Prescription opioid misuse in the United States and the United Kingdom: Cautionary lessons

International Journal of Drug Policy 25 (2014) 1124–1130

Contents lists available at ScienceDirect

International Journal of Drug Policy journal homepage: www.elsevier.com/locate/drugpo

Policy analysis

Prescription opioid misuse in the United States and the United Kingdom: Cautionary lessons Daniel F. Weisberg a,1 , William C. Becker b,a , David A. Fiellin a , Cathy Stannard c,∗ a b c

Yale University School of Medicine, Department of Internal Medicine, New Haven, CT, United States VA Connecticut Healthcare System, West Haven, CT, United States Macmillan Centre Frenchay Hospital, Bristol, UK

a r t i c l e

i n f o

Article history: Received 8 December 2013 Received in revised form 3 June 2014 Accepted 22 July 2014 Keywords: Opioid analgesics Health policy Public health Prescription drug overdose

a b s t r a c t In the United States, opioid analgesics have increasingly been prescribed in the treatment of chronic pain, and this trend has accompanied increasing rates of misuse and overdose. Lawmakers have responded with myriad policies to curb the growing epidemic of opioid misuse, and a global alarm has been sounded among countries wishing to avoid this path. In the United Kingdom, a similar trend of increasing opioid consumption, albeit at lower levels, has been observed without an increase in reported misuse or drug-related deaths. The comparison between these two countries in opioid prescribing and opioid overdose mortality underscores important features of prescribing, culture, and health systems that may be permissive or protective in the development of a public health crisis. As access to opioid medications increases around the world, it becomes vitally important to understand the forces impacting opioid use and misuse. Trends in benzodiazepine and methadone use in the UK as well as structural elements of the National Health Service may serve to buffer opioid-related harms in the face of increasing prescriptions. In addition, the availability and price of heroin, as well as the ease of access to opioid agonist treatment in the UK may limit the growth of the illicit market for prescription opioids. The comparison between the US and the UK in opioid consumption and overdose rates should serve as a call to action for UK physicians and policymakers. Basic, proactive steps in the form of surveillance – of overdoses, marketing practices, prescribers, and patients – and education programs may help avert a public health crisis as opioid prescriptions increase. © 2014 Elsevier B.V. All rights reserved.

Background In the United States, opioid treatment of chronic pain is the focus of urgent attention due to increasing trends in misuse and non-fatal and fatal overdose among those to whom the opioids are prescribed as well as those who obtain them illicitly. Opioid overdose is now the second leading cause of accidental death in the United States after motor vehicle accidents (Centers For Disease Control and Prevention, 2010). These trends parallel an increase in opioid prescriptions (Hall et al., 2008). Policymakers have responded with efforts to curb the growing epidemic of opioid misuse, and a global

∗ Corresponding author at: Pain Clinic, Sherston Building, Southmead Hospital, Bristol, BS10 5NB, UK. E-mail addresses: [email protected] (D.F. Weisberg), [email protected] (C. Stannard). 1 4th: Brigham and Women’s Hospital, Department of Internal Medicine, Boston, MA, United States. http://dx.doi.org/10.1016/j.drugpo.2014.07.009 0955-3959/© 2014 Elsevier B.V. All rights reserved.

alarm has been sounded among countries wishing to avoid this epidemic. In the UK, a similar trend of increasing opioid prescriptions, albeit at lower levels, has been observed without an increase in reported misuse or drug-related deaths. Is there a protective feature of the UK healthcare system, or is an epidemic lurking at a moment when opioid consumption is at a similar level to the US’ when its problems began to unfold more than a decade ago? In this narrative review we compare two highly developed societies and health care systems – those of the US and the UK – in opioid prescribing, misuse and opioid overdose mortality; then, we underscore important features of prescribing, culture and health systems that may be permissive or protective in the development of a public health crisis. Based on the consensus of the authors, we reference events that represent important milestones in opioid prescribing practices or regulatory processes. Finally, we consider the policies aimed at safety in opioid prescribing in these two countries. As access to opioid medications, hailed as a human right (Lohman, Schleifer, & Amon, 2010), increases around the world, it becomes

D.F. Weisberg et al. / International Journal of Drug Policy 25 (2014) 1124–1130

Morphine Equivalents Per Capita Per Year

900

Opioid Consumption Per Capita US and UK 1990-2010

800 700 600 500 400

US

300

UK

200 100 0

Year

Fig. 1. Opioid consumption in the US and UK (DCAMC, 2012). Data compiled by the Drug Control and Access to Medicines Consortium reflects opioids (fentanyl, hydromorphone, methadone, morphine, oxycodone, pethidine) distributed at the retail level reported by the International Narcotics Review Board. Data does not reflect specific clinical indications for opioid use (e.g., methadone treatment for pain or for opioid agonist treatment of addiction).

imperative to understand the forces impacting opioid use and misuse. Trends in opioid prescribing Opioid prescribing for chronic non-cancer pain is increasing in the US and UK. This has occurred in spite of a paucity of evidence regarding the efficacy of opioid therapy for chronic non-cancer pain and a growing literature surrounding its harms (Kalso, Simpson, Slappendel, Dejonckheere, & Richarz, 2007; Noble et al., 2010; Okie, 2010). Although the US currently consumes more opioids per capita than the UK, both countries have seen increases in opioid consumption over the last two decades (DCAMC, 2012). Notably, the per capita consumption of opioids in the UK in 2010 was comparable to that of the US in 1999, which was the beginning of a steep increase in opioid prescribing, arguably a “tipping point” in opioid misuse in the US (see Fig. 1). The types of commonly prescribed opioids differ between the US and the UK. In the US, the most prescribed schedule II opioid is oxycodone with acetaminophen, and the most prescribed schedule III opioid is hydrocodone with acetaminophen, also the most commonly prescribed medication in the US (TOP 200 Products of 2011, 2012). In the UK, the most prescribed class A (schedule II) opioid is morphine, and the most prescribed class B (schedule III) opioid is codeine with acetaminophen, which is now the eleventh most commonly prescribed medication in the England (Addiction to Medicine, 2011). Of note, Tramadol, which has weak agonist properties on the opioid receptor, has recently been classified as a scheduled substance in the UK and US. Opioid misuse in the US and UK Comparing opioid misuse requires a standard nomenclature. Since the nomenclature is not always consistent in the literature, for the purposes of this review, the term misuse will be used as a general term for behavioral problems – ranging from use other than as prescribed to addiction – that are associated with opioid use (Table 1). According to national surveys, prescription opioid misuse is second only to cannabis in illicit drug use in the US with approximately 2% of the adult population reporting nonmedical use of prescription analgesics (NSDUH, 2009). Despite the lack of similar

1125

surveys in the UK, it is clear that the prevalence of prescription opioid misuse represents a smaller proportion of illicit drug use, and patients presenting for treatment of prescription opioid dependence have remained stable since 2005 (Addiction to Medicine, 2011). At least two distinct and overlapping populations of individuals who misuse prescription opioids likely coexist – those prescribed opioids, and those obtaining prescription opioids illicitly for the intent of euphoria or maintenance of a physical dependence. In the US and the UK, the majority of those who misuse prescription opioids are believed to have obtained them from their general practitioner directly or via friends and family, with sale on the illicit market, and internet sales representing significant but minor sources (Addiction to Medicine, 2011; NSDUH, 2009). The phenomenon of diversion has been called a “black box,” describing the uncertain means by which opioids are obtained, distributed and consumed non-medically (Inciardi, Surratt, Cicero, Kurtz, et al., 2009). Nonetheless, as opioid prescribing increases, physicians bear increasing public health responsibilities in their interactions with patients. Evidence from both the US and the UK shows that illicit prescription opioid use shares a market with heroin use (Inciardi, Surratt, Cicero, & Beard, 2009; Morgan, Griffiths, & Hickman, 2006), and thus the relative price and availability of each will affect rates of misuse. Although difficult to compare due to lack of control for purity, the World Drug Report 2012 indicates that the price of heroin is $62 per gram and $450 per gram in the UK and the US, respectively (UNODC, 2012). Although opioid agonist treatment, an evidence-based treatment for opioid dependence, continues to increase in the US (SAMHS, 2012), the more established and decentralized model of office and general practitioner-based provision of methadone and buprenorphine with the involvement of community pharmacists in the UK is likely better equipped to meet demand for services (Strang, Hall, Hickman, & Bird, 2010). There were 167,200 individuals in treatment for opioid use in England during 2009/2010 (Department of Health, 2010), 63% of an estimated 264,072 opioid users during that same time period (Hay, Gannon, Casey, & Millar, 2011). There were an estimated 600,000 individuals receiving opioid agonist treatment, 30% of an estimated 2 million opioid abusers in the US (SAMHSA, 2013). Both the relatively low price of heroin, and the availability of opioid agonist treatment may retard growth in the illicit market for prescription opioids in the UK. Lessons from drug poisoning data Although the number of opioid prescriptions has increased in both the US and the UK, England and Wales have not seen a concurrent rise in opioid overdose (see Fig. 2). One important methodologic challenge, however, is that surveillance and classification of cause of death are not standardized within or between countries; thus, precise comparison of opioid overdose rates is impossible. Several important trends have emerged in the analysis of overdose deaths in the US. First, misuse resulting from diversion was found to play a predominant role in unintentional opioid fatalities. In one study, less than half of overdose victims had ever been prescribed opioids, and 20% of overdose victims had obtained prescriptions from multiple physicians (Hall et al., 2008). Known as “doctor-shopping,” individuals in the US may take advantage of a decentralized physician network by securing multiple opioid prescriptions for themselves or for sale in the illicit market (Fischer, Bibby, & Bouchard, 2010). Oversight of such activity is complicated by regulations and surveillance networks that often differ across state lines. The single payer model of healthcare delivery and central regulatory body in the UK may limit “doctor-shopping.”

1126

D.F. Weisberg et al. / International Journal of Drug Policy 25 (2014) 1124–1130

Table 1 Definitions of misuse according to the DSM-IV, Chou et al., 2007; American Psychiatric Association, 1994; Substance Abuse and Mental Health Services Administration, 2013, the American Pain Society, and Substance Abuse and Mental Health Services Administration (Becker & Fiellin, 2012; Gourlay, Heit, & Almahrezi, 2005; Green et al., 2011). Dependence

Abuse Diversion Nonmedical use Aberrant drug-related behavior

Synonymous with addiction. A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period: 1. Tolerance, as defined by either of the following: a) A need for markedly increased amount of the substance to achieve intoxication or the desired effect or b) Markedly diminished effect with continued use of the same amount of the substance. 2. Withdrawal, as manifested by either of the following: a) The characteristic withdrawal syndrome for the substance or b) The same (or closely related) substance is taken to relieve or avoid withdrawal symptoms. 3. The substance is often taken in larger amounts or over a longer period than intended. 4. There is a persistent desire or unsuccessful efforts to cut down or control substance use. 5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects. 6. Important social, occupational or recreational activities are given up or reduced because of substance use. 7. The substance use is continued despite knowledge of having a persistent physical or psychological problem that is likely to have been caused or exacerbated by the substance. A maladaptive pattern of substance use manifested by recurrent and significant adverse consequences related to the repeated use of substances. Criteria differ from dependence in their lack of physiologic withdrawal or tolerance. The intentional transfer of a controlled substance from legitimate distribution and dispensing channels. Use of prescription drugs without a prescription or use that occurred simply for the experience or feeling the drug caused. A behavior inconsistent with an opioid treatment agreement established between prescriber and patient.

A disproportionately large percentage (31.4%) of opioid-related deaths in the US have been attributed to methadone prescribed for pain (Vital signs, 2012). Methadone implicated in overdose fatalities in one analysis was primarily due to diversion (67%) followed by prescription to the individual for chronic pain (33%), and finally for addiction (8%) (Madden & Shapiro, 2011). Methadone has been increasingly incorporated into chronic pain management in the US. However, the pharmacokinetic complexity of methadone and potential for increased risk have led some to question whether

Fatal Drug Poisonings Per 100,000 14

12

10

8

US

6

England and Wales 4

2

safe use in general practice for the treatment of chronic pain is possible (Lipman, 2005; Parran, 2010). In the UK, methadone is consumed at the same level per capita as in the US (DCAMC, 2012). However, unlike the US, methadone use for pain is limited in England, with only 2.7% of methadone prescriptions written for pain (HSCIC, 2011). The low level of methadone related deaths (Morgan et al., 2006) is likely due to supervised administration in the context of addiction treatment (Strang et al., 2010). Higher average daily doses of opioids have been found to increase risk of overdose (Bohnert et al., 2011). In addition, prescribed opioids carry risks when part of a regimen consisting of multiple drugs, common in elderly patients, that may have pharmacokinetic interactions, or exhibit synergistic side effects (Gallagher, 2001). Opioid overdose deaths in the US are often related to polysubstance use; notably, benzodiazepines, are often implicated with opioids in overdoses (Hall et al., 2008). Although when used alone benzodiazepines have a wide therapeutic index, potentially fatal respiratory depression occurs more readily with concurrent opioid and benzodiazepine use (Jones, Mogali, & Comer, 2012). In addition, the addiction potential of benzodiazepines and opioids may increase with concomitant use (Vogel et al., 2013). Although alternative treatments for anxiety and insomnia have more favorable safety and efficacy profiles (Buscemi et al., 2007; Uhlenhuth, Balter, Ban, & Yang, 1999), benzodiazepine prescriptions have been trending upwards in the US and the opposite trend has been observed in the UK, where the per capita rate of consumption is currently one fourth of that in the United States (Addiction to Medicine, 2011; EDVINUSPD, 2010; INCB, 2011).

0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Pharmaceutical industry and cultural influences in opioid misuse ˜ AM. Drug poisoning Fig. 2. 1. Warner M, Chen LH, Makuc DM, Anderson RN, Minino deaths in the United States, 1980–2008. NCHS data brief, no 81. Hyattsville, MD: National Center for Health Statistics. 2011. 2. Office for National Statistics (ONS). Number of deaths from drug-related poisoning or drug misuse by sex, underlying cause and age, England and Wales, 1993-2010. 2010. Available: www.ons.gov.uk. 3. US Census Bureau. Intercensal Estimates of the Resident Population by Sex and Age for the United States: April 1, 2000 to July 1, 2010. 2010. Available: www.census.gov. 4. Office of National Statistics. Population Estimates for UK, England and Wales, Scotland and Northern Ireland, Population Estimates Timeseries 1971 to Current Year. Available: www.ons.gov.uk.

Professional guidelines in the UK and US are largely in agreement in terms of recommendations for opioids for pain (Chou, 2009; The British Pain Society, 2010). However, the landscape of opioid treatment differs in these countries with approaches to health care delivery that are unique to their respective cultures and histories. Pharmaceutical company marketing practices in the US have served to inflate the benefits and obscure the harms of opioids.

D.F. Weisberg et al. / International Journal of Drug Policy 25 (2014) 1124–1130

1127

Table 2 Timeline of selected events influencing opioid prescribing and misuse: United States and United Kingdom. Year

In favor of increased opioid use

In favor of decreased opioid use

Early 1990s

Intractable Pain Treatment Acts (IPTA) brought to legislature in several states designed to protect physicians from prosecution when prescribing pain medicines for “intractable” pain

Uniform Controlled Substances Act: physicians are required to obtain a DEA registration number in order to prescribe schedule II drugs

1995

OxyContin, a time-release formulation of Oxycodone, marketed by Purdue Pharmaceuticals, approved by FDA

1996

James Campbell, president of the American Pain Society popularizes the notion of pain as a vital sign in order to promote assessment and treatment of pain

1997

California: Pain Patients Bill of Rights becomes state law. The use of opioids for chronic pain is emphasized American Academy of Pain Medicine and American Society of Anesthesiologists independently release guidelines calling for expanded use of opioids for chronic pain

2001

Joint Commission on Accreditation of Healthcare Organizations pain management standards go into effect

2003

Rush Limbaugh and Courtney Love publicly admit to prescription pain medication abuse

Article published in the New England Journal questions the safety of opioids in high doses and for long-term use

2004

House television series airs on the Fox network portraying a troubled but brilliant doctor who is addicted to pain medication

Dr. William Hurwitz convicted and sent to prison for inappropriate prescription of opioids for the treatment of chronic pain

United States

2006

Oklahoma launches its electronic Prescription Drug Monitoring Program to track patients and prescriber activity

2007

Purdue Pharmaceuticals pleads guilty to misbranding. Lawsuit alleged that the company downplayed the addictive potential of OxyContin in marketing the drug

2009

Florida begins a campaign to crack down on “Pill Mills”

2011

Washington State enacts a law requiring specialty referrals for patients taking pain medications above a threshold level

2012

FDA approves Risk Mitigation and Education Strategy (REMS) for long acting opioids, which will implement voluntary training programs for prescribers. The program is underwritten by drug manufacturers who will fund but not design the programs American Pain Foundation dissolves amidst controversy alleging pharmaceutical company marketing and lobbying under the guise of “patient advocacy”

2013

FDA mandates change in labeling for extended release opioid formulations. Change from “moderate to severe” pain to pain that is “severe enough” to require round the clock treatment

United Kingdom 1991

Regional Medical Officers no longer required to audit controlled substances in general practice

2000

Harold Shipman, General Practitioner, convicted for the murder of 15 of his patients

2004

“Recommendations for the appropriate use of opioids for persistent non-cancer pain” published. A consensus statement prepared on behalf of the Pain Society, the Royal College of Anaesthetists, the Royal College of General Practitioners and the Royal College of Psychiatrists

2005

Co-Proximal withdrawn from the UK market over concern for overdose and given lack of efficacy above paracetamol for acute pain

2006

Health Act of 2006 in response to Shipman Inquiry establishes “Accountable Officers”, local officials responsible for safe management of controlled drugs, monitoring systems by various authorities, and collaboration between responsible bodies on the local level

2007

All Party Parlimentary Drugs misuse group outline priorities in training, monitoring, and research in regard to prescription and over-the-counter medications

2012

Department of Health/Government round table group and consensus statement on addiction to medicines

Notably, Purdue Pharmaceuticals pleaded guilty to fraud charges over its marketing of OxyContin (Van Zee, 2009). Moreover, pharmaceutical companies appear to have undue influence among select pain advocacy groups. The American Pain Foundation

dissolved in 2012 amidst controversy that pharmaceutical companies fraudulently represented their interests under the guise of patient advocacy, supplying nearly 90% of foundation’s $5 million funding in 2010 (Weber, 2012).

1128

D.F. Weisberg et al. / International Journal of Drug Policy 25 (2014) 1124–1130

Advocacy groups, many with records untarnished by the pharmaceutical industry, were instrumental in improving the under-treatment of pain by empowering patients and influencing public policy; for example, in the late 1990s, the measurement of pain was equated to a “fifth vital sign,” and healthcare institutions were required to meet new standards of pain assessment and treatment (see Table 2). Critics point out that a culture of consumerism has developed in US medicine, reinforced by pharmaceutical company direct-toconsumer advertising (i.e., advertising of pharmaceutical products to the public on television, radio, print, social media, etc.), which is illegal in all other western countries except for New Zealand. Patients may expect quick fixes for complex problems such as pain, and may be unable to afford non-opioid therapies such as psychological or rehabilitative services. Physicians may be incentivized to provide opioid therapy, which has shown to be one of the few variables affecting patient satisfaction (Wallace, Freburger, Darter, Jackman, & Carey, 2009); while physicians in the US are financially incentivized to enhance patient satisfaction, there may be simultaneous disincentives to provide more complex, time consuming, and poorly compensated types of care (Lembke, 2012). At one extreme, some physicians take advantage of this climate and profit from opioid prescribing in schemes known as “pill mills” (Rigg, March, & Inciardi, 2010) wherein prescriptions are provided with perfunctory or absent physician–patient interactions. In the US, physicians have been prosecuted on charges of both excessive opioid prescribing and the under treatment of pain (see timeline). The influence of such lawsuits on prescribing practices is unclear, but one survey found that one third of physicians lowered dosage or did not prescribe schedule II opioids for fear of investigation (Wolfert, Gilson, Dahl, & Cleary, 2010). The payment structure of the National Health Service in the UK may reduce the rogue behavior described above such as pill mills. The private insurance industry in the UK is very small and represents only 0.1% of controlled substance prescribing (CQC, 2011). A search of the proceedings of the General Medical Council reveals that no cases regarding aberrant opioid prescribing in the treatment of pain have been brought up for review. In addition, no prominent lawsuits regarding the fraudulent marketing of opioids have been tried in the UK. Despite the centralized oversight afforded by a public health insurance system, studies from Canada suggest that this is not necessarily protective against prescription opioid misuse (Dhalla et al., 2009). Furthermore, the implementation of health care reform in the UK may decrease centralized surveillance of physicians and patients, potentially increasing the risk of inappropriate prescribing.

Forming opioid policies through regulation, surveillance, and education Analogous to States, which have a degree of autonomy in public health governance in the US, the devolved administrations of the UK (Scotland, Wales, and North Ireland) differ in meaningful ways with respect to public health priorities, as well as structural aspects of healthcare delivery. Moreover, it is important to acknowledge regional variations in opioid use and opioid-related harms in the US and the UK. Nevertheless, in both the US and the UK there is consistency in their respective approaches to clinical care and harm reduction in relation to opioid use for chronic pain and for management of addiction. Harold Shipman, a general practitioner found guilty of the murder of 15 of his patients with a further 250 murders ascribed to him, was the impetus for sweeping reform of regulation of opioid

prescribing in the UK. Shipman used opioids to kill his patients over many years. The Shipman trial and subsequent inquiry (Smith, 2004) led to reforms regarding the storage, distribution, and oversight of opioid prescriptions. The Health Act of 2006 created Accountable Officers, local individuals with authority to oversee all aspects of controlled drug prescribing. Among other duties, these officials monitor and audit opioid prescriptions in their jurisdiction. Prescription data can be accessed in real-time by select individuals on the newly developed “ePACT” system. Piloting the program, the Care Quality Commission reported that it was able to identify irregular prescribing of temazepam (SMCD, 2010). Although the ePACT system provides the framework for monitoring of controlled substances, its utility is limited by a significant lag time (approximately 2 months) between prescription dispensation and data availability, and is not currently used as part of clinical practice to monitor the behavior of individual patients (e.g., doctor-shopping). Likewise, it is not routinely employed to monitor the behavior of prescribers. The Health Act also recommended restrictions on the amount of opioids physicians can prescribe to individuals, setting a constraint of a 30-day supply and limiting the ability to fill opioid prescription to within 28 days of when it is written. In the US, the regulatory response to the epidemic of opioid misuse has primarily been state legislation, such as one state’s ceiling on allowable doses of opioids prescribed in general practice (McCarthy, 2012), restrictions on purchasing prescriptions over the internet (CASA, 2008), and federally supported prescription drug monitoring programs (PDMPs), which allow clinicians to track patients’ receipt of controlled substances through access to centralized patient prescription and pharmacy information with variable lag-time (from immediate to several weeks depending on the State) between prescription dispensation and data availability. PDMPs are thought to represent a key strategy in curbing opioid misuse (Perrone & Nelson, 2012). Studies of PDMPs’ effect on misuse have methodological challenges and outcomes have shown conflicting data regarding efficacy in reducing opioid overdose rates, opioid treatment admissions, or inappropriate prescribing (Dormuth, Miller, Huang, Mamdani, & Juurlink, 2012; Paulozzi, Kilbourne, & Desai, 2011; Reifler et al., 2012; Reisman, Shenoy, Atherly, & Flowers, 2009). Survey data indicate that these programs have utility in clinical practice and change management decisions (Baehren et al., 2010; Green et al., 2012). The rates of PDMP use vary widely among physicians, and depend on the type of program available in their state (43/50 states currently have operational PDMPs). Most states report that less than one quarter of physicians utilize PDMPs (Green, Zaller, Rich, Bowman, & Friedmann, 2011); two states, however, require checking a PDMP before prescribing opioid medications. Another important attempt to curb opioid misuse in the US is the FDA’s Risk Mitigation and Education Strategy (REMS), which mandates that pharmaceutical companies implement programs to train physicians in safe opioid prescribing. However, the program does not set goals for the number of physicians to be trained, and some point out the undesirable conflict of interest inherent in industry’s role in education regarding prescribing practices (Becker & Fiellin, 2012). “Universal Precautions” is a widely cited, safety-minded approach to the management of chronic pain with opioids, and includes risk stratification, the establishment of a treatment agreement, and routine assessment of the “4 As” of pain management (analgesia, activity, adverse effects, and aberrant behavior) (Gourlay, Heit, & Almahrezi, 2005). A study of primary care pain management in the US found that 64% of primary care physicians observed the major components of universal precautions in ≥75% of their patients (Brown et al., 2011).

D.F. Weisberg et al. / International Journal of Drug Policy 25 (2014) 1124–1130

1129

Discussion

Author information

The comparison between the US and the UK in opioid consumption and overdose rates should serve as a call to action for UK physicians and policymakers. The trends in decreasing benzodiazepine prescriptions and limited use of methadone for the treatment of chronic pain in the UK as well as structural elements of the National Health Service (NHS) may serve to buffer opioidrelated harms in the face of increasing prescriptions. In addition, the availability and price of heroin, as well as the ease of access to opioid agonist treatment in the UK may limit the growth of the illicit market for prescription opioids. Opioid policies in the US have sought to catch up with a widespread epidemic, and their efficacy has yet to be conclusively studied. Although further study is necessary in both the US and the UK, basic, proactive steps in the form of surveillance – of overdoses, marketing practices, prescribers, and patients – and education programs may help avert a public health crisis as opioid prescriptions increase. A first step involves standardizing the reporting of opioidrelated harms. Even within countries, jurisdictions do not reliably report drug poisonings in a standardized manner, confounding the task of surveillance. An international effort is underway to harmonize such reporting through the Global Toxicosurveillance Network (GTNet), a collaboration between the US, UK, Germany, Italy, Netherlands, Switzerland, and Australia, and this effort should be applauded and expedited in the name of accurately tracing prescription opioid misuse (RADARS system, 2012). As the US strengthens its prescription drug monitoring, investigates drug manufacturers (Baucus, 2012), and implements REMS, the UK should consider similar steps to strengthen the safety and quality of opioid prescribing. Expanded use of the ePACT system with improved lag-time between dispensation and data availability in the UK has the potential to alert regulators of aberrant prescribing behaviors, and provide clinicians data on undisclosed sources of prescription medications. In order to promote evidence-based prescribing practices, the UK can move beyond limitations of the REMS by implementing a universal prescriber education program and insulating educational programs from the pharmaceutical industry. In addition to targeting practicing physicians, comprehensive educational programs on safe opioid prescribing should be implemented in medical schools. Educational programs should highlight the dangers, as discussed above, of methadone prescribing for pain, high-dose regimens, and polypharmacy, including the concomitant use of benzodiazepines and opioids. In addition, these programs should include a framework for identifying and monitoring high-risk patients as well as provide alternative strategies in pain management. While education is not a panacea, it is a necessary component of effecting behavior change among providers and patients. The lessons from the comparison of opioid misuse in the US and the UK apply to all countries experiencing a rise in opioid use. Surveillance of opioid-related harms, support of evidence-based opioid prescribing through educational programs, and monitoring of aberrant prescribing are key strategies to promote appropriate and safe opioid use.

CS, DF and WB are clinicians and researchers with extensive experience in the area of opioid prescribing. In addition, CS served as the UK Chair of the Consensus Group and Editor of the British Pain Society’s and Medical Royal College’s guidance entitled “Opioids for Persistent Pain: Good Practice”, and DF has served on the White House Office of National Drug Control Policy (ONDCP), Drug Control Research, Data, and Evaluation Advisory Committee, and the World Health Organization and United Nations Office on Drugs and Crime Technical Guideline Development Group for psychosocially assisted pharmacologic treatment of opioid dependence.

Authors contributions DW performed the data analysis from national drug poisoning data from the United States and the United Kingdom as well as opioid consumption data compiled by the Drug Control and Access to Medicines Consortium (http://dcamconsortium.net/). DW wrote the first draft of the manuscript based on inter-continental discussions between the authors, and worked with CS, DF, and WB in revising it. All authors approved the final version of the manuscript.

Funding source Funds from The Office of International Medical Student Education, Yale University School of Medicine, supported this study. Dr. Fiellin is supported by a grant from the National Institutes on Drug Abuse, DA020576-01. Dr. Becker is supported by a Veterans Health Administration Health Services Research & Development Career Development Award (08-276). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the institutions with which they are affiliated. References Addiction to Medicine. (2011). The national treatment agency for substance misuse. www.nta.nhs.uk American Psychiatric Association. (1994). Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV (4th ed.). Washington, DC: American Psychiatric Association. Baehren, D. F., Marco, C. A., Droz, D. E., Sinha, S., Callan, E. M., & Akpunonu, P. (2010). A statewide prescription monitoring program affects emergency department prescribing behaviors. Annals of Emergency Medicine, 56(1), 19–23.e1–3 Baucus. (2012, May). Grassley Seek Answers about Opioid Manufacturers’ Ties to Medical Groups. United States Senate Committee on Finance. http://www. finance.senate.gov/newsroom/chairman/release/?id=021c94cd-b93e-4e4ebcf4-7f4b9fae0047,. Accessed 15.06.13 Becker, W. C., & Fiellin, D. A. (2012). Federal plan for prescriber education on opioids misses opportunities. Annals of Internal Medicine, 157(3), 205–206. Bohnert, A. S., Valenstein, M., Bair, M. J., et al. (2011). Association between opioid prescribing patterns and opioid overdose-related deaths. Journal of the American Medical Association, 305(13), 1315–1321. Brown, J., Setnik, B., Lee, K., Wase, L., Roland, C. L., Cleveland, J. M., Siegel, S., Katz, N., et al. (2011). Assessment, stratification, and monitoring of the risk for prescription opioid misuse and abuse in the primary care setting. Journal of Opioid Management, 7(6), 467–483. Buscemi, N., Vandermeer, B., Friesen, C., Bialy, L., Tubman, M., Ospina, M., Klassen, T. P., Witmans, M., et al. (2007). The efficacy and safety of drug treatments for chronic insomnia in adults: A meta-analysis of RCTs. Journal of General Internal Medicine, 22(9), 1335–1350. CASA (The National Center on Addiction and Substance Abuse at Columbia University). (2008, May). “you’ve got drugs!” V: Prescription drug pushers on the Internet [A CASA White Paper]. http://www.casacolumbia.org/addictionresearch/reports/youve-got-drugs-perscription-drug-pushers-internet-2008,. Retrieved 17.03.14 Centers For Disease Control and Prevention. Unintentional drug poisoning in the United States. http://www.cdc.gov/HomeandRecreationalSafety/ pdf/poison-issue-brief.pdf, 2010. Chou, R. (2009). Clinical Guidelines from the American Pain Society and the American Academy of Pain Medicine on the use of chronic opioid therapy in chronic noncancer pain: What are the key messages for clinical practice? Polskie Archiwum Medycyny Wewnetrznej, 119(7–8), 469–477. Chou, R., Fanciullo, G. J., & Fine, P. G. (2009). Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. Journal of Pain, 10, 113–130. Care quality commission: Annual report and accounts 2010/2011. www.cqc.org.uk, 2011. Drug Control and Access to Medicines Consortium. (2012). Opioid consumption chart. http://ppsg-production.heroku.com/chart,. Accessed 30.09.13 Department of Health. (2010). National Treatment Agency. Statistics from the National Drug Treatment Monitoring System (NDTMS) 1 April 2009–31 March 2010. Dhalla, I. A., Mamdani, M. M., Sivilotti, M. L., Kopp, A., Qureshi, O., & Juurlink, D. N. (2009). Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone. CMAJ: Canadian Medical Association journal, 181(12), 891–896. Dormuth, C. R., Miller, T. A., Huang, A., Mamdani, M. M., & Juurlink, D. N. (2012). Effect of a centralized prescription network on inappropriate prescriptions for opioid analgesics and benzodiazepines. CMAJ: Canadian Medical Association journal.

1130

D.F. Weisberg et al. / International Journal of Drug Policy 25 (2014) 1124–1130

(2010). Emergency department visits involving nonmedical use of selected prescription drugs – United States, 2004–2008. MMWR Morbidity and Mortality Weekly Report, 59(23), 705–709. Fischer, B., Bibby, M., & Bouchard, M. (2010). The global diversion of pharmaceutical drugsnon-medical use and diversion of psychotropic prescription drugs in North America: A review of sourcing routes and control measures. Addiction, 105(12), 2062–2070. Gallagher, L. P. (2001, November). The potential for adverse drug reactions in elderly patients. Applied Nursing Research, 14(4), 220–224. Gourlay, D. L., Heit, H. A., & Almahrezi, A. (2005). Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Medicine, 6(2), 107–112. Green, T. C., Zaller, N., Rich, J., Bowman, S., & Friedmann, P. (2012). Revisiting Paulozzi et al.’s “Prescription drug monitoring programs and death rates from drug overdose”. Pain Medicine, 13(10), 1314–1323. Green, T. C., Mann, M. R., Bowman, S. E., et al. (2012). How does use of a prescription monitoring program change medical practice? Pain Medicine. Hall, A. J., Logan, J. E., Toblin, R. L., Kaplan, J. A., Kraner, J. C., Bixler, D., Crosby, A. E., Paulozzi, L. J., et al. (2008). Patterns of abuse among unintentional pharmaceutical overdose fatalities. Journal of the American Medical Association, 300(22), 2613–2620. Hay, G., Gannon, M., Casey, J., & Millar, T. (2011). Estimates of the Prevalence of Opiate Use and/or Crack Cocaine Use, 2009/2010: Sweep 6 report. Home Office Online Report. http://www.nta.nhs.uk/facts-prevalence.aspx Health and Social Care Information Centre. (2011). Prescribing and primary care: Prescription cost analysis – England. http://www.ic.nhs.uk (04.04.12) International Narcotics Control Board. (2011). Psychotropic Substances: Statistics for 2011; Assessments of Annual Medical and Scientific Requirements for Substances in Schedules II, III and IV of the Convention on Psychotropic Substances of 1971 (E/INCB/2012/3). Inciardi, J. A., Surratt, H. L., Cicero, T. J., Kurtz, S. P., Martin, S. S., & Parrino, M. W. (2009). The “black box” of prescription drug diversion. Journal of Addictive Diseases, 28(4), 332–347. Inciardi, J. A., Surratt, H. L., Cicero, T. J., & Beard, R. A. (2009). Prescription opioid abuse and diversion in an urban community: The results of an ultrarapid assessment. Pain Medicine, 10(3), 537–548. Jones, J. D., Mogali, S., & Comer, S. D. (2012). Polydrug abuse: A review of opioid and benzodiazepine combination use. Drug and Alcohol Dependence, 125(1–2), 8–18. Kalso, E., Simpson, K. H., Slappendel, R., Dejonckheere, J., & Richarz, U. (2007). Predicting long-term response to strong opioids in patients with low back pain: Findings from a randomized, controlled trial of transdermal fentanyl and morphine. BMC Medicine, 5, 39. Lembke, A. (2012). Why doctors prescribe opioids to known opioid abusers. New England Journal of Medicine, 367(17), 1580–1581. Lipman, A. G. (2005). Methadone: A double edged sword. Journal of Pain and Palliative Care Pharmacotherapy, 19(4), 3–4. Lohman, D., Schleifer, R., & Amon, J. J. (2010). Access to pain treatment as a human right. BMC Medicine, 8, 8. Madden, M. E., & Shapiro, S. L. (2011). The methadone epidemic: Methadone-related deaths on the rise in Vermont. American Journal of Forensic Medicine and Pathology, 32(2), 131–135. McCarthy, M. (2012). Containing the opioid overdose epidemic. British Medical Journal, 345, e8340. Morgan, O., Griffiths, C., & Hickman, M. (2006). Association between availability of heroin and methadone and fatal poisoning in England and Wales 1993–2004. International Journal of Epidemiology, 35(6), 1579–1585. Noble, M., Treadwell, J. R., Tregear, S. J., et al. (2010). Long-term opioid management for chronic noncancer pain. Cochrane Database of Systematic Reviews, 1, CD006605. (2009). Results from the 2008 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NSDUH Series H-36, HHS Publication No. SMA 09-4434). Rockville, MD: Substance Abuse and Mental Health Services Administration.

Okie, S. (2010). A flood of opioids, a rising tide of deaths. New England Journal of Medicine, 363(21), 1981–1985. Parran, T. (2010). Methadone Dosing for pain and equi-analgesic tables. Prescribers’ Clinical SUpport System for Opioid Therapies, http://www.pcss-o.org/,. Accessed 24.01.13 Paulozzi, L. J., Kilbourne, E. M., & Desai, H. A. (2011). Prescription drug monitoring programs and death rates from drug overdose. Pain Medicine, 12(5), 747–754. Perrone, J., & Nelson, L. S. (2012). Medication reconciliation for controlled substances – An “ideal” prescription-drug monitoring program. New England Journal of Medicine, 366(25), 2341–2343. RADARS system Newsletter, http://www.radars.org, 2012. Reifler, L. M., Droz, D., Bailey, J. E., et al. (2012). Do prescription monitoring programs impact state trends in opioid abuse/misuse? Pain Medicine, 13(3), 434–442. Reisman, R. M., Shenoy, P. J., Atherly, A. J., & Flowers, C. R. (2009). Prescription opioid usage and abuse relationships: An evaluation of state prescription drug monitoring program efficacy. Substance Abuse: Research and Treatment, 3(SART3-Shenoy-et-al), 41. Rigg, K. K., March, S. J., & Inciardi, J. A. (2010). Prescription drug abuse & diversion: Role of the pain clinic. Journal of Drug Issues, 40(3), 681–702. Substance Abuse and Mental Health Services Administration. (2012). National Survey of Substance Abuse Treatment Services (N-SSATS): 2011. Data on Substance Abuse Treatment Facilities, BHSIS Series: S-64, HHS Publication No. (SMA) 12-4730. Rockville, MD: Substance Abuse and Mental Health Services Administration. Substance Abuse and Mental Health Services Administration. (2013, April). Center for behavioral health statistics and quality. The N-SSATS report: Trends in the use of methadone and buprenorphine at substance abuse treatment facilities: 2003–2011. Rockville, MD. Safer Management of Controlled Drugs: Annual Report 2010. Care Quality Commission 2010. Smith, J. (2004). Fourth report: The regulation of controlled drugs in the community. The Shipman Inquiry, http://wwwshipman-inquiryorguk/reportsasp Strang, J., Hall, W., Hickman, M., & Bird, S. M. (2010). Impact of supervision of methadone consumption on deaths related to methadone overdose (1993–2008): Analyses using OD4 index in England and Scotland. British Medical Journal, 341, c4851. Substance Abuse and Mental Health Services Administration. (2013). Center for Behavioral Health Statistics and Quality. In The NSDUH Report: State Estimates of Nonmedical Use of Prescription Pain Relievers. Rockville, MD. The British Pain Society. (2010). Opioids for persistent pain: Good practice. http://wwwbritishpainsocietyorg/pub professionalhtm-opioids TOP 200 products of 2011 by total prescriptions. http://www.pharmacytimes.com/ media/ pdf/Top 200 Drugs 2011 Total Rx.pdf. Accessed 04.02.12. Uhlenhuth, E. H., Balter, M. B., Ban, T. A., & Yang, K. (1999). Trends in recommendations for the pharmacotherapy of anxiety disorders by an international expert panel, 1992–1997. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 9(Suppl. 6), S393–S398. UNODC, World Drug Report 2012 (United Nations publication, Sales No. E.12.XI.1). Van Zee, A. (2009). The promotion and marketing of oxycontin: Commercial triumph, public health tragedy. American Journal of Public Health, 99(2), 221–227. (2012). Vital signs: Risk for overdose from methadone used for pain relief – United States, 1999–2010. MMWR Morbidity and Mortality Weekly Report, 61(26), 493–497. Vogel, M., Knopfli, B., Schmid, O., et al. (2013). Treatment or “high”: Benzodiazepine use in patients on injectable heroin or oral opioids. Addictive Behaviors, 38(10), 2477–2484. Wallace, A. S., Freburger, J. K., Darter, J. D., Jackman, A. M., & Carey, T. S. (2009). Comfortably numb? Exploring satisfaction with chronic back pain visits. Spine Journal: Official Journal of the North American Spine Society, 9(9), 721–728. Weber, T. O., & Charles. (2012 May). Senate panel investigates drug companies’ ties to pain groups. Washington Post, 8, 2012. Wolfert, M. Z., Gilson, A. M., Dahl, J. L., & Cleary, J. F. (2010). Opioid analgesics for pain control: Wisconsin physicians’ knowledge, beliefs, attitudes, and prescribing practices. Pain Medicine, 11(3), 425–434.