The new CDC opioid-prescribing guidelines¹ along with the recent FDA changes to include box warnings on immediate-release opioids have certainly garnered a large degree of attention and discussion from several groups, including physicians, patients, and pharmaceutical companies. Opioid dependence, addiction, and overdose are not new, but they have significantly escalated to epidemic proportions over the past 15 years. This has been highlighted in the news, with added media attention to unexpected deaths of persons of public notoriety and fame. However, the rampant increase in addiction and overdose is seen in all populations across the country, with some communities facing this dilemma at this scale for the first time in decades.

In an attempt to improve assessment and pain management in the mid to late 1990s, the concept of pain as the “fifth vital sign” was developed. This created a new paradigm in healthcare with newly imposed requirements from accreditation organizations to perform pain assessments and address pain management at all visits. Limited data existed regarding opioid effectiveness for chronic pain and the addictive nature of these medications. Additionally, the vigorous marketing of long-acting opioids to clinicians may have given some a false sense of comfort without fully understanding the risks as well as the benefits. Clinicians were under pressure to ensure adequate assessment and treatment of pain in a system of increasing demands, increasing complexity of patients, and increasing time constraints in patient encounters. Now, 15 years later, we are faced with the unexpected consequences of overuse of opioids with increased risk of addiction, overdose, and death.

The CDC guidelines attempt to provide a framework or a tool for clinicians in practice to address treatment of chronic pain in adults. It excludes the treatment of chronic pain in the context of cancer pain, palliative care, or end-of-life care. The goal is to improve patient care and safety and minimize the risk for adverse patient outcomes, such as addiction, overdose, and death. The CDC performed a systematic review with input from experts and organizations to inform these guidelines, but with an understanding that the evidence is limited and more studies are needed.

The guidelines include 12 recommendations with three fundamental principles:

1. Nonopioid pharmacologic therapy and nonpharmacologic therapy (ie, exercise therapy, weight loss, cognitive behavioral therapy, and sleep interventions) are preferred for chronic pain.
2. If opioids are necessary, the lowest possible effective dose should be prescribed (“start low and go slow”). Risks for opioid addiction and overdose increase significantly above 50 morphine milligram equivalents (MME), and doses above 90 MME should be avoided if possible.
3. If opioids are given, clinicians should monitor patients closely; avoid concurrent benzodiazepines; use state prescription drug–monitoring programs for decision-making for initiation and continuation; and use urine drug testing before and during therapy.

Overall, the 12 guidelines review the initiation, monitoring, dosage, and discontinuation of opioid use and the evaluation of risks and harms before and during therapy. They do not explicitly state that a controlled-substance contract should be documented with all patients; however, contracts are increasingly used in practice, and these guidelines can provide additional input for pain contracts and establish clear goals.

One guideline that may elicit controversy recommends that clinicians consider prescribing naloxone when a patient is identified as at increased risk for opioid overdose (that is, the patient has a history of overdose, history of substance use disorder, high opioid doses, or concurrent benzodiazepine use). As I read this guideline, the I think that the question needs to be asked whether a patient at high risk should even receive opioids. In many practices, high-risk patients are usually not prescribed opioids, especially for chronic use. In an acute condition that truly warrants opioid treatment, clear expectations of usage are discussed with the patient, and the lowest dosage, shortest duration, and a small pill count are prescribed. As a clinician, prescribing naloxone proactively is a new consideration for me. I can see the pros and the cons, and the benefit may outweigh the harm. Some may see it as a bold public health harm-prevention intervention like providing clean needles to patients addicted to IV drugs or as benign as prescribing a short course of steroids for patients with asthma to keep at home as part of an action plan.

I am concerned that this practice recommendation does not address the deeper issue of identifying patients at risk and patients with substance use disorders. It fails to confront the necessity for practice resources to effectively treat these patients. These resources include integrated behavioral and mental health providers, who can provide point-of-care services with the medical visit and receive proper payment for services, and accessible, integrated communication across all electronic health records (EHR) systems.

The epidemic of opioid overuse, addiction, and death is alarming, and certainly these guidelines, along with the FDA box warnings for both immediate and long-acting opioids, are a step in the right direction to combat this problem. I do not believe this will solve the issue. We need widespread public campaigns and education in all communities with increased awareness of the risks and harms. We must advocate for increased payment and support for behavioral health providers and clinicians who provide care to at-risk, vulnerable populations. Clinicians also need support and training to handle the complexities that arise with caring for patients with chronic pain. We need effective care coordination, support, and evidence-based methods to ensure appropriate management that creates a balanced approach and avoids the pendulum swing to significant under-treatment or non-treatment of chronic pain in our patients.

Reference

1. Frieden TR, Houry D. Reducing the Risks of Relief—The CDC Opioid-Prescribing Guideline [published online March 15, 2016]. N Engl J Med. doi: 10.1056/NEJMp1515917.
   

   ---

   In a continuing effort to educate prescribers and patients about the potential risks related to opioid use, the U.S. Food and Drug Administration today announced required class-wide safety labeling changes for immediate-release (IR) opioid pain medications. Among the changes, the FDA is requiring a new boxed warning about the serious risks of misuse, abuse, addiction, overdose and death. Today’s actions are among a number of steps the agency recently outlined in a plan to reassess its approach to opioid medications. The plan is focused on policies aimed at reversing the epidemic, while still providing patients in pain access to effective relief.

   The FDA is also requiring several additional safety labeling changes across all prescription opioid products to include additional information on the risk of these medications. This is part of the agency’s overall effort to help inform prescribers about the importance of balancing the serious risks of opioids with their role in managing pain.

   “Opioid addiction and overdose have reached epidemic levels over the past decade, and the FDA remains steadfast in our commitment to do our part to help reverse the devastating impact of the misuse and abuse of prescription opioids,” said Robert Califf, M.D., FDA commissioner. “Today’s actions are one of the largest undertakings for informing prescribers of risks across opioid products, and one of many steps the FDA intends to take this year as part of our comprehensive action plan to reverse this epidemic.”

   Opioid analgesics are powerful pain-reducing medications that include prescription oxycodone, hydrocodone and morphine, among others. Prescription opioids are divided into two main categories – IR products, usually intended for use every four to six hours; and extended-release/long-acting (ER/LA) products, which are primarily intended to be taken once or twice a day, depending on the individual product and patient. Certain opioids, such as methadone and buprenorphine, are also used as a form of treatment for opioid addiction, and in combination with behavioral therapy and counseling, are known as medication-assisted treatment, or MAT.

   The updated indication clarifies that because of these risks, IR opioids should be reserved for pain severe enough to require opioid treatment and for which alternative treatment options (e.g., non-opioid analgesics or opioid combination products, as appropriate) are inadequate or not tolerated. The dosing information also provides clearer instructions regarding patient monitoring and drug administration, including initial dosage, dosage changes during therapy and a warning not to abruptly stop treatment in a physically dependent patient.

   As part of the boxed warning on IR opioid analgesics, the FDA now requires a precaution that chronic maternal use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS), which may be life-threatening if not recognized and treated using protocols developed by neonatology experts. NOWS may occur in a newborn exposed to opioid drugs for a prolonged period while in utero.

   In 2013, the FDA required class-wide labeling changes for ER/LA opioid analgesics that included modifications to the products’ indications, limitations of use, and warnings, including boxed warnings to more effectively communicate to prescribers the serious risks associated with these drugs. Today, the FDA is requiring similar changes to the labeling of IR opioid analgesics.

   “We know that there is persistent abuse, addiction, overdose mortality and risk of NOWS associated with IR opioid products,” said Douglas Throckmorton, M.D., deputy center director of regulatory programs, FDA’s Center for Drug Evaluation and Research. “Today, we have taken an important next step in clarifying and making more prominent the known risks of IR opioid medications.”

2. Additionally, the FDA is requiring updated labeling for all opioids (both ER/LA and IR products) to include safety information about potentially harmful drug interactions with other medicines that can result in a serious central nervous system condition called serotonin syndrome. Updated labeling will also include information about opioid effects on the endocrine system, including a rare but serious disorder of the adrenal glands (called adrenal insufficiency) and decreased sex hormone levels (androgen deficiency). These labeling changes will also make it clear that these negative outcomes can occur whether a patient is taking an opioid to treat pain or if the product is being used for MAT. Today, the FDA issued aDrug Safety Communication outlining these risks.

   “The broad set of actions announced today is reflective of the FDA’s efforts to improve informed prescribing of opioids across the board,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “We have been and will continue to evaluate all new data to ensure that labels of opioid drugs contain appropriate prescribing information about the benefits and risks of prescription opioids.”

   The FDA is also aware of, and carefully reviewing, available scientific information about potentially serious outcomes related to interactions between benzodiazepines and opioids. Once a review of all available scientific information is completed, the FDA will take necessary actions to ensure prescribers and the public are informed of the risks involved with the use of these medications.

These actions are the latest examples of the agency’s commitment to combat this public health crisis and its profound impact on individuals, families and communities across our country. Health and Human Services Secretary Sylvia M. Burwell has made addressing opioid misuse, addiction and overdose a priority. Other work on this important issue is underway within HHS. The evidence-based HHS-wide opioid initiative focuses on three priority areas: informing opioid prescribing practices, increasing the use of naloxone (a rescue medication that can prevent death from overdose) and expanding access to and the use of MAT to treat opioid use disorder.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.