Curran HV, Collins R, Fletcher S, et al. Older adults and withdrawal from benzodiazepine hypnotics in general practice: Effects on cognitive function, sleep, mood and quality of life. Psychological Medicine 2003;33:1223-37
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/14580077
Full text article: https://pdfs.semanticscholar.org/65de/e7256da861cf4ea29eeb468e78d8a9d11be4.pdf
| Methods | Study design: Randomized double-blind placebo-controlled study with a parallel-design
Number of groups: Three groups |
| Participants | Number of participants: 138 randomized, 104 completed
· Intervention deprescribing group: 104 randomized, 34 completed* · Intervention delayed deprescribing group: 21 randomized, 49 completed · Control group: 35 enrolled* Age: 77 ± 6.9 years (range 65 to 93 years) Sex: 98 female, 40 male Participants with dementia: No Inclusion criteria: · 65 years and over · Daily benzodiazepine use for at least 6 months · Identified from an audit of the 25 practices’ computer records Exclusion criteria: · Dementia · Organic states associated with cognitive dysfunction · History of seizures · Severe deafness · Severe visual impairment · Current major psychiatric disorders · Any patient that the general practitioner felt discontinuation was inappropriate Concomitant psychotropic medicine used: · Other daytime benzodiazepines (1 from group A, four from group C) · Antidepressants (4 patients in group A, two in group B, three in group C) Country: England Setting: Community – 25 general practices in inner city and suburban London, as well as rural areas. These areas were all parts of the teaching and research network of the Royal Free and UCL Medical School. |
| Interventions | Medicine: benzodiazepines
· Temazepam (mostly 10mg) – 69%, 69%, 48% respectively across the three groups · Nitrazepam (mostly 5mg) – 24%, 29%, 47% respectively across the three groups · Alprazolam (mostly 1mg) – 7%, 4%, 5% respectively across the three groups Withdrawal Schedule: A dose titration regime was devised to minimize the risk of withdrawal symptoms. This was done according to each patient’s original dose and particular benzodiazepine For example, for patients in group A: · 10 mg of temazepam was reduced by 2.5 mg every 2 weeks according to the following schedule: o Week 1 (10 mg) o Weeks 2 and 3 (7.5 mg) o Weeks 4 and 5 (5 mg) o Weeks 6 and 7 (2.5 mg) o Weeks 8 onwards (0 mg i.e. placebo only) · For patients in group B, the schedule was parallel with dose reduction beginning at week 13. The schedule for 5 mg nitrazepam was: o Week 1 (5 mg) o Weeks 2 to 5 (2.5 mg) o Weeks 6 to 12 (0 mg) · Schedule was adjusted for larger doses. For example, the schedule for 20 mg temazepam was: o Week 1 (20 mg) o Weeks 2 and 3 (15 mg) o Weeks 4 and 5 (10 mg) o Weeks 6 and 7 (5 mg) o Weeks 8 and 9 (2.5 mg) o Weeks 10 onwards (0 mg) Comparator: Group C (comparator group) was those who did not want to deprescribe benzodiazepines. |
| Outcomes | Successfully deprescribing
Cognitive and psychomotor tests Benzodiazepine withdrawal scale visual analog scales Health-related quality of life – sub-scales of the Medical Outcomes Study Short-form 36 questionnaire |
| Dates | Dates: Not described
Follow-up duration: One year |
| Funding sources | NHS Executive London (NHSE-LRO) Research and Development, Responsive Funding Program NHS Executive London (NHSE-LRO), Research and Development, Responsive Funding Program |
| Notes | * Group A and group C were the two groups analyzed for the purpose of this systematic review. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | Insufficient detail given as to the randomization process “Patients were randomly allocated to one of two treatment groups (A or B) in a double-blind, independent group design.” |
| Allocation concealment (selection bias) | Unclear risk | No method was described. |
| Blinding of participants and personnel (performance bias) | Low risk | All drugs were formulated in identical opaque capsules and packed with lactose placebo to appear the same throughout the trial. Dose titration regime was devised to minimize the risk of withdrawal. Participants were well blinded, including provision to avoid withdrawal effects. Tablet bottles were numbered and left with the general practitioner for patients to collect |
| Blinding of outcome assessment (detection bias) | Low risk | Researchers were blind to allocation. |
| Incomplete outcome data (attrition bias) | Low risk | Drop out rate was very low and reasons given for most. Because of the low numbers, would probably not affect the results. Drop-outs were also evenly spread across the groups. Intention-to-treat analysis was carried out. |
| Selective reporting (reporting bias) | Low risk | Method describes outcome criteria: (i) to sample the range of memory, attention and psychomotor functions sensitive to impairment by benzodiazepines; (ii) to be clinically-relevant in that most of the tests sample ‘daily-life ’ cognitive requirements; (iii) to be appropriate to and not unduly fatiguing for older adults; (iv) to monitor sleep, mood, bodily symptoms and possible withdrawal symptoms; and (v) to monitor health-related quality of life. All outcomes were reported |
| Other bias | Unclear risk | Patients wishing to discontinue were chosen hence a positive bias toward successful discontinuation. Unclear whether this constitutes a high risk of bias. No conflicts reported but funding also not reported. Difficult to see how conflicts would affect outcome in this study type. Explanation not clear of why the difference in methods for group A and B |
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