Bergh S, Selbaek G, Engedal K. Discontinuation of antidepressants in people with dementia and neuropsychiatric symptoms (DESEP study): double blind, randomised, parallel group, placebo controlled trial. British Medical Journal 2012;344(e1566):12-12
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/22408266
Full text article: https://www.bmj.com/content/344/bmj.e1566.long
| Methods | Study design: Randomized double-blind controlled study with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 128 randomized, 117 completed
· Intervention deprescribing group: 63 randomized, 59 completed · Control group: 65 randomized, 58 completed Age: 85.3 ± 8.2 Sex: 96 female, 32 male Participants with dementia: All participants Inclusion criteria: · Dementia (Alzheimer’s Disease, vascular dementia or a mixture of Alzheimer’s disease and vascular dementia) defined by the ICD-10 · Residents in an aged care facility for four or more weeks · Neuropsychiatric symptom(s) · Prescribed a selective serotonin reuptake inhibitor for at least three months Exclusion Criteria: · History of a depressive disorder or schizophrenia · Severe somaticdisease or terminal illness · Inability to take tablets or capsules as prescribed Country: Norway Setting: Residential aged care (52 sites) |
| Interventions | Medicine: Antidepressants
Withdrawal schedule: Not described Comparator: Placebo compared to continued medicine |
| Outcomes | Cornell scale
NeuropsychiatricIndex Quality of life-Alzheimer’s disease scale Unified Parkinson’s disease rating scale Severe impairment battery Lawton and Brody’s physical self-maintenancescale Weight Change in number of psychotropic drugs taken Oxazepam (mg)/day in last 21 days Change in number of falls per day in the last 21 days Clinical dementia rating Death |
| Dates | Dates: August 2008 to June 2010
Follow-up duration: 25 weeks |
| Funding sources | Innlandet Hospital Trust, the Research Council of Norway and the South-Eastern Norway Regional Health Authority |
| Notes |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Low risk | Individually randomized and across sites.
“We used computer-generated randomization (1:1) in blocks of four…. Randomization was done acrossstudy centers and facilities.” |
| Allocation concealment (selection bias) | Low risk | “Packing of study treatment was done at the Hospital Pharmacy at the Innlandet Hospital Trust, and was kept hidden, by the use of blank labels, from the participants, caregivers, and the assessors until the completion of data collection and statistical analyzes.” |
| Blinding of participants and personnel (performance bias) | Low risk | “Encapsulated tablets for the remaining three antidepressants and correspondingplacebo capsules containing only inert filler.”
“Packing of study treatment was done at the Hospital Pharmacy at the Innlandet Hospital Trust, and was kept hidden, by the use of blank labels, from the participants, caregivers, and the assessors until the completion of data collection and statistical analyzes.” |
| Blinding of outcome assessment (detection bias) | Low risk | As above |
| Incomplete outcome data (attrition bias) | High risk | It appears that the aim was to use an intention-to-treat analysis,but the actual tables report “as-treated.”
“Forty-seven (37%) patients withdrew from the study prematurely, 28 (44%) in the discontinuation group and 19 (29%) in the continuation group. The only reason for drop-outs that differed significantly between groups was an increase in neuropsychiatric symptoms, for 13 (21%) patients in the discontinuation group and four (6%) in the continuation group.” |
| Selective reporting (reporting bias) | Low risk | No pre-published protocol found, but the specified outcomes are reported.
Cornell scale for depression in dementia Neuropsychiatric inventory after 25 weeks Unified Parkinson’s disease rating scale Quality of life-Alzheimer’s Disease scale Lawton and Brody’s physical self-maintenancescale Severe impairment battery score Clinical dementia rating scale |
| Other bias | High risk | The study excluded participants with a history of depression. Considering that depressive disorders Selective Serotonin Reuptake Inhibitors (SSRIs) are a valid and common indication for prescribing an SSRI, this seems to exclude a substantial cohort.
The grouping of “neuropsychiatric symptoms” together is a major weakness. Although schizophrenia was an exclusion criterion, the neuropsychiatric inventory includes many common psychotic symptoms that can be caused by many illnesses besides depression. |
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