Epidemic of Prescription Opiate Abuse and Neonatal Abstinence

Abstract

IN THIS ISSUE OF JAMA, PATRICK ET AL 1 DESCRIBE THE EFfects on newborn infants of the widespread availability of prescription opiate medications. These medications provide superior pain control for cancer and chronic pain, but have been overprescribed, diverted, and sold illegally, creating a new opiate addiction pathway and a public health burden for maternal and child health. Overdose mortality and dependence rates are highest among disadvantaged, young adults in rural areas (eg, Maine and Kentucky). Young women are nearly as likely as men to abuse opiate medications, leading to an increase in opiate-dependent newborns treated for withdrawal syndrome or neonatal abstinence syndrome (NAS). The standard of care for opiate addiction during pregnancy is methadone maintenance and psychiatric care. Patrick et al demonstrate that the increase in NAS (from an incidence of 1.20 [95% CI, 1.04-1.37] per 1000 hospital births per year in 2000 to 3.39 [95% CI, 3.12-3.67] per 1000 hospital births per year in 2009) has created a health care encumbrance primarily for state Medicaid budgets. In affected states, methadone treatment programs have expanded rapidly and voluntary prescription monitoring programs identify opiate medication use patterns (ie, opiate prescriptions are tracked and individuals who are “shopping” for physicians to prescribe opiates can be identified). However, the burden of addiction on state Medicaid budgets threatens retrenchment of recently established programs despite increased need. This poses a crisis of care for affected fetuses and newborns. However, without accessible treatment of both maternal opiate addiction and new methods of treating NAS, state and federal systems may pay in the future because many of these infants require special services for developmental and behavioral disorders. Patrick et al also observed that over the last decade, there has been no improvement in NAS treatment efficiency as measured by length of stay (LOS). Furthermore, health care expenditures for NAS have increased during the same period. Even within the context of the status quo of medically managed prenatal methadone treatment, opiate-exposed infants risk adverse effects besides the specter of protracted withdrawal. In their analyses of hospital complications of infants with NAS, Patrick et al confirmed other data demonstrating increased rates of prematurity, respiratory disease, and seizures. Opiate withdrawal is often compounded by comorbid polydrug exposure and maternal psychiatric medications, such as antidepressants and benzodiazepines, which have their own withdrawal syndromes. Although the withdrawal from these agents is milder than opiates, such combinatorial withdrawal complicates neonatal care and often extends LOS. Neonatal abstinence syndrome withdrawal severity affects adaptation to postnatal life in critical regulatory areas of sleep, feeding, and autonomic function. Although 60% to 80% of infants exposed in utero to opiates develop NAS and require prolonged hospitalization, averaging 16 days in the study by Patrick et al, there is still considerable uncertainty regarding optimal detoxification protocols and criteria for opiate withdrawal status typically based on symptoms assessed by the Finnegan score calculated every few hours from birth to day 5. Hospitals and clinicians burdened by the increase in NAS incidence can expend substantial efforts to develop treatment protocols to decrease LOS. As outlined by Patrick et al, most clinicians use oral opiate medication (eg, methadone or morphine) and, in difficult cases, a second-line nonopiate drug with -aminobutyric acid (eg, phenobarbital), benzodiazepine (eg, clonazapam), or anti-adrenergic (eg, clonidine) action. Novel pharmacotherapy research is needed to improve maternal opiate maintenance strategies to protect the fetus from in utero withdrawal, and to reduce the incidence and severity of NAS. These efforts have been frustrated by lack of controlled clinical trials. Methadone maintenance therapy during pregnancy is currently idiosyncratic (eg, lack of standardization in maternal care related todosing)andbasedonmaternalwithdrawal symptoms as gestation progresses. Research aimed at predicting which newborns are most at risk for a difficult withdrawal, or will require prompt treatment, has yielded few leads. In the adult pain management literature, individual genetic differences have been found to predict opiate response and dose