by J. Lance LaFleur, MD, MBA
“If we know that severe pain and suffering can be alleviated and we do nothing about it, we, ourselves, are tormentors.”
It is difficult to overestimate the stakes of the accurate management of pain. Left undiagnosed and untreated, the headache after subarachnoid hemorrhage or the arm pain from myocardial infarction or chondrosarcoma could very well be lethal. When the pain is not only a symptom, but a disease state, the diagnostic and treatment quandaries remain. Unfortunately, the use of opioids, one of the historic mainstays of therapy for the chronic pain patient, is becoming increasingly complex.
Approximately 8% of Americans with immense suffering, who are often confined to their homes because of severe, disabling pain, comprise part of the total 37% in our nation with chronic pain.1 The cost of medical treatment for patients with chronic pain in the U.S. is in excess of $100 billion annually.2
Current treatment paradigms employed by fellowship trained, board-certified interventional pain physicians are both comprehensive and multidisciplinary. They often include rehabilitation approaches (e.g., assistive devices and physical or aquatic therapy), lifestyle changes, adjuvant analgesics and opioids, psychological and psychiatric approaches (e.g., cognitive behavioral therapy and transcranial magnetic stimulation), spine and joint injections, and radiofrequency ablation of nerves. Some patients with severe, refractory pain may be appropriate candidates for a trial of neuromodulation including spinal cord stimulation or intrathecal drug delivery.
Along with our growing chronic pain population, we are facing a global epidemic of opioid abuse, addiction, and related mortalities. Worldwide, there is more prescription drug abuse than heroin, cocaine, and ecstasy combined.3 Deaths due to prescription overdoses are now more common than motor vehicle fatalities in the U.S., and more patients present to emergency departments for prescription drug abuse than for illicit drug use.4 Thus, it is clear that we have a legitimate prescription drug crisis, and we desperately need to improve our understanding and management of opioid prescribing and abuse.
Prior to the 1990s, opioids were prescribed more conservatively for chronic, non-cancer pain, and appropriately more liberal for cancer pain. By the late 1990s, researchers and physician leaders began to support the use of opioids for chronic, non-cancer pain. They cited extremely low addiction rates around 1%, and they felt strongly that pain was vastly undertreated and opioids were underutilized. Even as opioid overdoses, diversion, and crime paralleled increasing opioid prescriptions, they considered these to be law enforcement challenges which should not influence medical practice.
The right to pain relief movement and surging opioid use continued to gain support from a variety of sources. State medical boards relaxed their opioid restrictions and disciplinary positions for physicians which led to further increases in opioid prescribing. In 1999, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) declared pain to be the “fifth vital sign,” as they concluded that widespread undertreated pain worsened outcomes and increased healthcare costs.5 Then, in 2000, Congress passed and the President signed a law that began the Decade of Pain Control and Research on January 1, 2001. Reputable national pain organizations including the American Pain Society (APS) and the American Academy of Pain Medicine (AAPM) published revised position statements in support of chronic opioid therapy. The term “opiophobia” was coined by some of the thought leaders to describe physicians withholding these valuable medicines leading to inadequate treatment of their pain patients. Removing the stigma from opioids was paramount to their burgeoning mission.
As the swinging pendulum gained momentum in favor of chronic opioid therapy for chronic non-cancer pain, the pharmaceutical industry took notice. Several new opioids were released, heavily marketed, and wildly successful. Their efficacy was exaggerated, their risks were minimized, and their indications were expanded. From 1999 to 2010 in the U.S., prescription analgesic sales quadrupled, and the number of overdose deaths from these drugs quadrupled as well.6,7 Enough opioids were sold that every adult in the U.S. could receive 15 mg of hydrocodone daily for 47 days.8 Currently, the U.S. comprises 5% of the world’s population, but consumes 99% of the global hydrocodone production, 80% of the global oxycodone production, and approximately half of the worldwide production of methadone, hydromorphone, fentanyl, and meperidine.9
With prescribing habits altered and the liberalization of opioids widespread, opioid-related deaths and treatment admissions closely paralleled climbing opioid sales. In 2006, recreational use of prescription analgesics cost U.S. taxpayers $53.4 billion. This included $42 billion in job productivity, $8.2 billion in law enforcement and legal costs, $2.2 billion for addiction treatment, and $944 million in medical treatment.10
The identification and termination of “pill mills” which indiscriminately prescribe opioids and other high-risk analgesics has become a priority of law enforcement in many U.S. cities. These unscrupulous businesses often breed enormous levels of drug diversion. Although some pill mills may advertise as pain clinics, in reality, the only commonality is that they both prescribe opioids. True pain clinics offer thoughtful, comprehensive care for their patients, while pill mills only trade prescription drugs for cash. Unfortunately, Houston has had more than its fair share of pills mills. In fact, the combination of hydrocodone, Xanax, and Soma has been dubbed the “Houston cocktail.”
So, is it rational that opioids continue to exist in our pain armamentarium? As with most treatments in medicine, patient selection for chronic opioid therapy is critical. After all, in the chronic pain population, 40% misuse opioids, which is the use of a prescribed medication other than as directed. 20% of these patients abuse opioids, which refers to the use of a prescribed drug for a non-medical purpose or the use of an illegal drug. Lastly, 2-5% of these patients are addicted to their prescribed opioids, which is characterized by impaired control, compulsive use, harmful behaviors, and craving.
Several pain organizations, including the American Society of Interventional Pain Physicians (ASIPP), have recently published opioid prescribing guidelines. ASIPP’s 2012 “Guidelines for Responsible Opioid Prescribing in Chronic Non-Cancer Pain: Part I – Evidence Assessment” states that there is good evidence for the following: non-medical use of opioids is widespread and often coexists with illicit drug use; opioid prescriptions are increasing rapidly with the majority from non-pain physicians; risk factors for opioid-related death include several co-morbidities, higher doses and quantities, and doctor shopping; regarding opioid-related deaths, 60% were prescribed within the guidelines, and 40% occurred in 10% of drug abusers. Fair evidence exists for the efficacy of short-term opioids, but the data for long-term efficacy is limited due to a lack of high quality studies. Finally, there is fair evidence that no difference in efficacy is seen in long-acting versus short-acting opioids.11
ASIPP’s 2012 “Guidelines for Responsible Opioid Prescribing in Chronic Non-Cancer Pain: Part 2 – Guidance” provides recommendations for chronic opioid therapy over 90 days. They reported good evidence for the following: comprehensive medical evaluation including psychosocial, psychiatric, and substance abuse history prior to opioid initiation; baseline and intermittent urine drug testing (UDT); determine medical necessity and, when possible, diagnose physical and psychological disorders prior to opioid initiation; use caution whenever ordering diagnostic evaluations which may amplify fear and catastrophizing; discuss and document appropriate goals of opioid treatment; exercise particular caution with long-acting opioid titration and abuse; inquire about constipation and initiate a bowel regimen as soon as necessary. They found good to fair evidence for the use of prescription drug monitoring programs to curb doctor shopping and drug abuse. Lastly, there is fair evidence for the following: less than 40 mg of morphine equivalent is considered low dose, 41 to 90 mg of morphine equivalent is moderate dose, and over 91 mg of morphine equivalent is high dose; patients receiving methadone should have an electrocardiogram prior to the initiation of therapy, at 30 days, and annually thereafter.12
An essential monitoring tool for the opioid patient is urine drug testing. This provides data for compliance with therapy when the prescribed drug is identified. It also identifies noncompliant patients with either the absence of prescribed drug or the presence of nonprescribed or illicit drugs. UDT typically involves a screening immunoassay followed by a confirmatory chromatography and mass spectrometry analysis. The Texas Pain Society has recently published their UDT policy which supports a risk assessment with the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) prior to initiating chronic opioid therapy. SOAPP-R results are used to risk stratify patients into low, moderate, and high risk. All patients should undergo baseline UDT and random UDT based on their risk profile. Low risk patients should be sampled 1-2 times per year, moderate risk 3-4 times per year, and high risk 4 times per year to every office visit. Importantly, risk profiles may change based on UDT results, aberrant behaviors, and family insights.13
One significant result of the opioid epidemic is the recent request by the U.S. Drug Enforcement Administration (DEA) that an FDA advisory panel review the controlled substance classification of hydrocodone combination products (HCPs). Hydrocodone alone is currently a schedule II drug, but HCPs such as Lortab and Norco are schedule III. The FDA committee voted in favor of a recommendation to reschedule HCPs from schedule III to schedule II. This proposed rule has not been finalized. Also, until recently, there were no approved hydrocodone single-entity products. However, in October 2013, the FDA approved Zohydro ER which is a hydrocodone single-entity schedule II product. This decision sparked intense discussion as the drug lacks abuse-deterrent formulations.
Although opioids have migrated down our algorithm for chronic use in patients failing other more conservative therapies, many patients are grateful for the substantial pain relief that these medications provide. Proper patient selection, adherence monitoring, and multi-modal approaches to pain control may allow for the successful use of opioids. We need to maintain a vigilant stance on the high-risk contents of America’s medicine cabinets, and we should continue to identify the wayward prescribers and coordinate treatment for the addicts.