Drug Utilization Review of Benzodiazepine Use in First Nations
and Inuit Populations
Drug Use Evaluation (DUE) Bulletin - September 2005
Help on accessing alternative formats, such
as PDF, MP3 and WAV files, can be obtained in the alternate
format help section.
(326 KB)
The Non-Insured Health Benefits (NIHB) Program
provides supplementary health benefits, including prescription
and non-prescription drugs, for registered First Nations and recognized
Inuit throughout Canada. Visit our Web site at: www.healthcanada.gc.ca/nihb
Recommendations
In December 2003, the NIHB Program created
a Drug Use Evaluation Advisory Committee (DUEAC) (For further information
on the DUEAC, please see the
November 2004 NIHB Drug Bulletin.) to provide recommendations to
the Program to promote improvement in the health outcomes of First
Nations and Inuit clients through effective use of pharmaceuticals.
This DUE Bulletin reviews the Committee's
findings from its drug use evaluation of benzodiazepine claims
submitted to the NIHB Program. Based on those findings the Committee
recommends that:
- Prescribers and pharmacists be vigilant
about the risks involved with the long-term use of benzodiazepines.
- In order to promote the optimal use
of benzodiazepines in anxiety and insomnia and to avoid dependence,
new prescriptions be carefully monitored and be of limited duration
(one to four weeks for anxiety disorders and up to 14 days for
insomnia).
The DUEAC (For further information on the DUEAC, please see the
November 2004 NIHB Drug Bulletin.) of the NIHB Program recommended
that a review of benzodiazepine use be undertaken because of the
potential for overuse and abuse. This topic meets predefined criteria
as an issue the Committee would consider because enzodiazepines
are widely prescribed. In Western societies it is estimated that
10%-20% of adults regularly take benzodiazepines, despite a paucity
of evidence suggesting benefit, but clear evidence of harm (including
dependence). (Holbrook AM et al. Meta-analysis of benzodiazepine
use in the treatment of insomnia. CMAJ 2000; 162: 225-33.)
Although benzodiazepines possess other effects (for example, anticonvulsant
and muscle relaxant properties), their predominant clinical use
is in the treatment of anxiety and sleep disorders. Benzodiazepines
are also used in the acute management of symptom control associated
with serious psychiatric illnesses. When used appropriately and
for short periods of time, they are relatively safe. However with
chronic use, benzodiazepines are associated with tolerance and
addiction and in the elderly, cognitive impairment and falls. (Lader
MH. Benzodiazepines: a risk-benefit profile. CNS Drugs 1994; 1:
377-387.)
The efficacy of benzodiazepines for long term treatment of anxiety
or insomnia is controversial. Evidence of continued efficacy beyond
a few months is not well documented. Brief, interrupted courses
of treatment should be proposed at the start of therapy, perhaps
of one to four weeks' duration, with a tapered withdrawal of the
drug. As well, there is little or no rationale to using more than
one benzodiazepine at a time. (Holbrook AM et al. Meta-analysis
of benzodiazepine use in the treatment of insomnia. CMAJ 2000;
162: 225-33.), (Lader MH. Benzodiazepines: a risk-benefit profile.
CNS Drugs 1994; 1: 377-387.)
Generally the manufacturers of benzodiazepines recommend the duration
of treatment should be as short as possible with regular assessment
of the patient. The need for continued treatment should be evaluated,
especially if the patient is symptom free. In the management of
anxiety disorders, therapy with a benzodiazepine should be considered
as an adjuvant and not exceed two months, including the tapering-off
period. In the management of insomnia, therapy should be limited
to 7 to 14 days. (Compendium of Pharmaceutical and Specialties
2005), (Product Monographs)
Clinical efficacy of the various benzodiazepines is similar, but
pharmacokinetic properties can vary considerably. Duration of action
depends in part on the half-life of the drug and the presence or
absence of active metabolites. Drugs with long elimination half-lives
usually have long durations of action and are associated with prolonged
sedation. (Compendium of Pharmaceutical and Specialties 2005),
(Bazire S. Psychotropic Drug Directory 2004. Fivepin Publishing.
Salisbury 2004)
One area of concern with benzodiazepines is the use in elderly
patients. Elderly patients are especially vulnerable to the effects
of benzodiazepines; aging increases the half-life.3,7 'Beers Criteria'
lists long acting benzodiazepines (t1/2 > 100 hours) as inappropriate
for elderly patients, while short and intermediate acting agents
should only be used at reduced doses and for limited periods of
time. (Fick DM et al. Updating the Beers Criteria for potentially
inappropriate medication use in older adults. Arch Int Med 2003:
163:2716-24.)
![To Top](/web/20061213092319im_/http://hc-sc.gc.ca/images/fnih-spni/arrow_up.gif)
Purpose of this Drug Use Evaluation
The objective of this DUE was to identify patterns of benzodiazepine
prescribing and utilization among First Nations and Inuit populations
and to quantify clients at risk.
Methods
This was a retrospective analysis of an encrypted data set protecting
patient privacy. Clients of the NIHB Program who had been dispensed
a benzodiazepine from April 1, 2002 until March 31, 2004 (24 months)
comprised the study population. Benzodiazepines, covered under
the NIHB Program, were included in the study (Table).
Benzodiazepines Listed as Benefits Under NIHB
(Bazire S. Psychotropic Drug Directory
2004. Fivepin Publishing. Salisbury2004), (British Columbia Therapeutic
Initiative: Therapeutics letter November- December 2004)
Generic Name (Brand Name) |
Half-life (hrs) in
healthy adults (Half-lives vary
from patient to patient and will be influenced by age, hepatic
and renal function.) |
Diazepam Equivalents
(# of mg = 10 mg diazepam) |
Alprazolam
(Xanax®) |
12 to 15 |
1 |
Bromazepam
(Lectopam®)
|
8 to 30 |
6 |
Chlordiazepoxide
(Librium®)
|
100 |
30 |
Clobazam
(Frisium®)(Clobazam is used
mainly as an anticonvulsant) |
10 to 46 |
20 |
Clonazepam
(Rivotril®)(Clonazepam is
also used as an anticonvulsant and other conditions
such as restless legs syndrome) |
20 to 80 |
1 |
Clorazapate
(Tranxene®) |
100 |
15 |
Diazepam
(Valium®) |
100 |
10 |
Flurazepam
(Dalmane®) 100 22) |
1.5 to 5 |
0.5 |
Lorazapam
(Ativan®)
|
10 to 20 |
2 |
Nitrazepam
(Mogadon®)
|
16 to 55 |
10 |
Oxazepam
(Serax®)
|
5 to 15 |
30 |
Temazepam
(Restoril®)
|
10 to 20 |
20 |
Triazolam
(Halcion®) |
1.5 to 5 |
0.5 |
Doses of benzodiazepines vary from agent to agent and from indication
to indication. However the literature provides methods to compare
equivalent doses of benzodiazepines. Comparisons can be done using
diazepam equivalents (Bazire S. Psychotropic Drug Directory 2004.
Fivepin Publishing. Salisbury 2004) or defined daily dose (DDD).
The usual daily dose of diazepam is 10 mg or 1 DDD. The maximum
daily dose of diazepam recommended in the Compendium of Pharmaceutical
Specialties is 40 mg. (Compendium of Pharmaceutical and Specialties
2005).
![To Top](/web/20061213092319im_/http://hc-sc.gc.ca/images/fnih-spni/arrow_up.gif)
The system of Defined Daily Doses (DDDs) developed and maintained by the World Health Organization (WHO) standardizes the measurement of drug prescribing. Drugs are given a value representing the average maintenance dose per day in its main indication in adults. It must be emphasized the DDD is simply a unit of measure. For more information on the DDD system, please refer to the World Health Organization Web site.
The primary outcome measure was to determine the overall utilization
of benzodiazepines among NIHB clients; secondary outcomes included
identifying clients at risk for benzodiazepine abuse and patterns
of benzodiazepine use among the elderly. The benchmark for abuse
was set at the equivalent of 40 mg of diazepam per day, along with
parameters around numbers of prescribers, providers and early refills.
(Holbrook AM et al. Meta-analysis of benzodiazepine use in the
treatment of insomnia. CMAJ 2000; 162: 225-33.), (Compendium of
Pharmaceutical and Specialties 2005).
Key Findings
- For the period of analysis (April 2002 to March 2004) 80,495
individuals had at least one claim for a benzodiazepine in the
NIHB Program. There were over 900,000 individual claims for benzodiazepines.
Claimants were predominantly female (63%), between the ages of
18 and 64 years (87%) and residing in western regions (Figure
I).
Figure I. Percent of Total NIHB
Eligible Population with at Least 1 Benzodiazepine Claim (by Region)
![Percent of total NIHB eligible population with at least 1 Benzodiazepine claim (by Region).](/web/20061213092319im_/http://hc-sc.gc.ca/fnih-spni/images/fnihb-dgspni/pubs/drug-med/due_region_e.jpg)
- Figure II describes the percentage of clients with
at least one prescription exceeding the equivalent of 40 mg diazepam
per day. This data is representative of all age groups, and is
not adjusted for age.
Figure II. Percent of Clients with at least
one Rx >40 mg Diazepam Equivalents
- Demographics of benzodiazepine use within the NIHB
populations match the demographics of populations from both published
and unpublished data. About 10 % of NIHB clients had a prescription
for a benzodiazepine in the past year. Overall, more females
than males use benzodiazepines. (Holbrook AM et al. Meta-analysis
of benzodiazepine use in the treatment of insomnia. CMAJ 2000;
162: 225-33.), (British Columbia Therapeutic Initiative: Therapeutics
letter November- December 2004)
- The use of benzodiazepines in elderly clients is of concern,
as there appears to be a higher prevalence of prescribing in
the First Nations & Inuit seniors population. Over the two
year period, 30.5% of clients > 64 years of age received a
benzodiazepine prescription for a dose greater than 1 DDD. This
is contrast to a published study from Quebec that showed 17.8%
of seniors were prescribed this dose over a oneyear period. As
well, 24.9% of elderly NIHB clients received two or more benzodiazepines
concurrently during the study period. (Egan MY et al. High daily
doses of benzodiazepines among Quebec seniors: prevalence and
correlates. BMC Geriatrics 2001.1:4)
- Figure III illustrates the distribution of all clients at highest
risk of benzodiazepine overuse and misuse (defined as benzodiazepine
prescriptions filled by more than 8 providers (pharmacies), benzodiazepine
prescriptions from more than 11 prescribers, and have early refills
[refilled less than 2/3 of days supply] on at least 4 occasions).
Figure III. Distribution of
NIHB clients at highest risk of benzodiazepine overuse and misuse,
showing overlap of indicators of risk.
![Distribution of NIHB clients at highest risk of benzodiazepine overuse and misuse, showing overlap of indicators of risk.](/web/20061213092319im_/http://hc-sc.gc.ca/fnih-spni/images/fnihb-dgspni/pubs/drug-med/due_region3_e.jpg)
See revised
graphic information
![To Top](/web/20061213092319im_/http://hc-sc.gc.ca/images/fnih-spni/arrow_up.gif)
Limitations of the Analysis
The use of administrative claims data for DUE analysis is not
without its shortcomings and as a result, there are three significant
limitations to this evaluation.
- For each claim, the recorded quantity and days' supply is
not always accurate. This is due to the manner by which the data
is entered by the provider. Claims often contain keypunch errors
and calculation estimates. For example, the provider may enter
the total number of milligrams dispensed instead of the number
of tablets dispensed in the claim.
The method most often employed to detect the effect of these
data shortcomings on the analysis was to run the programs with
all data included and then to run the program a second time with
the questionable claims removed. It was determined that the questionable
claims had no significant effects on the results.
- The analysis only includes claims that were paid by NIHB and
does not include claims that were paid by other insurers or by
cash. This is a limitation for this study since clients who are
at risk of benzodiazepine abuse might choose to pay cash for
some prescriptions.
- The denominator used when reporting utilization rates as a
percent of population (Figure I) was the total number of NIHB
eligible persons. It includes persons that are covered under
contribution agreements and therefore not captured in NIHB claims
data. This has the effect of under-reporting the actual percent
values. Therefore, the true population rates can be expected
to be marginally higher than the reported rates.
![To Top](/web/20061213092319im_/http://hc-sc.gc.ca/images/fnih-spni/arrow_up.gif)
Benzodiazepine Withdrawal Strategies
While the management of benzodiazepine withdrawal is beyond
the scope of this report, listed below is information on withdrawal
strategies. It is important that health care providers inform
patients (and their families) of what to expect during withdrawal.
Pharmacists can help physicians and patients keep track of tapering
schedules.
- Ashton H. Benzodiazepines: how they work and how to withdraw.
Aug. 2002. http://www.benzo.org.uk/manu al/bzsched.htm.
- Baillargeon L, Landreville P, Verreault R. et al. Discontinuation
of benzodiazepines among older insomniac adults treated with
cognitive-behavioural therapy combined with gradual tapering:
a randomized trial. CMAJ 2003;169 (10):1015-20.
- The Addictions Medical Advisory Committee, Government of
Saskatchewan.
Withdrawal
management, protocols, guidelines and services (PDF version),
April 2001, pg. 11-13.
Conclusions
Among First Nations and Inuit, the rate of overuse and potential
misuse appears to be the same as the rest of the general population
in Canada. A recent bulletin from British Columbia's Therapeutic
Initiative describing the use of benzodiazepines within that province
confirms overall benzodiazepine use among First Nations and Inuit
is similar in usage patterns, demographics (females > males,
age) and percentage of users (10%) to other populations.
A very small percentage of First Nations and Inuit clients appear
to be at high risk (< 1%) because of benzodiazepine overuse
and misuse. "High risk" indicates these clients have
prescriptions from several physicians, go to several pharmacies
to fill their prescriptions for benzo-diazepines and are early
for refills.
There are concerns however, about regional trends, high volume
prescribers, use of long-acting benzodiazepines, and continued
use in the elderly.
Efforts are underway to review the benzodiazepines listed under
the NIHB drug benefit list, with the aim to remove (or restrict
access to) certain long-acting benzodiazepines. Prescriber, provider
and community profiles are being developed to help monitor benzodiazepine
use, with an effort to promote optimal prescribing of these drugs.
![To Top](/web/20061213092319im_/http://hc-sc.gc.ca/images/fnih-spni/arrow_up.gif)
Summary of Initiatives Addressing Benzodiazepine Use Among
First Nations and Inuit
- Attempt to address concerns
with regional trends and prescribing in the elderly with
further DUE activities and consultations with pharmacists
and physicians.
- Attempt to identify new benzodiazepine
users and address continued use with prescribers and providers.
- Development of prescriber,
provider and community profiles.
- Removal of certain long-acting
benzodiazepines on the benefit list.
Members of the NIHB DUEAC
Richard MacLachlan (Chair)
Head, Department of Family Medicine
Dalhousie University
Bob Nakagawa (co-Chair)
Director, Pharmacy Services
Fraser Health Authority
Ingrid Sketris
Professor, College of Pharmacy
Dalhousie University
Dawn Frail
Manager, Drug Technology Assessment
Drug Evaluation Alliance of Nova Scotia
Nova Scotia Department of Health
Michael Perley
Assistant Professor of Family Medicine
Dalhousie University
Cornelia Wieman
Consultant/Psychiatrist, Six Nations Mental Health
Services Co-Director, Indigenous Health Research Development
Program University of Toronto
Marlyn Cook
Mohawk Council of Akwasasne
Department of Health
Derek Jorgenson
Coordinator, Clinical Pharmacy Services
Saskatoon Health Region
|