Cohen-Mansfield J, Lipson S, Werner P, et al. Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: A controlled, double-blind study. Archives of Internal Medicine 1999;159:1733-40
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/10448776
Full text article: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1105636
| Methods | Study design: Randomized double-blind placebo-controlled crossover study
Number of groups: Two group. |
| Participants | Number of participants: 58 participants, 35 completed
Age: 86 years Sex: 43 female, 15 males Participants with dementia: Yes – mean MMSE was 7.90 Inclusion criteria: · Received either haloperidol, thioridazine or lorazepam for agitation · Residents of the facility so that nursing staff knew them well enough to assess them · Age 70 years and over Exclusion criteria: · Concomitant administration of other antipsychotic or anti-anxiety drug other than low-dose trazodone hydrochloride for sleep · Life expectancy less than 3 months due to obvious causes · Psychiatric diagnosis of a major affective disorder of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Third EditionRevised (DSM-IIIR) · Expected to leave the facility in the next 3 months · Uncontrolled hyperglycaemia · Uncontrolled hypoglycemia Country: United States of America Setting: Residential aged care facility |
| Interventions | Medicine: Typical antipsychotics and benzodiazepines
Withdrawal Schedule: Tapered during a 3-week periodthen ceased Comparator: Placebo compared to continued medicine. |
| Outcomes | Brief Psychiatric Rating Scale
Mansfield Agitation Inventory Function Adverse effects Global Impression Accuracy of staff prediction as to whether the withdrawal would be successful |
| Dates | Dates: Not described
Follow-up duration: 22 weeks. |
| Funding sources | National Institute on Aging, Bethesda, Md grants numbered AG00547 and AG10172 |
| Notes | Not clear which phase of the crossover the results are reported in so the data cannot be included in the meta-analysis. This information was sought, but not received. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | Method used to generate allocation sequence is not described.
“Half the residents were randomly assigned to have their medication dose tapered during a 3-week period, followed by receipt of a placebo (the other half continued their usual medication dosage).” |
| Allocation concealment (selection bias) | Unclear risk | No method of concealment was described. |
| Blinding of participants and personnel (performance bias) | Low risk | Study medications were given as identical liquids. Only the dispensing pharmacist knew which was administered. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Assessors were evening nursing staff and the unit’s social worker. We can assume that they remained blinded until after assessment, but this is unclear.
“Only the dispensing pharmacist, who was not an employee of the nursing home, knew which medication was administered. The care team, residents, family caregivers and research team were blinded to which group a participant was assigned.” |
| Incomplete outcome data (attrition bias) | Unclear risk | There was a high attrition rate. However, the reasons for drop-outs were similar across both groups and well described.
Twenty-three participants discontinued participation in the study before completion for the following reasons: death or dying (3), hospitalization (1), not eating or weight loss (3), increased agitation (9), lethargy (2), withdrawal of consent (4), facial asymmetry (1), and a fall (3); some had multiple reasons (Table 3). For 12 participants, discontinuation occurred during the original drug dosage, for nine while taking placebo, and for two during titration from drug to placebo. Most discontinuations (20 of 23) occurred in the first part of the study, before the crossover stage. All of these reasons could have been related to the intervention. Some analysis of demographics was undertaken between the drop-outs and those who completed the study. No differences were found. Unclear if an intention-to-treat analysis was used or not. |
| Selective reporting (reporting bias) | Low risk | Primary – Brief Psychiatric Rating Scale and Cohen-Mansfield Agitation Inventory Secondary – cognitive functioning, sleep, activity, positive mood, weight, adverse effects All outcomes were reported. |
| Other bias | Unclear risk | Funding and conflicts of interest were not reported. It is unlikely that these would have influenced the outcome.
Combining data from the deprescribing of two antipsychotics and one benzodiazepine may alter the results as these may have had different outcomes. |
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