Opioid Withdrawal in Pregnancy

Opioids/Opiates

As most people are aware, opioids have gotten a lot of attention recently due to their addictive potential and harmful outcomes in overdose. It’s true that opioids are a dangerous medication, but that doesn’t mean they don’t have a place in patient care. The stigma that has surfaced surrounding the discussion of opioids has created a barrier to discussing important questions: when are opioids okay to use in pregnancy? How much is too much? How can I stop taking them safely? Is this going to be harmful to my baby?

Chronic pain is a condition that affects up to 1 in 5 adults in the United States1. Treatment of pain, particularly chronic pain, is difficult to do well. Physicians are responsible for weighing the risks and benefits of writing prescriptions for pain medications, while also putting trust in patients to use them appropriately.  Opioids are a good option for treatment of pain, as they decrease pain signals sent in the brain, creating an analgesic (pain relieving) effect. However, when treating pain in the long-term, particularly during pregnancy, they can be a dangerous option.

Under the umbrella term “narcotics” we include both opiates and opioids. Opiates are naturally occurring alkaloid compounds found in opium, including morphine, codeine, and thebaine. Opioids are synthetic/semisynthetic compounds, including heroin, hydrocodone (Vicodin), oxycodone (OxyContin), buprenorphine, methadone, and fentanyl (Campbell, 2016). Though usually prescribed for pain, these drugs can also be used for cough and diarrhea. In addition to decreasing pain, they can create a feeling of euphoria, which leads to potential misuse and addiction. Over time, the body will develop a tolerance to the drug (requiring increasing doses to achieve the same effect) as well as a physiologic dependence (needing the drug in order to avoid the adverse symptoms of withdrawal). Of primary concern is the risk of overdose, decreased respiratory drive, and death. Since respiratory tolerance does not occur as quickly as analgesic tolerance, tolerant users are still at increased risk of respiratory depression at increased doses2.  

Withdrawal

In a person physiologically dependent on opioids, stopping the drug abruptly will lead to withdrawal. Typical symptoms of withdrawal include pain, nausea, diarrhea, runny nose, watery eyes, sweating, tremor, and goose bumps (hence the term cold turkey, used to describe abrupt cessation of opioids causing chills and skin that looks like that of a turkey). Withdrawal can last anywhere from a few days to several weeks, depending on the drug. Although it does put significant stress on the body, opioid withdrawal in adults is not life threatening in and of itself.

Neonatal Opioid Withdrawal Syndrome

In mothers taking opioids during pregnancy, the medications are able to cross the placenta and enter the baby. Use during pregnancy carries the risk of preterm delivery, poor fetal growth, and possible birth defects3. Upon delivery, the concerns shift to neonatal withdrawal, since the baby is no longer receiving the opioids it was during the mother’s pregnancy. Symptoms of neonatal withdrawal include irritability, tremor, high-pitched cry, sweating, sneezing, hyperthermia, poor feeding, diarrhea, and increased respiratory rate- a syndrome we call neonatal abstinence syndrome or neonatal opioid withdrawal syndrome. Most concerning is the fact that this could lead to seizures in babies. As of now, there is not evidence suggesting that there are long-term effects of neonatal abstinence syndrome4.

Detoxification During Pregnancy

Due to the risks associated with neonatal withdrawal, it is preferred that a pregnant mother discontinues opioid use prior to delivery of her baby. However, this is a solution that is easier said than done. Withdrawal is stressful on the body- both for mother and baby. It is hard to say with current studies whether or not it can be dangerous for a woman to go through detox while pregnant. Two commonly cited reports from the 1970s did raise concern for harmful effects to the baby5,6, such as increased signs of stress and risk of stillbirth, though more recent studies haven’t found clear evidence that this is true7,8. One review including 1,097 pregnancies found that “no increased fetal risks due to tapering or detoxification from opioid drugs were identified”9. This review included both mothers who went through detoxification with medication-assisted therapy and those who went through detox without medications. One weakness here is that it is difficult to quantify harm to the baby, and more studies are needed to definitively say it is or is not harmful in the long-term to undergo detoxification during pregnancy.

Medication-assisted withdrawal

One option for detoxification from opioid use is to use medications, namely buprenorphine or methadone, to assist in the process. Buprenorphine works by binding to the same receptor in the brain as opioids, but with different strength, therefore alleviating withdrawal symptoms without creating a “high”. Methadone also binds to this receptor, but with the same strength and a longer duration, thereby creating a tapering effect that can decrease the high and improve the transition off other medications. Each may be a reasonable option both in pregnancy and otherwise.

At this point, the American College of Obstetricians and Gynecologists states that medication-assisted treatment, such as treatment with methadone or buprenorphine, is preferred over acutely withdrawing without medications. This is largely due to the greater risk of relapse in withdrawal without medications. One review of three studies, involving a total of 235 women, concluded that there was an increased risk of relapse with detoxification treatment compared to opioid replacement therapy, but that detoxification did not alter the risk of preterm birth or neonatal abstinence syndrome10.

The choice between methadone and buprenorphine is one that must be made on an individualized basis. Some benefits to buprenorphine compared to methadone include easier access, lower risk of overdose, fewer drug interactions, and possibly a decreased risk of preterm birth, low birth weight, and neonatal withdrawal11. However, some down sides to buprenorphine are that you must have already gone through detoxification to initiate the drug (or it will precipitate withdrawal), relapse rates are higher, and long-term data is not yet available. Additionally, since methadone is long-acting, if the baby withdraws from methadone at birth he/she may have a lengthy stay in the neonatal intensive care unit (possibly a couple of weeks). All in all, undergoing detoxification, with or without the assistance of medications, is one that should be supervised by a doctor and individualized to the patient.

Potential regimens

Buprenorphine11: Due to the way that buprenorphine partially binds to opioid receptors, therapy can be started only after discontinuation of other opioids, once symptoms of withdrawal have begun. After this, you will likely be given a film or tablet to place under your tongue. The dose will be closely monitored for the first few days, and increased until you no longer have bothersome symptoms of withdrawal. Once you are stable on a particular dose, the length of treatment is up to you and your doctor. Many people choose to remain on buprenorphine for years to come, though the choice to slowly taper off the medication is also an option.

Methadone11: Methadone therapy should begin as early as possible in the pregnancy. It is not necessary to already be in withdrawal when you start methadone; however, as methadone is a long-acting opioid, withdrawal symptoms will likely begin to appear 4-6 hours after your last dose of short-acting opioids. Withdrawal symptoms are likely to last 1-3 days, though the severity and duration of these symptoms will vary depending on the type and amount of opioid that was being taken. Like buprenorphine, the dose of methadone will be slowly increased until withdrawal symptoms subside. Methadone prescribing is monitored closely, so as a patient you will likely be going to a “methadone clinic” quite often in addition to regular urine drug screens- as much as about once a week. How long you stay on methadone is again up to you and your doctor, but this is a long-term treatment that will likely take place over the upcoming months to years, with a minimum of one year being recommended12.

Taper without medications: Tapering off opioids without assistance from medications remains an option; however, it should be done relatively slowly. There isn’t a consensus about exactly what that looks like, but the CDC recommendation is to decrease the dose by about 10% per week for someone who has been taking opioids for weeks to months, or even as little as 10% per month in someone who has been taking them longer13. Depending on the dosage of opioids, then, this process can again take weeks to months.

 

Conclusions:

  • It can be quite dangerous to withdraw from opioids without medical assistance. Going through withdrawal during pregnancy can be stressful to both mother and baby, but remaining on opioids can mean that the baby can withdraw at birth. Negative effects of withdrawal in a mother can be minimized with medications and slow tapering regimens.
  • The American College of Obstetricians and Gynecologists (ACOG) recommends medication assisted therapy for opioid use disorder in pregnancy (i.e., buprenorphine or methadone taper), as outcomes are superior to withdrawal without medications (i.e., “cold turkey”).
  • The choice to use buprenorphine vs. methadone is one that must be made on a person-to-person basis depending on personal preference and access to care.

 

Hannah Wilkerson, MS3

Thomas W. Hale, R.Ph., Ph.d.

Teresa Baker, MD

 

1) Dahlhamer J, Lucas J, Zelaya, C, et al. Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults — United States, 2016. MMWR Morb Mortal Wkly Rep. 2018. DOI: 10.15585/mmwr.mm6736a2

2) Emily O. Dumas and Gary M. Pollack. Opioid Tolerance Development: A Pharmacokinetic/Pharmacodynamic Perspective. The AAPS Journal, Vol. 10, No. 4. 2008. DOI: 10.1208/s12248-008-9056-1

3) Basics About Opioid Use During Pregnancy. Centers for Disease Control and Prevention. 2019. https://www.cdc.gov/pregnancy/opioids/basics.html
4) Steve N. Caritis MD, Ashok Panigrahy MD. Opioids affect the fetal brain: reframing the detoxification debate. American Journal of Obstetrics and Gynecology. 2016. DOI: 10.1016/j.ajog.2019.07.022

5) Frederick P. Zuspan MD, Janis A. Gumpel MD, Alfonso Mejia-Zelaya MD, John Madden MD, Roy Davis D.Mn. Fetal stress from methadone withdrawal. American Journal of Obstetrics and Gynecology. 1975. DOI: 10.1016/0002-9378(75)90613-4

6) José Luis Rementería MD, Nemesio N. Nunag MD. Narcotic withdrawal in pregnancy: Stillbirth incidence with a case report. American Journal of Obstetrics and Gynecology. 1973. DOI: 10.1016/0002-9378(73)90953-8

7) Jennifer Bell MD, Craig V. Towers MD, Mark D. Hennessy MD, Callie Heitzman RN, Barbara Smith, Katie Chattin. Detoxification from opiate drugs during pregnancy. American Journal of Obstetrics and Gynecology. 2016. DOI: 10.1016/j.ajog.2016.03.015

8) Jason Luty, Ph.D., MRCPsycha, Vasilis Nikolaou, B.Sc., M.Sc.b, Jenny Bearn, MRCP, MRCPsych. Is opiate detoxification unsafe in pregnancy? Journal of Substance Abuse Treatment. 2003.

9) Craig V. Towers, MD, FACOG, Paul Terry, PhD, Breanne Rackley, Mark Hennessy, MD, Kevin Visconti, MD. Fetal Outcomes with Detoxification from Opioid Drugs during Pregnancy: A Systematic Review. American Journal of Perinatology. 2019. DOI: 10.1055/s-0039-1688908

10) Michelle J. Wang, Spencer G. Kuper, Brian Sims, Cayce S. Paddock, John Dantzler, Suzanne Muir, Lorie M. Harper . Opioid Detoxification in Pregnancy: Systematic Review and Meta-Analysis of Perinatal Outcomes. American Journal of Perinatology. 2019. DOI: 10.1055/s-0038-1670680

11) Neil S Seligman, MD, Brian J Cleary, PhD, Vincenzo Berghella, MD. Methadone and buprenorphine pharmacotherapy of opioid use disorder during pregnancy. UpToDate. 2018

12) National Institute of Drug Abuse. Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition). 2018.

13) Centers for Disease Control and Prevention. CDC Guideline for Prescribing Opioids for Chronic Pain. 2019.

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