Evidence-Based Reviews

Opioid use disorder during pregnancy

Current Psychiatry. 2011 March;10(3):35-46

References

1. Flavin J, Paltrow LM. Punishing pregnant drug-using women: defying law medicine, and common sense. J Addict Dis. 2010;29(2):231-244.

2. American Psychiatric Association. Opioid use disorder. DSM-5 development. Available at: http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=460#. Accessed January 26 2011.

3. Pichini S, Puig C, Zuccaro P, et al. Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the “Meconium Project. “ Forensic Sci Int. 2005;153:59-65.

4. Mitchell JL, Brown G. Physiological effects of cocaine heroin, and methadone. In: Engs RC, ed. Women: alcohol and other drugs. Dubuque, IA: Kendall/Hunt Publishing Co; 1990:53-60.

5. Center for Substance Abuse Treatment. Medication-assisted treatment for opioid addiction during pregnancy. In: Medication-assisted treatment for opioid addiction in opioid treatment programs. Treatment Improvement Protocol (TIP) Series 43. Rockville MD: Substance Abuse and Mental Health Services Administration; 2005, reprinted 2006. DHHS Publication No. (SMA) 06-4212.

6. Helmbrecht GD, Thiagarajah S. Management of addiction disorders in pregnancy. J Addict Med. 2008;2(1):1-16.

7. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.

8. Chasnoff IJ, Wells AM, McGourty RF, et al. Validation of the 4P’s Plus screen for substance use in pregnancy validation of the 4P’s Plus. J Perinatol. 2007;27:744-748.

9. Jones HE. The challenges of screening for substance use in pregnant women: commentary on the 4P’s Plus tool. J Perinatol. 2005;25:365-367.

10. Center for Substance Abuse Treatment. Substance abuse treatment: addressing the specific needs of women. Treatment Improvement Protocol (TIP) Series 51. Rockville MD: Substance Abuse and Mental Health Services Administration; 2009. HHS Publication No. (SMA) 09-4426.

11. Christmas JT, Knisely JS, Dawson KS, et al. Comparison of questionnaire screening and urine toxicology for detection of pregnancy complicated by substance use. Obstet Gynecol. 1992;80:750-754.

12. Wunsch MJ, Weaver MF. Alcohol and other drug use during pregnancy: management of the mother and child. In: Ries RK Fiellin DA, Miller SC, et al, eds. Principles of addiction medicine, 4^th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2009:1111-1124.

13. Ondersma SJ, Winhusen T, Erickson SJ, et al. Motivation enhancement therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy? Drug Alcohol Depend. 2009;101(1-2):74-79.

14. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy: effects and management. Obstet Gynecol Clin North Am. 1998;25:139-151.

15. Comfort M, Zanis DA, Whiteley MJ, et al. Assessing the needs of substance abusing women. Psychometric data on the psychosocial history. J Subst Abuse Treat. 1999;17:79-83.

16. Kissin WB, Svikis DS, Moylan P, et al. Identifying pregnant women at risk for early attrition from substance abuse treatment. J Subst Abuse Treat. 2004;27:31-38.

17. Jones HE, O’Grady KE, Malfi D, et al. Methadone maintenance vs. methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict. 2008;17(5):372-386.

18. Luty J, Nikolaou V, Bearn J. Is opiate detoxification unsafe in pregnancy? J Subst Abuse Treat. 2003;24(4):363-367.

19. Vesga-Lopez O, Blanco C, Keyes K, et al. Psychiatric disorders in pregnant and postpartum women in the United States. Arch Gen Psychiatry. 2008;65(7):805-815.

20. Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008;35(3):245-259.

21. NIDA International Program. National Institute on Drug Abuse. Methadone research web guide. Available at: http://international.drugabuse.gov/collaboration/guide_methadone/index.html. Accessed December 2, 2010.

22. Wittmann BK, Segal S. A comparison of the effects of single- and split-dose methadone administration on the fetus: ultrasound evaluation. Int J Addict. 1991;26:213-218.

23. DePetrillo PB, Rice JM. Methadone dosing and pregnancy: impact on program compliance. Int J Addict. 1995;30:207-217.

24. Jansson LM, Dipietro JA, Velez M, et al. Maternal methadone dosing schedule and fetal neurobehaviour. J Matern Fetal Neonatal Med. 2009;22(1):29-35.

25. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP) Series 40. Rockville MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.

26. Jones HE, Johnson RE, Jasinski DR, et al. Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. Drug Alcohol Depend. 2005;78(1):33-38.

27. Jones HE, Johnson RE, Jasinski DR, et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients; effects on the neonatal abstinence syndrome. Drug Alcohol Depend. 2005;79(1):1-10.

28. Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010;363(24):2320-2331.

29. Nanovskaya T, Deshmukh S, Brooks M, et al. Transplacental transfer and metabolism of buprenorphine. J Pharmacol Exp Ther. 2002;300(1):26-33.

30. Svikis DS, Golden AS, Huggins GR, et al. Cost-effectiveness of treatment for drug-abusing pregnant women. Drug Alcohol Depend. 1997;45:105-113.

31. Jones HE, O’Grady K, Dahne J, et al. Management of acute postpartum pain in patients maintained on methadone or buprenorphine during pregnancy. Am J Drug Alcohol Abuse. 2009;35(3):151-156.

General objectives
Prevent opioid withdrawal signs and symptoms
Provide a comfortable induction onto the medication
Block the euphoric and reinforcing effects of illicit opioids while also attenuating the motivation (craving, social interactions) to use illicit opioids and other drugs
Enhance treatment retention
Create a more optimal environment for behavioral and psychosocial interventions
Pregnancy-specific objectives
Eliminate or reduce fetal exposure to illicit opioids and other illicit drugs
Stabilize the intrauterine environment
Enhance involvement in prenatal care
Create an optimal environment to address pregnancy-specific problems
Source: Reference 20

Delivery and postnatal care

Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.³⁰

During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.³¹ Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.

To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.

CASE CONTINUED: Medication change

Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.

After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.

Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.

Clinical Point

Buprenorphine may have some advantages over methadone during pregnancy but more research is needed

Related Resources

Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.

Drug Brand Names

Clinical Point

During delivery, pain medication should not be withheld solely because a woman has a history of addiction-related disorders

Aripiprazole • Abilify
Buprenorphine and naloxone •Suboxone
Buprenorphine • Subutex
Butorphanol • Stadol
Citalopram • Celexa
Fentanyl • Duragesic, Sublimaze, others
Methadone • Dolophine
Naloxone • Narcan
Naltrexone • ReVia
Nalbuphine • Nubain
Oxycodone • Oxycontin

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.

The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.

Acknowledgments

The authors wish to thank Kathleen Peak for her administrative assistance and Paul Horn, Professor, Department of Mathematical Sciences and Cincinnati VA, for statistical assistance.

Breast-feeding: OK while receiving opioid agonist treatment

Methadone is compatible with breast-feeding^a and the American Academy of Pediatrics^b and World Health Organization^c recommend breast-feeding for women receiving methadone unless there are contraindications such as human immunodeficiency virus infection.^a Instruct mothers to seek medical advice if their breast-fed infant appears sedated.^b Because the amount of methadone in breast milk is very small and depends on the methadone dose, the breast milk of mothers receiving methadone may be insufficient to prevent neonatal abstinence syndrome (NAS) and infants still may require opioid agonist treatment.^d

Although breast-feeding by mothers receiving buprenorphine is not recommended by the drug’s manufacturer, there is consensus that buprenorphine is found in low levels in breast milk^{e, f} and is compatible with breast-feeding.^g Because of partial agonism and low oral bioavailability, buprenorphine may not suppress NAS from methadone withdrawal. Always obtain appropriate informed consent.

References

a. Chasnoff If, Neuman MA, Thornton C, et al. Screening for substance abuse in pregnancy: a practical approach for the primary care physician. Am J Obstet Gynecol. 2001;184(4):752-758.

b. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human breast milk. Pediatrics. 2001;108:776-789.

c. The WHO Working Group, Bennet PN, ed. Monographs on individual drugs (WHO Working Group). In: Drugs and human lactation. Amsterdam, The Netherlands: Elsevier; 1988:319-320.

d. Jansson LM, Velez M, Harrow C. Methadone maintenance and lactation: a review of the literature and current management guidelines. J Hum Lact. 2004;20(1):62-71.

e. Grimm D, Pauly E, Pöschl J, et al. Buprenorphine and norbuprenorphine concentrations in human breast milk samples determined by liquid chromotography-tandem mass spectrometry. Ther Drug Monit. 2005;27(4):526-530.

f. Lindemalm S, Nydert P, Svensson JO, et al. Transfer of buprenorphine into breast milk and calculation of infant drug dose. J Hum Lact. 2009;25(2):199-205.

g. Center for Substance Abuse Treatment. Special populations: pregnant women and neonates. In: Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP)) Series 40. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2004. DHHS Publication No. (SMA) 04-3939.