A comprehensive review article in Obstetrics and Gynecology summarizes troubling data on the epidemic of opioid use disorder (OUD) during pregnancy, and the subsequent sharp rise in the incidence of neonatal abstinence syndrome (NAS) (withdrawal symptoms in newborns). The article also evaluates recent policy decisions and discusses their implications.
Opioid treatment programs (OTPs) have a key stake in the policy proceedings. OTPs need to be aware that the massive increase in the incidence of OUD and NAS will almost certainly continue, so they need to be prepared. They also need to follow the changes in protocols. Policymakers’ decisions will have important implications for women who become pregnant during OTP treatment, and for pregnant women with an untreated OUD who are referred to an OTP.
Some recent health policy and legislative initiatives spurred by the opioid epidemic have benefited patients; others have harmed them; some have even involved criminal penalties.
Evaluating Health Policy
Treating OUD. Treatment options for OUD are medication-assisted treatment (MAT) with methadone or buprenorphine. Detoxification or withdrawal during pregnancy carries many disadvantages for mother and child, and the American College of Obstetrics and Gynecology (ACOG) and other major medical organizations do not recommend it.
In 20 states, according to a 2014 HHS publication on Medicaid coverage, Medicaid 2013 preferred drug lists did not include methadone—a distinct disadvantage to OTPs—yet Medicaid covers buprenorphine in all 50 states. The authors refer to this lack of Medicaid methadone coverage as “a missed opportunity to provide comprehensive drug treatment services for pregnant women.” They point to the HHS publication, which estimates that methadone yields $37.72 in benefits for every $1 in cost.
Some states impose restrictions on Medicaid eligibility and benefits, such as requiring prior authorization and limiting quantity and lifetime treatment.
Protecting Mothers and Infants
The report discusses several legislative plans, the most important being “Prenatal Drug Use and Newborn Health” (The Protecting Our Infants Act of 2015).
This major legislation, released as a document in February 2015, identifies program gaps and directs the Department of Health and Human Services (DHHS) to take several specific actions. DHHS was also to report back to Congress with evidence-based recommendations one year after the bill became law. The Protecting Our Infants Act was passed with broad bipartisan support; President Obama signed it into law November 25, 2015.
As for funding, Congress must allocate money before action can be taken. But comments from lawmakers prior to the signing suggest that funding will happen; a way will be found.
A Call to Arms
The article calls for medical societies to coordinate their professional guidelines and advise policymakers. It also calls for health care providers to act as gatekeepers, screening all pregnant patients for OUD, and helping, where appropriate, with referral and enrollment in medication-assisted treatment programs.
Will Physicians Become Simply Gatekeepers?
When recommendations and guidelines are in place, can physicians still choose the best treatments for their patients?
The Ohio Story: Doctors’ Ethical Dilemma
A situation in Ohio in 2011, reported in PLOS, raises concern.
Ohio state law obligated physicians performing a medication abortion—a nonsurgical procedure in which medications are taken to induce an abortion—to follow an obsolete protocol. The result: medication doses that were too high, causing “significant increases in medical interventions, side effects, and costs.”
PLOS noted that “laws like Ohio’s prohibit clinicians from practicing medicine based on the latest developments in clinical research . . . This law will continue to require physicians to provide care that may fall below the accepted standard of care, placing them in an ethical dilemma.”
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002110.
Anti-choice issues were underlying the state’s actions, but this example clearly illustrates the power of state government to force physicians to use a protocol. This particular protocol happened to be obsolete. The situation would have been much worse if the protocol had been dangerous.
AT Forum contacted ACOG for their comments about the potential negative impact on patients when policy conflicts with medical evidence. “There should not be political interference with patient care and we have had success at the federal level working together with Congress and peer organizations to pass positive legislation that frames the issue of opioid use during pregnancy in the public health, as opposed to punitive, space,” said ACOG Vice President Hal C. Lawrence, MD. “However, the states are much more varied in their approach and some pass laws or set precedents penalizing pregnant women with OUDs.
“This is a challenge that we will continue to face, and physicians and others will need to continue to advocate at the state and federal levels to defend evidence-based approaches to treating OUD in pregnancy, and NAS,” Dr. Lawrence said.
Protocols and Product Labeling
What about protocols containing specific dosages? Some time ago, John McCarthy, MD, ABAM, who will chair a panel at the upcoming meeting of the American Association for the Treatment of Opioid Dependence (AATOD), developed a high-dose, split-dose methadone protocol for pregnant women. The protocol is still used in the California clinic he headed until recently. In a recent study, only 29% of newborns on his protocol required treatment of NAS, vs. published rates of 60% to 80% with other methadone dosages.
AT Forum asked Dr. McCarthy, “If an FDA protocol is published, will you and others no longer be able to use your protocol?”
“Our divided-dose protocol is not yet standard,” he said, “although the science supporting divided doses is very strong. Nor is our individualized dose range—20 mg/day to 415 mg/day—something that would go well with those who think less methadone is better, no matter how severe the mother’s withdrawal symptoms.” He added that it is hard to see a protocol actually going against pharmacokinetic science and restricting what physicians can do.
FDA Regulatory Powers
For clarification on regulatory issues, protocols, and the role of the U.S. Food and Drug Administration (FDA), AT Forum contacted Mark L. Hudak, MD, chairman of the department of pediatrics at Wolfson Children’s Hospital, University of Florida College of Medicine—Jacksonville.
As a former member of the American Academy of Pediatrics (AAP) Committee on Drugs, Dr. Hudak co-authored the clinical guideline, Neonatal Drug Withdrawal, the committee’s landmark 2012 report.
http://pediatrics.aappublications.org/content/129/2/e540.long
What we learned from Dr. Hudak was reassuring. The FDA labels for both methadone and buprenorphine include an indication for maintenance treatment of opioid dependence or addiction. The labels provide additional information about the potential effects of these drugs on the fetus, including the risk of NAS, but do not prohibit their use in pregnant women.
Dr. Hudak noted that the FDA has no authority to interfere with the doctor’s decision, with respect to treating the mother—and no intention of doing so. Congress has granted FDA regulatory authority over drug manufacturing and approval, but not over physician prescription of approved drugs to individual patients.
FDA Labeling and NAS
“In regard to babies experiencing opioid withdrawal, none of the medications we commonly use—morphine, methadone, buprenorphine, or phenobarbital—received label indications from the FDA to treat babies with NAS,” Dr. Hudak said.
In fact, he noted that the FDA label for methadone specifically states that “neonatal opioid withdrawal syndrome . . . should be treated according to protocols developed by neonatology experts.”
Lack of a Protocol Can Mean Changes in Treatment
When Dr. Hudak helped draft the clinical guidance document for NAS, many physicians did not follow a common protocol, so there was a wide variation in treatment within each hospital. Most physicians would use an opioid as a first-line treatment, but approaches differed on when to start treatment, what drug and dose to use initially, and how to escalate treatment and wean the baby. So when another physician took over the baby’s care, the treatment approach often changed.
A Protocol Can Offer Several Treatment Pathways
The AAP guideline recommended that each hospital treating babies with NAS adopt a common protocol.
“A protocol could offer several pathways, depending on a standardized evaluation and the baby’s response to treatment,” said Dr. Hudak. He explained that many more centers have now standardized their approach, and length of treatment and hospital stays are shorter.
“Protocols differ from one hospital to another, and clinical studies have not defined an optimal protocol, so it’s easy to see why no government body could have regulatory authority and tell physicians what drug to use in what patients at what time.”
Dr. Hudak recommended a protocol for everyone in his unit. “It offered several pathways, depending on evaluation and the baby’s response to treatment. The good news is that many more centers now standardize their approach.”
Another advantage: “With such a wide range of acceptable practices, it’s easy to see why no government body could have regulatory authority and tell physicians what drug to use, in what patients, at what time,” he said.
The Next Steps
Regarding OTP patients: under the code of federal regulations (42 CFR 8.12), OTPs must maintain current policies and procedures that reflect the special needs of pregnant patients. “Prenatal care and other gender-specific services . . . must be provided either by the OTP or by referral to appropriate healthcare providers.”
OTP patients will be included in new evidence-based recommendations. According to Dr. McCarthy, data from current studies indicate that these recommendations should include monitoring patients’ methadone dose throughout pregnancy, not just the third trimester.
Recommendations should also include dosage increases. “The pre-pregnancy dose of methadone is never effective,” Dr. McCarthy believes. To claim that it is pretends that metabolic changes do not occur. They do; usually the rate of metabolism rises progressively, and the methadone dose needs to be increased accordingly.”
Outlook: Mixed, but Hopeful
The rise in the incidence of OUD and NAS continues. But with Congress likely to fund The Protecting Our Infants Act, setting in motion a host of actions, specific evidence-based treatment and management recommendations for OUD and NAS should soon emerge.
Protocols will be revised. The country’s OTPs and hospitals will put the new OUD protocols into practice. Patients who are pregnant will ultimately benefit—as will those patients’ unborn babies—and there is hope for new protocols to help newborns with NAS as well.
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References
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Substance Abuse and Mental Health Services Administration. Federal Guidelines for Opioid Treatment Programs. HHS Publication No. (SMA) PEP15-FEDGUIDEOTP. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2015.
Upadhyay UD, Johns NE, Combellick SL, Kohn JE, Keder LM, Roberts SCM. Comparison of outcomes before and after Ohio’s law mandating use of the FDA-approved protocol for medication abortion: A retrospective cohort study. PLOS. August 30, 2016. http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002110.
White House Office of National Drug Control Policy. Epidemic: responding to America’s prescription drug abuse crisis. https://www.whitehouse.gov/sites/default/files/ondcp/policyand-research/rx_abuse_plan.pdf.
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