation and were included in the primary outcome analysis.” “For all participants who completed at least one follow-up assessment, the last evaluation was carried forward.” |
| Selective reporting (reporting bias) | Low risk | There was no pre-specified protocol available, but the outcomes in the paper match the described objectives. |
| Other bias | Unclear risk | Unclear what method of recruitment was used. |
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