Facing the challenge of pain management and opioid misuse, abuse and opioid-related fatalities

KEYWORDS:

• Chronic pain
• opioids
• misuse
• abuse
• overdose
• IOM

It has been estimated that approximately one-third of the American population experience chronic or recurrent pain [1,2] with this number increasing each year as the baby boomers age. Effective pain management should be balanced and multimodal, including, in some cases, the use of opioid analgesics. There has been a growing controversy, however, over both the efficacy and the safety of opioid analgesics in managing patients with chronic pain.

The opioid pendulum

Historically, there have been extreme policies and philosophies regarding the use of opioids. In the 19th century, opioids were essentially unregulated. Commencing in the early 20th century, opioids were tightly regulated to the extent that if a physician prescribed maintenance opioids to an individual with an opioid addiction they would be censored and in some cases incarcerated, as addiction was not considered a disease. Even the prescription of opioids for painful medical conditions was restricted. Over time, it became recognized that opioids could be highly effective in managing acute pain and was accepted as appropriate for patients with cancer-related pain and for end-of-life care. Subsequently, strong advocacy efforts from grass root organizations (some funded by the pharmaceutical industry) in conjunction with the publication of several pivotal articles [3–5] suggested that legitimate pain patients, including those with chronic noncancer pain (CNCP), were at low risk for developing an opioid use disorder (OUD) and that patients were being deprived of adequate pain relief. The pendulum swung again to a clinical mind-set that patients with all types of pain (acute, CNCP, and end-of-life) were being undertreated and that clinicians should be more proactive in alleviating pain and suffering, which included the more liberal prescribing of opioids, often long term and at high doses. This led to a dramatic increase in the sales [6] and use of opioid analgesics [7]. For example, by 2004, the United States consumed 99% of the global supply of hydrocodone [8]. This escalation in opioid availability paralleled a corresponding increase in opioid-related fatalities [9] and admissions to treatment facilities for OUDs [10].

While a subgroup of carefully selected patients may benefit from the use of opioids with nominal risk or adverse effects, there is convincing evidence that the prevalence of prescription opioid misuse and abuse in patients with chronic pain is not inconsequential. Obtaining accurate estimates, however, has been challenging. Based on the prevailing literature, estimates of prescription opioid misuse and abuse range widely from <1% up to 40% [11–13] due to the inherent difficulty in diagnosing misuse, abuse, and OUD in the pain population and the lack of consistent definitions of misuse and abuse across studies [14]. There have been a number of attempts to more clearly define these terms. An expert panel (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks [ACTTION]) was convened and completed a systematic review of the literature and rendered recommendations for classifying and defining misuse and abuse [15]. Using the more refined definitions provided by ACTTION and another expert panel (initiative on methods, measurement, and pain assessments in clinical trials), Vowles et al. [16] conducted a systematic review of the literature and discovered that the rate of misuse ranged from 21.7% to 29.3% and OUDs from 7.8% to 11.7% in the pain population. Another study employed the more sensitive DSM-5 criteria for diagnosing OUD in a large cohort of patients with CNCP receiving opioid therapy. The results revealed that the prevalence of lifetime OUD was 34.9% and that 21.7% of this population met criteria for moderate OUD and 13.2% for severe OUD [17]. In a more recent study, again using the more sensitive DSM-5 criteria, it was discovered that in a cohort of patients with CNCP receiving long-term opioid therapy, 41.3% met criteria for a lifetime prevalence of any OUD [18]. These studies underscore that there is serious problem of opioid misuse and abuse in the pain population being prescribed opioid analgesics.

The key question then is how do you balance the risks and potential benefits of opioid therapy in suitable patients?

Risk assessment and monitoring

Risk assessment and monitoring includes (a) clinical interview (past medical history with special attention to effects of opioids or illnesses suggestive of substance abuse, pain characteristics, and consequences); (b) query prescription drug monitoring program if available and/or review of past medical records; (c) administering validated risk assessment tools (e.g. Opioid Risk Tool [19] or the Screener and Opioid Assessment for Patients with Pain [20]); (d) initial urine drug screening; (e) sleep disorder screening; and (f) mental health screening [21].

Risk mitigation strategies

A number of risk mitigation strategies have been developed including the following:

1. Limiting upper dosing thresholds: A number of published articles have demonstrated that the risk of opioid misuse, abuse, and opioid-related mortalities was directly related to the maximum daily opioid dose. Many state medical boards have issued opioid prescribing guidelines that set a recommended maximum daily opioid dose for patients with CNCP.

2. Abuse deterrent opioid formulations: The majority of long-acting opioid formulations have been reformulated with abuse deterrent technology to reduce the potential for misuse and abuse. Several studies have demonstrated a reduction in the abuse of Oxycontin with the new abuse deterrent formulation but a subset of patients just transitioned to other opioids, including heroin [22]. Also, this technology is not used in short-acting opioid preparations which are the most commonly abused.

3. Screening for absence of prescribed opioid, other prescription and nonprescription substances, and sleep-disordered breathing: Many opioid-related fatal and nonfatal opioid overdoses are polysubstance in nature, typically when opioids are prescribed in combination with benzodiazepines or other prescribed or nonprescribed central nervous system (CNS) depressants (alcohol, hypnotics, etc.) and especially in patients with sleep-disordered breathing (Obstructive Sleep Apnea, Central Sleep Apnea). Patients on long-term opioids should be routinely screened through urine drug monitoring for other prescribed and nonprescribed substances and if on high dosing of opioids or a patient is at risk for sleep-disordered breathing, a sleep study should be obtained.

4. Opioid Prescribing Guidelines: A number of expert consensus guidelines for opioid prescribing have been published to aid clinicians to mitigate the risks of opioids while preserving access to the benefits of opioids to appropriate patients. The majority of published guidelines had common recommendations, including limiting opioid dosing, judicious use of methadone, awareness of drug–drug and drug–disease interactions, and the potential efficacy of risk assessment tools, treatment agreements, and urine drug monitoring.

5. Prescription Drug Monitoring Programs: The majority of states have developed prescription drug monitoring programs which allow clinicians to access a state database on patient prescriptions. This helps determine if there is evidence of doctor shopping and receiving multiple opioid prescriptions and/or other potentially lethal medications if used in conjunction with opioids (benzodiazepines, hypnotics, and sedatives).

There is evidence that implementation of risk assessment and mitigation strategies along with a heightened awareness by clinicians of the potential deleterious effects of opioids has led to a plateau or decline in diversion and abuse of prescription opioids in recent years [23].

Barriers to effective pain management

The Institute of Medicine 2011 report ‘Relieving pain in America: a blueprint for transforming prevention, care, education and research’ [24] while recognizing that there was a serious problem of prescription opioid abuse also outlined several other important principles to guide the transformation of pain care, which included the following:

• Effective pain management is a ‘moral imperative’.

• Pain should be considered a disease with distinct pathology.

• There is a need for interdisciplinary treatment approaches.

• The effectiveness of pain treatment depends on a strong clinician–patient relationship.

A number of barriers need to be overcome to fully bring to fruition the changes in pain care necessary to improve the quality of life in the countless number of individuals who suffer from pain, while also reducing the risk of opioid misuse and abuse. Primary barriers are discussed in the following sections.

Reimbursement and access to non-opioid therapy

Individuals suffering from pain tend to be very complicated in nature, often presenting with various medical and psychiatric comorbidities that by nature necessitate a comprehensive approach. The new draft opioid guidelines from the Centers for Disease Control and Prevention state, ‘nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain.’ However, access to non-opioid alternatives such as cognitive behavioral therapy or psychotropic management by a skilled psychiatrist is generally inadequate due to relatively poor reimbursement for these types of services and for cognitive medicine in general. This complex patient population is best served with an interdisciplinary approach with a core group of health-care providers, which possess unique and complementary skills and have shared treatment philosophies and goals. Interdisciplinary pain care is the gold standard and has been demonstrated to be clinically and economically efficacious, and minimizing iatrogenic harm [25]. Unfortunately, due to our reimbursement system, the number of these clinics in the United States has dwindled to a scarce few, whereas they have burgeoned in other developed countries [26].

At the provider level, beleaguered clinicians who are being asked to care for more patients and ensure patient satisfaction which can determine reimbursement by default have relied upon opioids for CNCP. At the patient level, opioids while having analgesic properties also possess anxiolytic, hypnotic, and hedonic effects that may promote misuse by patients attempting to better control their mood, anxiety, and/or sleep as they do not have access to alternative care.

Training

The majority of pain care is delivered by primary care providers who typically are woefully undertrained or not trained in the basics of pain medicine. In both Canada and the United States, veterinarians receive more instruction in pain medicine than their medical counterparts. Likewise, addiction medicine is underrepresented in medical school curriculum. We cannot improve pain care and curb the misuse and abuse of opioids unless there is a revamping of medical school curriculums, and we treat both pain and addiction as primary diseases that deserve adequate attention.

Conclusion

With the national attention focused on the opioid ‘epidemic’, have we lost sight of one of the basic tenets of medicine: to relieve human suffering? There is no doubt that the staggering increase in prescription opioid misuse, abuse, and opioid-related mortalities paralleled the increase in the sales and availability of prescription opioids. Likewise, there is persuasive evidence that there are a number of non-opioid therapies that are equally efficacious if not superior to opioids (with lower risk profiles) for the majority of painful conditions. However, in a subgroup of patients who either have not responded to non-opioid pharmacotherapies and/or do not have access to alternative non-opioid, nonpharmacologic therapies, opioids may be the only avenue to relief their suffering and improve their quality of life. When opioids are a treatment option, the challenge of mitigating risk of opioid abuse and improving an individual’s quality of life comes down to appropriate patient selection. Making the right decision depends on time with the patient, experience, and training, most of which is missing in the current health-care environment.

True pain care reform is desperately needed from basic pain medicine training in medical, nursing, and dental schools and residency programs to overhauling the reimbursement system to a value-based system that would encourage a more holistic and evidence-based approach to chronic pain. Hopefully, we will not throw out the baby with the bathwater and be so focused on the opioid ‘epidemic’ and become so opioid phobic that we do not relieve suffering in the appropriate patient and miss the greater opportunity to accept the challenges outlined by the Institute of Medicine and actually reform pain care.

Financial and competing interests disclosure

MD Cheatle would like to acknowledge the support from Grant 1R01DA032776-01 from the National Institute on Drug Abuse, National Institutes of Health in the writing of this manuscript. MD Cheatle has affiliations with Cordant Healthcare, Campbell Alliance, Pernix, Nektar. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.