Comparison of Dental Benzodiazepine Prescriptions From the U.S., England, and Australia from 2013 to 2018

Abstract

Objectives:

Benzodiazepines contribute to substance use disorder, and are often part of polydrug abuse, most frequently with opioids. While dental opioid prescribing differs significantly between countries, little is known about the patterns of dental benzodiazepine prescribing. The aim of this study was to compare dental prescribing of benzodiazepines between the United States (US), England and Australia between 2013–2018.

Methods:

Population-level data were accessed from national datasets for each country for dental benzodiazepine prescriptions. Outcomes measures of dental benzodiazepine prescribing included (1) prescribing rates by population for each year and (2) the quantity and relative proportion of benzodiazepines by type for each country. The analysis was conducted in 2020.

Results:

Between 2013–2018, US dentists prescribed 23 times more than English dentists, and seven times more than Australian dentists by population. During the study period, the rate of dental benzodiazepine prescribing decreased in England and the US, but increased in Australia, so in 2018, US dentists prescribed 28 times more than English dentists, and 6 times more than Australian dentists (US: 3.10prescriptions/1000population; England: 0.11prescriptions/1000population; Australia: 0.50prescriptions/1000population). US dentists prescribed a wider variety of benzodiazepines compared to English and Australian dentists. Diazepam was most commonly prescribed in all countries. In the US, triazolam, lorazepam and alprazolam were next most commonly prescribed. Temazepam was next most frequent in England and Australia.

Conclusions:

Significant variation in benzodiazepine prescribing rates and types were seen between the countries. To improve patient safety, further investigation into the appropriate use and choices of benzodiazepines in dental practice is needed.

Introduction

Substance abuse disorder is a significant public health issue. Benzodiazepines are commonly misused in the United States (US) and Australia,^{1, 2} and often in combination with other drugs, especially opioids.^3–5 A retrospective study of the National Poison Data System in the US showed that the abuse or misuse of benzodiazepines in combination with opioids increased significantly from 2000 to 2014.¹ In 2013, benzodiazepines were associated with 31% of fatal overdoses of prescription drugs.⁶ Additionally, the rate of pediatric benzodiazepine exposures increased by 54% from 2000 to 2015, with alprazolam, clonazepam and lorazepam most commonly implicated.⁵

Benzodiazepines work by various methods in polydrug abuse: they can augment the euphoria associated with opioid use, mitigate withdrawal states and enhance the effects of alcohol.³ The US Food and Drug Administration (FDA) has applied its most prominent warning (the boxed warning) describing the risks of dependence and misuse for all benzodiazepines.⁷

More than one-in-ten adults suffers extreme anxiety associated with dental visits⁸ and dentists may prescribe benzodiazepines as premedication to manage dental phobia.^{9, 10} Of concern, the dispensed use of benzodiazepines increased by 16% from 2013–2016 in Australia.¹¹ Dental prescribing of benzodiazepines may contribute significantly to substance abuse, misuse or diversion, and further insights are needed to inform targeted interventions to optimise prescribing. Recent focus has been on dental opioid prescribing, but much less attention to the prescribing of benzodiazepines in dentistry. This study aimed to compare dental prescribing of benzodiazepines in the US, England and Australia between 2013–2018.

Methods

This population-level analysis of all dental benzodiazepine prescriptions dispensed from outpatient or community pharmacies between 2013–2018 in US, England and Australia followed the Strengthening the Reporting of Observational Studies in Epidemiology guideline.¹² Outpatient prescription information for dentists from nationally representative sources were obtained, which included dispensed prescriptions for both oral and parenteral benzodiazepines. Prescribing rates were calculated using mid-year populations for each year 2013–2018.

Data sources

Prescribing data for the US were accessed from IQVIA LRx. These data represented 92% of all dispensed outpatient prescriptions in the US and include commercially insured, Medicare, Medicaid and cash pay patients. The US population size was obtained from the US Census Bureau.¹³

Prescribing data for England were accessed from the National Health Service (NHS) Digital Prescription Cost Analysis.¹⁴ These data represented over 98% of all dispensed outpatient benzodiazepine prescriptions in the UK¹⁵ for patients treated under the NHS scheme. England’s population size was obtained from the UK Office for National Statistics.¹⁶

Prescribing data for Australia were obtained from the Department of Health.¹⁷ All benzodiazepines subsidised by the Australian Government for dental prescribers listed on the Pharmaceutical Benefits Scheme (PBS) and Repatriation Pharmaceutical Benefits Scheme (RPBS) were included.¹⁸ Approximately 93% of PBS/RPBS prescriptions are from community settings, which would be the predominant source of dental prescriptions.¹⁹ The population size was obtained from the Australian Bureau of Statistics.²⁰

The University of Illinois at Chicago Investigational Review Board deemed that this study was exempt from review and informed consent. English data are available via request to the NHS Business Services Authority under the UK Freedom of Information Act 2000 and their use is licensed under the terms of the Open Government Licence for Public Sector Information.²¹ The data from Australia is aggregated and publicly available so ethics approval is not required.¹⁷

Outcomes

Two outcomes of dental benzodiazepine prescribing were measured: (1) prescribing rates (number of benzodiazepine prescriptions dispensed per 1000 population) and (2) an overall number and relative proportions of benzodiazepines by type for each country. The analyses were conducted in 2020.

Statistical Analysis

Poisson regression was used to derive p-values assessing differences in prescribing rates by country, with a 2-sided P<0.05 considered statistically significant. Poisson exact confidence intervals for population-based prescribing rates were applied. All statistical analyses were conducted using Stata 14.0 (College Station, TX).

Results

From 2013–2018, dentists in the US prescribed benzodiazepines 23 times more frequently (mean 3.20 prescriptions/1000 population) compared to English dentists, (mean 0.14 prescriptions/1000 population) and 7 times more than Australian dentists (mean 0.45 prescriptions/1000 population), when adjusting for population.

From 2013–2018, the dental prescribing of benzodiazepines decreased from 3.17 prescriptions/1000 population to 3.10 prescriptions/1000 population in the US and from 0.17 prescriptions/1000 population to 0.11 prescriptions/1000 population in England. However, Australian dental prescriptions increased from 0.40 prescriptions/1000 population to 0.50 prescriptions/1000 population. In 2018, dentists in the US prescribed benzodiazepines 28 times more frequently (3.10 prescriptions/1000 population) compared to English dentists (0.11 prescriptions/1000 population) and 6 times more than Australian dentists (0.50 prescriptions/1000population), adjusting for population (Table 1). The differences in the prescribing rates of all countries for each year was statistically significant (p<0.0001). Changes in prescribing rates per year are shown in Figure 1.

Table 1.

Prescribing outcomes and proportion of benzodiazepine agents

	2013		2014		2015		2016		2017		2018
Population-based prescribing rate (# prescriptions/1000 population) a
United States	3.17 (3.16–3.17)		3.20 (3.20–3.21)		3.25 (3.25–3.26)		3.24 (3.23–3.24)		3.21 (3.20–3.21)		3.10 (3.09–3.10)
US mid-year population	315,993,715		318,301,008		320,635,163		322,941,311		324,985,539		326,687,501
England	0.17 (0.17–0.17)		0.16 (0.16–0.17)		0.15 (0.14–0.15)		0.13 (0.13–0.13)		0.12 (0.12–0.12)		0.11 (0.11–0.12)
England mid-year population	53,865,800		54,316,600		54,786,300		55,268,100		55,619,400		55,977,000
Australia	0.40 (0.39–0.40)		0.43 (0.42–0.44)		0.42 (0.42–0.43)		0.44 (0.43–0.45)		0.48 (0.47–0.48)		0.50 (0.49–0.50)
Australian mid-year population	23130900		23490700		23781200		24127200		24598900		24992400
Proportion of benzodiazepine agents dispensed by type agent and year
United States
Alprazolam	98,692	9.9	99,798	9.8	99,494	9.5	95,026	9.1	92,441	8.9	79,709	7.9
Chlordiazepoxide	1,183	0.1	919	0.1	812	0.1	557	0.1	501	0.0	412	0.0
Clonazepam	23,448	2.3	22,935	2.2	21,693	2.1	18,094	1.7	17,683	1.7	14,364	1.4
Clorazepate	938	0.1	765	0.1	721	0.1	674	0.1	597	0.1	532	0.1
Diazepam	457,731	45.7	454,668	44.6	458,951	44.0	451,816	43.2	439,778	42.2	416,861	41.2
Estazolam	135	0.0	143	0.0	116	0.0	168	0.0	104	0.0	60	0.0
Flurazepam	518	0.1	548	0.1	324	0.0	295	0.0	143	0.0	98	0.0
Lorazepam	124,143	12.4	125,877	12.3	127,504	12.2	124,598	11.9	122,165	11.7	116,438	11.5
Midazolam	7,639	0.8	8,543	0.8	8,811	0.8	9,114	0.9	9,049	0.9	10,050	1.0
Oxazepam	732	0.1	725	0.1	681	0.1	636	0.1	545	0.1	498	0.0
Temazepam	3,757	0.4	3,673	0.4	3,142	0.3	2,450	0.2	2,211	0.2	1,844	0.2
Triazolam	282,240	28.2	301,151	29.5	320,545	30.7	341,860	32.7	357,564	34.3	371,297	36.7
Total	1,001,156	100.0	1,019,745	100.0	1,042,794	100.0	1,045,288	100.0	1,042,781	100.0	1,012,163	100.0
England
Diazepam	6,574	72.0	6,356	71.8	5,859	73.2	5,382	74.8	5,076	76.9	4,936	77.8
Temazepam	2,558	28.0	2,501	28.2	2,141	26.8	1,812	25.2	1,523	23.1	1,409	22.2
Total	9,132	100.0	8,857	100.0	8,000	100.0	7,194	100.0	6,599	100.0	6,345	100.0
Australia	N	%	N	%	N	%	N	%	N	%	N	%
Diazepam	7,084	77.4	7,894	78.4	7,991	79.3	8,651	81.3	9,428	80.6	10,051	81.1
Nitrazepam	120	1.3	101	1.0	90	0.9	71	0.7	77	0.7	80	0.6
Oxazepam	294	3.2	382	3.8	381	3.8	283	2.7	308	2.6	351	2.8
Temazepam	1,658	18.1	1,697	16.8	1,616	16.0	1,635	15.4	1,880	16.1	1,912	15.4
Total	9,156	100.0	10,074	100.0	10,078	100.0	10,640	100.0	11,693	100.0	12,394	100.0

^aAll p-values for test of equality of yearly population-based prescribing rates are p<.0001

Figure 1.

Prescribing rate of benzodiazepines by population from 2013–2018

Most common benzodiazepine prescriptions per country

Diazepam prescriptions accounted for the most benzodiazepines in the US, but their proportion reduced steadily from 2013–2018, with 457,731 prescriptions written in 2013 and 416,861 prescriptions written in 2018, which represents a reduction of 9% of dispensed diazepam prescriptions. Triazolam was the second most commonly dispensed benzodiazepine in the US, increasing from 282,240 dispensed prescriptions in 2013 to 371,297 in 2018, representing an increase of 32%.

In England, diazepam prescriptions were most commonly dispensed. Diazepam decreased by 25% from 2013–2018, accounting for 6,574 prescriptions dispensed in 2013 and 4,936 dispensed in 2018. Temazepam, the second most frequent benzodiazepine in England, decreased by 45% from 2013–2018, accounting for 2,558 dispensed prescriptions in 2013 and 1,409 dispensed prescriptions in 2018.

Similar to the US and England, diazepam was the most commonly dispensed benzodiazepine in Australia. Diazepam increased by 42% from 2013–2018, accounting for 7,084 dispensed prescriptions in 2013 and 10,051 prescriptions in 2018. Similar to England, temazepam was the second most popular benzodiazepine in Australia, accounting for 1,658 prescriptions in 2013 and 1,912 prescriptions in 2018, representing an increase of 15%.

A wider variety of benzodiazepines were prescribed by US dentists compared to English and Australian dentists (Table 1).

Discussion

Substantial variation exists in the rate of benzodiazepine prescribing by dentists internationally. This study demonstrated US rates were highest and English rates were lowest. This is the first such international comparison and suggests significant potential for optimising dental benzodiazepine prescribing.

The variation in benzodiazepine prescribing was striking in comparison to overall oral health (including missing teeth, edentulousness and degree of caries experience) which are similar between the countries.^22–24 Furthermore, the wide range of benzodiazepine types prescribed by dentists in the US in this study was notable, when compared to a much narrower set of drugs prescribed by dentists in England. Additionally, dental opioid prescribing rates and choices have found to exhibit similar differences between these countries^{25, 26} and has received more focus in the literature. Thus, further research is needed to determine the provision and need for such a wide variety of benzodiazepines in dentistry.

The need for the wide variety of benzodiazepine types prescribed by dentists in the US, compared to the other countries, is questionable. All benzodiazepines can produce withdrawal symptoms such as rebound anxiety on abrupt discontinuation, which is more so for the short-acting BZDs such as alprazolam and triazolam.^{27, 28} Characteristics of benzodiazepines that are associated with reinforcing effects include those that have a rapid time to peak plasma concentration and high potency, such as lorazepam and alprazolam, as well as those that are highly lipophilic so are able to cross the blood brain barrier quickly.³ Awareness of the abuse potential of these drugs should be highlighted in continuing education in dentistry.

In dentistry, benzodiazepines are most often given orally for premedication for dental procedures to allay anxiety.^{9, 10} However, benzodiazepines can also be given for conscious sedation purposes and administered either orally or intravenously to produce a deeper degree of sedation.^{29, 30} In the US, the use of intravenous sedation can be performed in outpatient clinics with appropriate training.³¹ In England, dentists need to be accredited with additional training to perform intravenous sedation. Benzodiazepines used in this way are not prescribed using an outpatient prescription and are therefore not included in these data, however the number of sedation services relative to the English population is small.³² In Australia, dentists also need further training and endorsement to provide conscious sedation,³³ and the use of intravenous midazolam would also not be captured in these data. However, only 106 practitioners were endorsed for conscious sedation in Australia in June 2020, representing 0.6% of all registered dentists and dental specialists.³⁴ These differences in the types of sedation may partly explain the disparity in prescribing rates in these data.

Dental conditions can be managed by different providers in the different countries. In the US, benzodiazepines can be used by general dentists to treat chronic conditions such as temporomandibular joint dysfunction and burning mouth syndrome.^{35, 36} In both the UK and Australia, these conditions are mostly managed by oral medicine specialists. Indeed, the American Academy of Oral Medicine recommends clonazepam for burning mouth syndrome.³⁷ Benzodiazepines will likely be used for longer periods for these conditions compared to premedication for a single dental procedure.

Guidelines for each country differ for use of these medicines in dentistry, as well as the regulation of these drugs at national levels, which may partly explain the differences in prescribing rates. The low rate of benzodiazepine use in England is likely related to the 2006 report: ‘The Regulation of Controlled Drugs in the Community’ and subsequent changes in the legal framework for their use.³⁸ There are also well documented guidelines on prescribing of benzodiazepines for sedation and conscious sedation in the UK,^{39, 40} as well as the restricted list of drugs that dentists are able to prescribe on the NHS.⁴⁰ The provision of controlled drugs such as benzodiazepines in the UK by private dentists requires them to use specific tracked NHS prescription pads, so the prescribing of these drugs are monitored. In Australia, several benzodiazepines (i.e. chlordiazepoxide, clorazepate, estazolam, triazolam) are not available.⁴¹

These possible reasons for variation between the countries may partly explain the disparity between the prescribing rates, but also provide possible ways to reduce the prescribing of benzodiazepines in the US. Limitation of the range of benzodiazepines at a national level and recommendations through guidelines are possible ways to appropriately restrict and reduce the use of benzodiazepines by dentists in the US. In addition, the inclusion of the misuse of benzodiazepines in further education of dentists in both Australia and the US to bring awareness of this potential overlooked problem is also recommended.

Limitations

There are several limitations to these data. First, the authors recognise there are differences in the datasets available internationally and selected the best available for this comparison study. Although relatively few in number, private prescribing by dentists in Australia and England was excluded unlike for the US data. The Australian and English data are limited to patients who were prescribed benzodiazepines under the PBS/RPBS and NHS systems, respectively. Australia and England datasets are publicly available whereas the US data is proprietary. Second, a survey of prescribing preferences showed that Australian dentists do prescribe other benzodiazepines, including lorazepam, although it was proportionally small.⁴² Medications administered during dental surgeries in hospitals or ambulatory surgery centres are not included in this data and English data was limited to oral formulations. However, parenteral benzodiazepines only accounted for 0.27% of benzodiazepines in the US (16,744 prescriptions) and 0.02% in Australia (14 prescriptions). Third, the data were aggregated and de-identified, so it was not possible to determine prescription details about the regimen prescribed, the patients/conditions for which they were prescribed, or the appropriateness of each prescription. Finally, access to oral health services is similar in Australia and England but slightly higher in the US. Provision of dental care in each country is different: the US is dominated by private clinics, whereas in England and Australia there is a mix of public and private provision. For these reasons, it has been possible to describe but not determine reasons for the variation in dental benzodiazepine prescribing identified between the counties.

Future research can focus on characteristics of specific age groups and population cohorts that are being prescribed benzodiazepines, such as some special needs patients who may benefit more from the use of oral benzodiazepines rather than the use of general anaesthetic. Investigating alternative ways of managing anxious patients for clinicians who choose to not prescribe benzodiazepines may present other options for dentists. Finally, investigating regional differences within the countries for benzodiazepines prescriptions and correlating this with substance abuse disorders, as well as the prevalence of benzodiazepine abuse between the countries could be another possible area of further research.

Conclusions

Given the substantial variation in prescribing rates demonstrated, these data strongly suggest there is significant opportunity to improve patient safety by optimising the amount and types of benzodiazepines prescribed by dentists. Whilst benzodiazepines have received less international attention in dentistry than opioid prescribing, benzodiazepines may be equally important in relation to tackling substance misuse disorder.