Devanand DP, Pelton GH, Cunqueiro K, et al. A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer’s disease. International Journal of Geriatric Psychiatry 2011;26:937-43.
PubMed link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685500/
Full text article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685500/pdf/nihms475451.pdf
| Methods | Study design: Randomized double-blind placebo-controlled study with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 44 randomized for treatment phase, 20 randomized for deprescribing phase
· Active deprescribing group: 10 randomized, 10 completed · Control group: 10 randomized, 10 completed Age: 75.0 ± 8.0 years Sex: 25 female, 19 male Participants with dementia: All, baseline withdrawal: · MMSE: 12.3 (6.3) · Brief Psychiatric Rating Scale total: 19.0 (2.7) Inclusion criteria: · Age 50–95 years · Clinical diagnoses of dementia by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-IV) criteria and probable Alzheimer’s Disease by National Institute of Neurological and Communicative Disorders and Stroke Alzheimer’s Disease and Related Disorders Association criteria based on history, physical examination,and structural brain imaging · Folstein MMSE permitted range was 5–26 · Current symptoms of psychosis or agitation Exclusion criteria: · Acute unstable medical condition · Delirium · Alcohol or substance abuse or dependence during the prior year · Clinical evidence of stroke · Other dementias including vascular or Lewy body or frontotemporal dementia · Multiple sclerosis · Parkinson’sdisease · Huntington’sdisease · Tardive dyskinesia · Diagnosis of a psychotic disorder antedating the onset of dementia · Antipsychotic medication usage during the 4 weeks before study entry · Contraindication to the use of haloperidol |
| Interventions | Medicine: Haloperidol – mean (SD) dose of haloperidol: 1.58 (SD 1.0) mg/day
Withdrawal schedule: Patients on 4 mg daily at the end of the haloperidol treatment phase: · Week 1: 2 mg daily · Week 2: 1 mg daily · Week 3: Placebo Patients on 2 or 3 mg daily at the end of the haloperidol treatment phase: · Week 1 & 2: 1 mg daily · Week 3: Placebo Patients on 0.5 mg or 1 mg at the end of the haloperidol treatment phase: · Week 1: Directly to placebo without a tapering period Comparator: Placebo compared to continued treatment Country: United States of America Setting: Community – a Memory Disorders Clinic or an affiliated Behavioral Neurology practice group |
| Outcomes | Relapse measured by Clinical Global Impression-ChangeBehavior measured by MMSEModified Blessed Functional Activity ScaleDeath Brief Psychiatric Rating Scale Unified Parkinson’s Disease Rating Scale |
| Dates | Dates: Not described
Follow-up duration: 44 weeks – 20 weeks treatment phase, 24 weeks deprescribing phase |
| Funding sources | National Institute of Health grants R01MH55735 and R01 AG17761 |
| Notes | The authorsstated: “Dr. Devanand has received grants from the National Institutes of Health, research support from Novartis and Eli Lilly, and has served as a consultant to GlaxoSmithKline (GSK), Bristol-Myers Squibb, and Sanofi-Aventis. Dr. Pelton has received research support from GSK, Novartis, and Forest and has served as a consultant to Bristol-MyersSquibb and Pfizer. Dr. Sackeim has received grants from the National Institutes of Health and served as a consultant to MECTA, Cyberonics, and Neuronetics. Dr. Marder has received grants from the National Institutes of Health, the Parkinson Disease Foundation and research support from Amarin Neuroscience LTD, Boehringer-Ingelheim, and Neurosearch.” |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | Subjects were stated to be randomized,but the randomizationmethod was not described. |
| Allocation concealment (selection bias) | Unclear risk | The detail was insufficient to ascertain risk of selection bias. Although identical capsules were used to hide placebos, we cannot tell if the allocation was concealed. |
| Blinding of participants and personnel (performance bias) | Unclear risk | Haloperidol and placebo were made up in identical-looking opaque white capsules. No data is given to be able to assess personnel or assessor blinding |
| Blinding of outcome assessment (detection bias) | Unclear risk | As above |
| Incomplete outcome data (attrition bias) | High risk | Incomplete data were well reportedincluding “All data from these patients were included in the intent-to-treat, last observation carried forward, analyzes.” |
| Selective reporting (reporting bias) | Low risk | The criteria used well-established rating scales. Failure was measured as relapse. Criteria for relapse were minimum 50% worsening from the sum score of three target symptoms at end Phase A, a sum score ≥ 6 on these 3 items (range 0–18), and minimal or greater worsening on the Clinical Global Impression-Change score (rated for psychosis/agitation). Criteria for relapse needed to be met at only a single time point during Phase B. There was no reporting of the scale measurements for Phase B – only the overall relapse figures were given. |
| Other bias | Low risk | Sound methodology. Both authors had significant disclosures to make having received grants and research support from drug companies. The riskof bias here is unlikely to have made any difference as the measurement scales are robust and the end-point was clear-cut. |
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