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Editorial |

The Potential Impact on Children of the CDC Guideline for Prescribing Opioids for Chronic Pain Above All, Do No Harm FREE

Neil L. Schechter, MD1,2; Gary A. Walco, PhD3,4
[+] Author Affiliations
1Department of Anesthesiology, Harvard Medical School, Boston, Massachusetts
2Pain Treatment Service, Department of Anesthesiology, Perioperative, and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
3Departments of Anesthesiology and Pain Medicine, Pediatrics, and Psychiatry, University of Washington School of Medicine, Seattle
4Department of Anesthesiology and Pain Medicine, Seattle Children’s Hospital, Seattle
JAMA Pediatr. 2016;170(5):425-426. doi:10.1001/jamapediatrics.2016.0504.
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Published online

In an effort to address the epidemic of opioid misuse and related deaths from overdose in the United States, the Centers for Disease Control and Prevention (CDC) produced the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain.1 This document is intended to offer “recommendations for prescribing opioids for chronic pain outside of active cancer, palliative, and end-of-life care.”1 The guideline focuses largely on the risks and benefits of opioid treatment and attempts to offer evidence to support their safe, efficacious, and appropriate use.

The current concerns about opioids ensure that this document will receive widespread scrutiny and that there will be extensive discussion regarding the 12 recommendations that are made in the guideline.1 It is a certainty that some will argue that the recommendations unnecessarily restrict opioid use and that individuals will suffer unnecessarily as a result; others may feel that the recommendations are too lenient regarding opioid indications and will promote further opioid abuse and dependence. Most will argue that the evidence supporting the recommendations is inadequate to justify the conclusions that have been reached.

For better or worse, in theory, none of this is germane to the pediatric community because the guideline states in its second paragraph that it is intended to apply to patients 18 years of age or older with chronic pain. Unfortunately, the exclusion of children from the national discussion on pain is not new. The Interagency Pain Research Coordinating Committee on the National Pain Strategy likewise did not consider children in their public draft.2 While there may be some potential secondary benefit to the pediatric population from the guideline if it does, in fact, limit the excess availability of opioids and the potential for inadvertent opioid poisoning in young children and pilfered recreational use by adolescents, clearly children and adolescents would benefit from guidelines tailored to their needs. We are concerned, however, that because this guideline is written for primary care clinicians, family physicians and pediatricians will assume that they can be extrapolated downward to the pediatric population for whom it was not intended.

There are understandable reasons why children are not included in these discussions. The methodological and ethical complexities involved in pediatric pain research have dampened the interest of the research community, and the relatively small market for analgesia that children offer has limited the interest of the pharmaceutical industry in supporting this work. As a result, evidence on which to base clinical decisions is even sparser than that for adults.

Yet, there are compelling reasons why pediatric pain should be a part of any national consensus. Children younger than 18 years of age represent nearly one-quarter of the US population. Between 1994 and 2007, the rate at which opioids are prescribed to adolescents 15 to 19 years of age has doubled,3 and on the CDC website, it states that nearly 2 million Americans 12 years of age or older either abused or were dependent on opioid painkillers in 2013.4 Further data are cited that indicate that 2.6 of 100 000 persons in the United States between the ages of 15 and 24 years died of a prescription opioid overdose.5 In a study of illicit drug use among teens, opioids accounted for 79% of the significant morbidity and 100% of the deaths.6 Certainly, therefore, this is an issue that impacts children.

Despite the importance of the issue, however, as mentioned previously, pain research for children has been limited, at least in part, because it is very different than similar research for adults. There are differences in the physiological, assessment, and psychological factors in children compared with adults that demand the use of different methods to measure efficacy. In addition, the experience of pain and some of the diseases responsible for it are different for children. For example, potent opioid analgesia may be indicated for certain chronic pediatric conditions such as osteogenesis imperfecta, epidermolysis bullosa, and neuromuscular diseases. Although not restricted to children, sickle cell vaso-occlusive episodes represent a condition for which opioid prescribing should be encouraged and for which opioids may be required as long-term treatment. These syndromes all have a clear underlying pathology that includes nociceptive stimulation that may be reduced or eliminated with opioids. This thoughtful perspective on opioid use was recently reinforced by the leadership at the US Food and Drug Administration.7

Approaches that embrace a balance between the problems with opioid prescribing and the treatment of pain in the young are encouraged because data clearly show that poorly treated pain in the young has deleterious long-term consequences on the development of pain systems and related responses, as well as psychological well-being.810 Furthermore, the long-term impact of pain on a developing organism (ie, a child) may be quite different than on an adult and may suggest more aggressive, or at least different, interventions. Recent functional magnetic resonance imaging data demonstrate the impact of chronic pain on the brain and its recovery when the pain dissipates11; one could assume that the effect is amplified in a developing brain. Unfortunately, the impact of long-term opioid use on the immature brain is also unknown. For all of these reasons, it is critical that children are not merely considered “little adults” and that simple extrapolation of adult research be avoided.12

Recognition of the unique attributes of pediatric pain has occurred in some of the recently issued guidelines. For example, in the most recent guideline on opioid prescribing for chronic noncancer pain issued by the State of Washington, a leading state in legislating change in opioid prescribing, a chapter on pediatrics was included,13 even though firm evidence of safety and efficacy is lacking.

The CDC guideline is now published, without regard for pediatric patients. To address the needs of this age group, we recommend a series of short-, medium-, and long-term strategies. Immediately, the CDC is urged to provide an explicit and definitive statement that this guideline should not be applied to those younger than 18 years of age for fear of untoward consequences. Perhaps the title should be changed to reflect this (eg, 2016 CDC Guideline for Prescribing Opioids for Chronic Pain in Adults). In the medium term, as soon as possible, an expert panel should be assembled to combine available evidence and expert opinion in order to delineate specific indications and safety concerns around the use of opioids for chronic pain in infants, children, and adolescents. We recognize the limitations of the available literature, but many of the adult recommendations were made largely on the basis of expert consensus. In the long term, it is imperative to use developmental methods, including cross-sectional, cross-sequential, and longitudinal designs, to better define risk factors and understand the trajectories that predispose one to problems with chronic pain and substance misuse.12 Future guidelines should embrace a life-span developmental approach to these thorny issues so that our entire population can benefit from these important documents.

ARTICLE INFORMATION

Corresponding Author: Gary A. Walco, PhD, Department of Anesthesiology and Pain Medicine, Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105 (gawalco@uw.edu).

Published Online: March 15, 2016. doi:10.1001/jamapediatrics.2016.0504.

Conflict of Interest Disclosures: Dr Walco has provided consultation to Pfizer Pharmaceuticals, Purdue Pharma, and Janssen Pharmaceuticals in the prior 3 years. No other disclosures are reported.

Additional Contributions: We thank Charles Berde, MD, PhD, for his thoughtful review of the manuscript.

REFERENCES

Dowell  D, Haegerich  TM, Chou  R.  CDC guideline for prescribing opioids for chronic pain—United States, 2016 [published online March 15, 2016]. JAMA. doi:10.1001/jama.2016.1464.
Interagency Pain Research Coordinating Committee. National Pain Strategy: a comprehensive population health-level strategy for pain. http://iprcc.nih.gov/docs/drafthhsnationalpainstrategy.pdf. Accessed May 19, 2015.
Fortuna  RJ, Robbins  BW, Caiola  E, Joynt  M, Halterman  JS.  Prescribing of controlled medications to adolescents and young adults in the United States. Pediatrics. 2010;126(6):1108-1116.
PubMed   |  Link to Article
Substance Abuse and Mental Health Services Administration. Results From the 2012 National Survey on Drug Use and Health (NSDUH): Summary of National Findings. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2013. NSDUH Series H-46, US Dept of Health and Human Services Publication SMA13-4795.
Injury prevention & control: prescription drug overdose. Centers for Disease Control and Prevention website. http://www.cdc.gov/drugoverdose/data/overdose.html. Accessed February 8, 2016.
Zosel  A, Bartelson  BB, Bailey  E, Lowenstein  S, Dart  R.  Characterization of adolescent prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-related Surveillance (RADARS(®)) System. J Am Acad Child Adolesc Psychiatry. 2013;52(2):196-204.
PubMed   |  Link to Article
Califf  RM, Woodcock  J, Ostroff  S.  A proactive response to prescription opioid abuse [published online February 4, 2016]. N Engl J Med. doi:10.1056/NEJMsr1601307.
Schechter  NL.  Pediatric pain management and opioids: the baby and the bathwater. JAMA Pediatr. 2014;168(11):987-988.
PubMed   |  Link to Article
Fitzgerald  M.  The development of nociceptive circuits. Nat Rev Neurosci. 2005;6(7):507-520.
PubMed   |  Link to Article
Grunau  RE. Long-term effects of pain in children. In: McGrath  PJ, Stevens  BJ, Walker  SM, Zempsky  WT, eds. Oxford Textbook of Paediatric Pain. Oxford, England: Oxford University Press; 2014:30-38.
Becerra  L, Sava  S, Simons  LE,  et al.  Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome. Neuroimage Clin. 2014;6:347-369.
PubMed   |  Link to Article
Berde  CB, Walco  GA, Krane  EJ,  et al.  Pediatric analgesic clinical trial designs, measures, and extrapolation: report of an FDA scientific workshop. Pediatrics. 2012;129(2):354-364.
PubMed   |  Link to Article
Walco  GA. Managing chronic non-cancer pain in children and adolescents. In: Washington State Agency Medical Directors’ Group, eds. Interagency Guideline on Prescribing Opioids for Pain; 2015:45-47. http://www.agencymeddirectors.wa.gov/Files/2015AMDGOpioidGuideline.pdf. Accessed February 24, 2016.

Figures

Tables

References

Dowell  D, Haegerich  TM, Chou  R.  CDC guideline for prescribing opioids for chronic pain—United States, 2016 [published online March 15, 2016]. JAMA. doi:10.1001/jama.2016.1464.
Interagency Pain Research Coordinating Committee. National Pain Strategy: a comprehensive population health-level strategy for pain. http://iprcc.nih.gov/docs/drafthhsnationalpainstrategy.pdf. Accessed May 19, 2015.
Fortuna  RJ, Robbins  BW, Caiola  E, Joynt  M, Halterman  JS.  Prescribing of controlled medications to adolescents and young adults in the United States. Pediatrics. 2010;126(6):1108-1116.
PubMed   |  Link to Article
Substance Abuse and Mental Health Services Administration. Results From the 2012 National Survey on Drug Use and Health (NSDUH): Summary of National Findings. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2013. NSDUH Series H-46, US Dept of Health and Human Services Publication SMA13-4795.
Injury prevention & control: prescription drug overdose. Centers for Disease Control and Prevention website. http://www.cdc.gov/drugoverdose/data/overdose.html. Accessed February 8, 2016.
Zosel  A, Bartelson  BB, Bailey  E, Lowenstein  S, Dart  R.  Characterization of adolescent prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-related Surveillance (RADARS(®)) System. J Am Acad Child Adolesc Psychiatry. 2013;52(2):196-204.
PubMed   |  Link to Article
Califf  RM, Woodcock  J, Ostroff  S.  A proactive response to prescription opioid abuse [published online February 4, 2016]. N Engl J Med. doi:10.1056/NEJMsr1601307.
Schechter  NL.  Pediatric pain management and opioids: the baby and the bathwater. JAMA Pediatr. 2014;168(11):987-988.
PubMed   |  Link to Article
Fitzgerald  M.  The development of nociceptive circuits. Nat Rev Neurosci. 2005;6(7):507-520.
PubMed   |  Link to Article
Grunau  RE. Long-term effects of pain in children. In: McGrath  PJ, Stevens  BJ, Walker  SM, Zempsky  WT, eds. Oxford Textbook of Paediatric Pain. Oxford, England: Oxford University Press; 2014:30-38.
Becerra  L, Sava  S, Simons  LE,  et al.  Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome. Neuroimage Clin. 2014;6:347-369.
PubMed   |  Link to Article
Berde  CB, Walco  GA, Krane  EJ,  et al.  Pediatric analgesic clinical trial designs, measures, and extrapolation: report of an FDA scientific workshop. Pediatrics. 2012;129(2):354-364.
PubMed   |  Link to Article
Walco  GA. Managing chronic non-cancer pain in children and adolescents. In: Washington State Agency Medical Directors’ Group, eds. Interagency Guideline on Prescribing Opioids for Pain; 2015:45-47. http://www.agencymeddirectors.wa.gov/Files/2015AMDGOpioidGuideline.pdf. Accessed February 24, 2016.

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