New users of benzodiazepines: implications for elder patient safety

1. New users of benzodiazepines: implications for elder patient safety G. Bartlett, PhD Family Medicine McGill University

2. Outline • Benzodiazepine use in the elderly • Objectives of study • Methods • Population & data sources • Results – new users vs non-users • Results – predictors of new use • Conclusions, Limitations • Future Directions

3. Benzodiazepines - review • Sedative/hypnotics: • hypnotic, anxiolytic, anticonvulsant, muscular relaxant, amnesic • high efficacy, rapid onset of action, low toxicity • unique among psychotropics for multiple indications and relative safety compared with other sedative/hypnotics

4. Concerns about Benzodiazepines • psychomotor impairment • paradoxical excitement • tolerance, dependence and withdrawal effects with long term use • injuries from falls

5. Concerns about Benzodiazepinesfor the Elderly Due to changes that occur with normal aging, elderly demonstrate increased sensitivity to: • psychomotor impairment • memory impairment • rebound or withdrawal effects • interactions with other medications/conditions

6. Use of Benzodiazepines:Why the Elderly? • insomnia can be a “pathological” feature associated with age • anxiety due to other illnesses • more likely to suffer acute grief reactions • fewer complications with benzodiazepines than with tricyclic anti-depressants and anti-psychotics

7. Why are we still discussing benzodiazepine safety? • Risk from injuries from falls for benzodiazepines still in dispute • Physicians may be prescribing benzodiazepines perceived to be safer to higher risk patients • Pre-existing risk factors may be cause confounding in published studies What risk factors for falls are present before a benzodiazepine is prescribed?

8. Methods • All patients >65 years with no benzodiazepine script in baseline year • Risk factors for falls assessed in baseline year: • age & sex • clinical characteristics • disabilities & impairments • prior hospitalizations • prior health care use • use of other prescription medication. • 5 years of follow-up until first benzodiazepine script dispensed – product name identified

9. Benzodiazepines available in QC • Triazolam (Halcion) • Midazolam (Versed) – IV only • Alprazolam (Xanax) • Bromazepam (Lectopam) • Lorazepam (Ativan) • Oxazepam (Serax) • Nitrazepam (Mogadon) • Temazepam (Restoril) • Clobazam (Frisium) • Clonazepam (Rivotril) • Diazepam (Valium) • Flurazepam (Dalmane) • Chlordiazepoxide (Librium) • Clorazepate* (Traxene)

10. Data Sources: The Quebec Health Care Databases • Beneficiary Database: all Quebec residents, age, sex, date of death, address • Pharmaceutical Database: all claims for prescriptions dispensed to elderly and welfare recipients in Quebec • Medical Services Claims: all medical services provided on a fee-for-service basis (90%) to Quebec residents • Hospitalization Database: all discharges from Quebec hospitals - dates for hospitalization

11. Study Sample

12. Study Overview Baseline Follow-up Jan. 1989 Jan. 1990 Dec. 1994

13. Results - general • average age 73.4 years with 52% women • 78,367 (31%) new benzodiazepine users • New users had an almost two-fold increase in use of anti-depressants and sedatives, cardiac medications, anti-hypertensive agents, vasodilators and diuretics • 9.5% of new users versus 5.6% of non-users filled at least one prescription for another psychotropic medication • 44% of new users vs 38% of non-users filled at least one prescription for medications that affect motor stability • New users were more likely to have depression and arthritis, and used more health care services than non-users

17. Results – product specific • decreased risk of starting oxazepam and flurazepam for older ages • women were more to be new users of the majority of the benzodiazepines except temazepam and flurazepam • each additional prescribing physician seen increased by risk of new use by 5-15% • having an fall injury decreased risk for lorazepam (HR=0.93, p=0.01) and diazepam (HR=0.86, p=0.04) and an increased probability for chlordiazepoxide (HR=1.34, p=0.04)

18. Results – disabilities and impairments • depression was strongly associated with new use except triazolam and temazepam -particularly strong for alprazolam (HR=1.98, p<0.0001) and clonazepam (HR=2.46, p<0.0001) • weaker but consistently positive increased risk for arthritis • neurological disorders (including dementia and Parkinson’s disease) and clonazepam (HR=2.24, p<0.0001); • alcohol abuse and both oxazepam (HR=1.55 p=0.001) and chlordiazepoxide (HR=12.1, p<0.0001) • drug abuse with bromazepam (HR=2.34, p=0.0008).

19. Results – disabilities and impairments • strongest and most consistent associations were seen for use of anti-depressants as well as other psychotropic medications (anti-psychotics and non-benzodiazepine sedatives, lithium or l-tryptophan) • filling a prescription for an anti-depressant significantly increased risk varying from a 23% increase for diazepam (HR=1.23) to more than tripling the hazard for clonazepam (HR=3.13) • use of anti-psychotics, other sedatives, and lithium or l-tryptophan increased risk by more than double for new clonazepam and flurazepam use and over five times for clonazepam (HR=5.19, p<0.0001).

20. Conclusions • Factors associated with new benzodiazepine use vary considerably among the individual products • Physicians appear to be “channeling” new users based on own criteria – not necessarily evidence based • Any research on risk needs to account for these factors by individual products

21. Limitations • under-diagnosis and under-reporting of the treatment of certain diseases • anxiety and insomnia were often not coded in the database making it difficult to assess the association between these diagnoses and benzodiazepine use • proxy measure of use (dispensed prescription) • no prescription information available during hospitalization

22. Future Directions • Why benzodiazepines are chosen by physicians – are other risk factors accounted for? • Role of risk in guidelines recommendations… • Methods to reduce risk of falls – smart alerts? • Investigations of risk from falls – are other risk factors accounted for? • Is dose adjusted for in high risk patients?

23. Questions & Comments gillian.bartlett@mcgill.ca