Opioid Diversion and Abuse: The Effect on Children and What is Being Done

By Raeford (Rae) Brown, MD, FAAP
Professor of Anesthesiology and Pediatrics
University of Kentucky/The Kentucky Children’s Hospital

Opioids are prescribed daily for acute and chronic pain management in patients throughout the world. Appropriate use is usually effective in assisting thoughtful clinicians with managing discomfort in a compassionate fashion. Studies have shown appropriate use of opioids to be safe and effective in adults, adolescents, children, and infants. As pain practitioners, we are all aware that, although for many years, fear of the use of opioids in children reduced the appropriate management of pain in some patients, over the course of the last 25 years, hundreds of studies have demonstrated that experience of pain is common to all patients regardless of their developmental level, that untreated pain can have chronic deleterious implications and that there can sometimes be permanent effects from the lack of treatment. We also realize that opioids are readily available for the treatment of pain and have been used in almost every setting. Opioids are useful, safe when used appropriately, and effective.

Problematic in this picture is a relatively recent change in society that has accelerated the diversion of prescription opioids, leading to a rise in morbidity and mortality. The availability of thousands of units of extended release and long-acting opioids since 1995 may have been instrumental in this change.  Clinicians, dependent on the pharmaceutical industry for education and training about new products, were led to believe that some new agents were pharmacologically superior to older agents and, specifically, would not produce problematic use in patients – read "long-term abuse".  For the patient with long-term low back pain, these drugs were a Godsend, producing pain relief for the first time in many years.  Many of the patients who received these medications used the drugs and predictably saw their dose requirements escalate over time. Most adult patients take the drugs as long as they are being prescribed. When they are no longer being prescribed, or when the doses no longer meet the patient’s physiological need, users will often find “their drug” on the street.  If their drug is not available, users will turn to whatever is most available at the time, often to heroin, which is available in the United States in unbelievable quantities and at a price point below prescription drugs. The use of heroin has risen dramatically in the last ten years.  At this time, the Drug Enforcement Administration, the Food and Drug Administration, and the Center for Disease Control and Prevention have been instructed by the President and the Congress to focus on this as a public health issue of the first order. More opioids on the street seem to invite the abuse of these agents.

As advocates for children, these findings are stark and frightening as they relate to their health and well-being. The impact of this healthcare crisis goes well beyond the simple diversion and abuse of drugs. It undermines the stability of families and the opportunity for a child’s continued social and intellectual development. The importance of this concept cannot be overstated and at this juncture, we appear to be well on our way to creating a generation of lost children.

Though fewer children than adults become addicted to opioids, it is not outside of the realm of the possible. Adolescents with chronic disease or with acute or chronic pain syndromes often have difficulty dealing with the use of opioids; management of these drugs without significant supervision is not possible in patients with an immature nervous system. Failure to appropriately manage opioids can be exacerbated by friends who may press the patient to divert their prescription drugs or by parents who may have problems of their own with substance use or abuse.

Much is being done to reduce diversion of prescription drugs. Many states closely track the prescribing behavior of opioids by clinicians. Those states that have well established systems to track prescribing and dispensing practices have, for the most part, been successful in reducing or attenuating the rapid rise in the diversion and abuse of prescription opioids. The focus on diversion of prescription drugs has not reduced the use of heroin, as there appears to be an inverse relationship between the elimination of prescription medicines and the increase in heroin use.   The DEA has closed hundreds of “pill mills” where prescriptions have been produced for no reasonable medical condition.  The Center for Disease Control has begun to educate clinicians about when opioids can be used safely, offering evidence-based guidelines for reasonable patient management. The most recent statement was published in April of 2016. The CDC has reached out to many professional societies, including the American Academy of Pediatrics, to assist in the creation of educational programs that highlight appropriate prescribing practices.

The Food and Drug Administration has also taken an active role. In the last four years, the pharmaceutical industry has been provided guidance about the development of opioid compounds that are more resistant to abuse. In most of these new formulations, the focus has been to block opioid effect after tampering or to reduce the ability of a user to crush the pill so that it cannot be snorted or injected. The transition by users of ER-LA drugs, from appropriate oral use to snorting or injecting the drug, not only produces immediate and dangerously elevated levels of the drug but is epidemiologically associated with profound respiratory depression or death. Chronic snorting or IV injection of adulterated product, even in narcotic tolerant patients, will produce chronic lung disease often related to pulmonary hypertension.

The FDA has been at the forefront of the development of risk evaluation and mitigation strategies (REMS) as a part of any new drug application (NDA) for an opioid by the pharmaceutical industry. REMS should include “Elements for Assuring Safe Use” which may include:

1. Provider enrollment and training
2. Patient counseling about the risks and benefits of the chronic use of opioids
3. Safety checks during the medication use process (this may include routine or random drug counts and/or drug screens)
4. Restrictions on the conditions of use (this may include opioid use contracts. The FDA recommends these contracts, but they are not required to be in compliance with regulations).
   

The FDA has been relatively prescriptive about the requirements for REMS and it is the drug's sponsor that creates the program. The FDA is involved in the development of these documents before marketing and continues to monitor safety issues associated with the drug after marketing to determine if the REMS has managed to reduce the risk of diversion and abuse.

As this program is relatively new, the creation of risk mitigation strategies and the analysis of follow-up marketing information continue to evolve. The new Commissioner of the FDA, Dr. Robert Califf, has assured the Congress that the FDA will make an increased effort to confirm that the analysis of the outcome of REMS for opioids will be carefully considered and that more resources will be provided to consider all opioid compounds that are presented as new drugs.

REMS is certainly not the magic bullet for solving our opioid diversion problems. Theoretically, monitoring programs such as this should be effective in reducing diversion and thereby take illicit opioids off of the market. However, the assessment of efficacy is deterred by the lack of baseline data about how many opioid units there are and how many patients are currently diverting. Current methods for deriving this information include such nonspecific methods as reviewing poison control data and state-by-state mortality data. This program, however, is a good start as it includes training of clinicians, monitoring of patients, and continuing oversight by the FDA. The intent is that the REMS program will continue to evolve as post-marketing data is obtained and methods of deriving data become more sophisticated.

An outgrowth of the current focus on opioids has been a renewed consideration of the role of the FDA in the management of drugs for infants and children in the United States. To that end, the activity of the Committee on Pediatrics, and the Science Board, both of which report directly to the Commissioner, has increased dramatically. The effect of this activity remains to be seen, but it certainly offers an opportunity for consideration of drugs other than opioids. The NIH can support further funding of projects that evaluate the effect of new and old drugs on children. Supportive statements from the FDA may be critical in affecting that outcome.