Neonatal Abstinence Syndrome Medication

  • Author: Ashraf H Hamdan, MD, MBBCh, MSc, MRCP; Chief Editor: Ted Rosenkrantz, MD   more...
 
Updated: Apr 24, 2012
 

Medication Summary

Medications used in patients with neonatal abstinence syndrome (NAS) should be considered when supportive measures fail to ameliorate the infant's withdrawal. This may be manifested early on as difficulty with feeding, extreme irritability, and poor sleeping. If a scoring system is used, pharmacological treatment is commonly started when the average of 3 scores is 8 or more on the Finnegan scale[22] or 4 or more on the Lipsitz scale.

The optimal treatment for neonatal abstinence syndrome has not been established. This is reflected in the considerable heterogeneity in the pharmacologic treatment of neonatal abstinence syndrome among different institutions. Many pharmacological agents have been used to treat neonatal abstinence syndrome. However, few randomized trials have compared the efficacy of the various pharmacological treatments. For opioid related neonatal abstinence syndrome, morphine and methadone are given as substitutes. Nonmorphine treatments (eg, phenobarbital, chlorpromazine, diazepam, clonidine) provide symptomatic relief.

Agthe et al studied 80 infants exposed in utero to methadone or heroin and subsequently had NAS to determine if oral clonidine, an alpha2-adrenergic receptor agonist, would reduce the duration of opioid detoxification.[31] Each infant received oral diluted tincture of opium (dosage according to standardized algorithm) and either oral clonidine (1 mcg/kg q4h) or placebo. Duration of opioid therapy was measured.

Results showed that the median length of therapy was 27% shorter in the clonidine group (11 d) versus placebo (15 d). Seven infants in the clonidine group required restarting opium after initial discontinuation, versus none in the placebo group, although total length of treatment was significantly less in the clonidine group. Higher opium doses were required by 40% of infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. The addition of clonidine to standard opioid therapy reduced the duration of pharmacotherapy for NAS.

A US survey reported that opioid medications are the most commonly used medications for the treatment of both opioid and polydrug withdrawal.[32] Diluted tincture of opium is recommended by the American Academy of Pediatrics for the treatment of neonatal abstinence syndrome due to opioid withdrawal.[33] Diluted tincture of opium is a 25-fold dilution of deodorized tincture of opium. Deodorized tincture of opium is equivalent to anhydrous morphine 10 mg/mL, whereas diluted tincture of opium is equivalent to anhydrous morphine 0.4 mg/mL. As a tincture, opium contains a high amount of alcohol. Diluted tincture of opium (Paregoric) contains 45% alcohol. The Institute for Safe Medication Practices considers this a high alert medication because of the confusion if abbreviated as DTO because the abbreviation could mean deodorized or diluted tincture of opium.

Many neonatal units use proprietary oral or intravenous morphine solutions, and methadone is also used. A recent study showed chlorpromazine to be efficacious, with no adverse effects in neonates with neonatal abstinence syndrome and shorter treatment time when compared with morphine. A large multicenter trial was recommended by the author to confirm the safety and efficacy of chlorpromazine.[34]

Buprenorphine is the first prescription drug approved under the 2000 US Drug Addiction Treatment Act for office based treatment of addiction to narcotics.[35] Buprenorphine has numerous characteristics that make it an attractive agent in the treatment of neonatal abstinence syndrome. Buprenorphine has a ceiling effect for respiratory depression. It does not have the cardiovascular liability associated with methadone and has an established safety profile in adults. Finally, abuse liability is limited, which makes consideration of outpatient treatment for neonatal abstinence syndrome a possibility for carefully screened caregivers. A pilot study showed that the treatment of neonatal abstinence syndrome with sublingual buprenorphine is feasible, has acceptable safety margin, and may represent a novel treatment.[36]

Currently, many infants are exposed to polydrug abuse. Unfortunately, evidence from randomized studies is insufficient to determine the best management for these patients. In 2 randomized trials, phenobarbital (rather than diazepam or paregoric) was best at controlling symptoms in infants exposed to polydrugs. The results of another study suggested that the combination of phenobarbital with diluted tincture of opium may be more effective than diluted tincture of opium alone because the combination was associated with a shorter hospital stay.[28]

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Antiepileptic agents

Class Summary

These drugs have a long half-life and can be orally administered, allowing for the neonate to be discharged and treated as an outpatient.

Disadvantages include lack of effect on GI symptoms and ineffectiveness in treating seizures secondary to withdrawal. In addition, antiepileptics contain 14-25% alcohol, and larger doses are required to achieve the desired effect.

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Phenobarbital (Luminal)

 

Interferes with transmission of impulses from thalamus to cortex of brain. Used as a sedative. Irritability and insomnia are controlled. Available in PO and IV preparations.

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Opiates

Class Summary

These agents are the mainstay of treatment for opiate withdrawal, either alone or in combination with other medications. These agents are CNS depressants with advantages that include oral administration, mild sedation that improves the effectiveness of sucking, and effectiveness in treating seizures secondary to opiate withdrawal.

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Morphine sulfate (Roxanol, Astramorph PF)

 

PO solutions are available in concentrations of 2 mg/mL, 4 mg/mL, and alcohol-free 20 mg/mL. Administered to neonates as diluted PO solution containing 0.4 mg/mL.

Bioavailability is 20-40% when administered orally. Elimination half-life is approximately 9 h. Recommended that Neonatal Abstinence Scoring System be used to guide treatment management of NAS.

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Methadone

 

Long-acting narcotic analgesic. PO bioavailability is 50%, with peak plasma levels obtained in 2-4 hours. Serum half-life ranges from 16-25 hours in neonates and is prolonged in patients with renal failure. Available as PO solutions in 1-mg/mL and 2-mg/mL concentrations containing 8% alcohol and 10-mg/mL alcohol-free solution.

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Contributor Information and Disclosures
Author

Ashraf H Hamdan, MD, MBBCh, MSc, MRCP  Clinical Associate Professor of Pediatrics, Vanderbilt University Medical Center; Neonatologist, Pediatrix Medical Group of Nashville

Ashraf H Hamdan, MD, MBBCh, MSc, MRCP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Scott S MacGilvray, MD  Clinical Professor, Department of Pediatrics, Division of Neonatology, The Brody School of Medicine at East Carolina University

Scott S MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Brian S Carter, MD, FAAP  Professor of Pediatrics (Neonatology), Vanderbilt University School of Medicine; Director, Neonatal Follow-up Program, Monroe Carell Jr Children's Hospital at Vanderbilt

Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Society for Bioethics and Humanities, American Society of Law, Medicine & Ethics, National Hospice and Palliative Care Organization, Society for Pediatric Research, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Carol L Wagner, MD  Professor of Pediatrics, Medical University of South Carolina

Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD  Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Jaques Belik, MD, and Judy Hawes, RN, MN, to the writing and development of this article.

References

  1. Chana S, Anand K. Can we use methadone for Analgesia in neonates?. Arch Dis Child Fetal Neonatal Ed. 2001;85:79-81. [Medline]. [Full Text].

  2. Franck LS, Vilardi J, Durand D, Powers R. Opioid withdrawal in neonates after continuous infusions of morphine or fentanyl during extracorporeal membrane oxygenation. Am J Crit Care. Sep 1998;7(5):364-9. [Medline].

  3. Substance Abuse and Mental Health Services Administration Office of Applied Studies. 2003 National Survey on Drug Use & Health: Results. US Department of Health and Human Services. Available at http://www.drugabusestatistics.samhsa.gov/NHSDA/2k3NSDUH/2k3results.htm. Accessed December, 2007.

  4. Hytinantti T, Kahila H, Renlund M, Jarvenpaa AL, Halmesmaki E, Kivitie-Kallio S. Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero. Acta Paediatr. Aug 2008;97(8):1040-4. [Medline].

  5. Lim S, Prasad MR, Samuels P, Gardner DK, Cordero L. High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome. Am J Obstet Gynecol. Jan 2009;200(1):70.e1-5. [Medline].

  6. Dryden C, Young D, Hepburn M, Mactier H. Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources. BJOG. Apr 2009;116(5):665-71. [Medline].

  7. Wouldes TA, Woodward LJ. Maternal methadone dose during pregnancy and infant clinical outcome. Neurotoxicol Teratol. Jan 25 2010;[Medline].

  8. BJ Cleary, M Eogan, MP O'Connell, T Fahey, PJ Gallagher, T Clarke, et al. Methadone and Perinatal Outcomes – a Prospective Cohort Study. Addiction. [Medline].

  9. Law KL, Stroud LR, LaGasse LL, et al. Smoking during pregnancy and newborn neurobehavior. Pediatrics. Jun 2003;111(6 Pt 1):1318-23. [Medline]. [Full Text].

  10. Haddad PM, Pal BR, Clarke P, Wieck A, Sridhiran S. Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome?. J Psychopharmacol. Sep 2005;19(5):554-7. [Medline].

  11. Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings. US Department of Health and Human Services; September 2011. [Full Text].

  12. SAMHSA. Substance Use among Women During Pregnancy and Following Childbirth. Rockville, MD: Substance Abuse and Mental Health Services Administration; May 21, 2009. [Full Text].

  13. Cairns PA. Drug misuse: Conception into childhood. Current Paediatrics. December 2001;11(6):475-9.

  14. Prentice S. Substance misuse in pregnancy. Obstetrics, Gynaecology & Reproductive Med. September 2007;17:272-7.

  15. Gyarmathy VA, Giraudon I, Hedrich D, Montanari L, Guarita B, Wiessing L. Drug use and pregnancy - challenges for public health. Euro Surveill. Mar 5 2009;14(9):33-6. [Medline]. [Full Text].

  16. Substance Use During Pregnancy: 2002 and 2003 Update. National survey on drug use and health; June 2, 2005. [Full Text].

  17. Lester BM, ElSohly M, Wright LL, Smeriglio VL, Verter J, Bauer CR. The Maternal Lifestyle Study: drug use by meconium toxicology and maternal self-report. Pediatrics. Feb 2001;107(2):309-17. [Medline].

  18. [Guideline] American Academy of Pediatrics Committee on Substance Abuse. Drug-exposed infants. Pediatr. Aug 1995;96(2 Pt 1):364-7. [Medline].

  19. Doberczak TM, Kandall SR, Wilets I. Neonatal opiate abstinence syndrome in term and preterm infants. J Pediatr. Jun 1991;118(6):933-7. [Medline].

  20. Liu AJ, Jones MP, Murray H, Cook CM, Nanan R. Perinatal risk factors for the neonatal abstinence syndrome in infants born to women on methadone maintenance therapy. Aust N Z J Obstet Gynaecol. Jun 2010;50(3):253-8. [Medline].

  21. [Best Evidence] [Guideline] Hudak ML, Tan RC. Neonatal Drug Withdrawal. Pediatrics. January 2012;129(2):e540-560. [Medline]. [Full Text].

  22. Finnegan LP. Neonatal abstinence syndrome: assessment and pharmacolotherapy. In: Neonatal therapy: An update. New York, NY: Excerpta Medica; 1986:122-46.

  23. Ostrea EM, Ostrea AR, Simpson PM. Mortality within the first 2 years in infants exposed to cocaine, opiate, or cannabinoid during gestation. Pediatrics. Jul 1997;100(1):79-83. [Medline]. [Full Text].

  24. Lester BM, Tronick EZ. History and description of the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Pediatrics. Mar 2004;113(3 Pt 2):634-40. [Medline].

  25. Chasnoff IJ. Prenatal substance exposure: maternal screening and neonatal identification and management. Neoreviews. 2003;4(9):e228-e235.

  26. Gray T, Huestis M. Bioanalytical procedures for monitoring in utero drug exposure. Anal Bioanal Chem. Aug 2007;388(7):1455-65. [Medline].

  27. van Huis M, van Kempen AA, Peelen M, Timmers M, Boer K, Smit BJ. Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy. Pediatr Radiol. Mar 2009;39(3):232-8. [Medline].

  28. Kassima Z, Greenough A. Neonatal abstinence syndrome: Identification and management. Current Paediatrics. June 2006;16:172-5.

  29. Lainwala S, Brown ER, Weinschenk NP, Blackwell MT, Hagadorn JI. A retrospective study of length of hospital stay in infants treated for neonatal abstinence syndrome with methadone versus oral morphine preparations. Adv Neonatal Care. Oct 2005;5(5):265-72. [Medline].

  30. Kraft WK, Gibson E, Dysart K, et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. Sep 2008;122(3):e601-7. [Medline].

  31. [Best Evidence] Agthe AG, Kim GR, Mathias KB, et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics. May 2009;123(5):e849-56. [Medline].

  32. Sarkar S, Donn SM. Management of neonatal abstinence syndrome in neonatal intensive care units: a national survey. J Perinatol. Jan 1 2006;26(1):15-7. [Medline].

  33. [Guideline] American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. [published erratum appears in Pediatrics 1998 Sep;102(3 Pt 1):660]. Pediatrics. Jun 1998;101(6):1079-88. [Medline].

  34. Mazurier E, Cambonie G, Barbotte E, Grare A, Pinzani V, Picaud JC. Comparison of chlorpromazine versus morphine hydrochloride for treatment of neonatal abstinence syndrome. Acta Paediatr. Oct 2008;97(10):1358-61. [Medline].

  35. SAMHSA. The Drug Addiction Treatment Act of 2000 (DATA 2000). DHHS; 2000. [Full Text].

  36. Kraft WK, Gibson E, Dysart K, Damle VS, Larusso JL, Greenspan JS. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. Sep 2008;122(3):e601-7. [Medline].

  37. [Guideline] Jansson LM, Choo R, Velez ML, Harrow C, Schroeder JR, Shakleya DM. Methadone maintenance and breastfeeding in the neonatal period. Pediatrics. Jan 2008;121(1):106-14. [Medline].

  38. [Guideline] AAP. Transfer of drugs and other chemicals into human milk. Pediatrics. Sep 2001;108(3):776-89. [Medline].

  39. Anthony BE, Bryan BL. Neonatal Abstinence Syndrome. NeoReviews. 2009;10(5):e222.

  40. Hale TW. Pharmacology review: drug therapy and breastfeeding: antidepressants, antipsychotics, antimanics, and sedatives. NeoReviews. May 2004;e451 -e456.

  41. Irner TB, Teasdale TW, Nielsen T, Vedal S, Olofsson M. Substance use during pregnancy and postnatal outcomes. J Addict Dis. Jan 2012;31(1):19-28. [Medline].

  42. Gray KA, Day NL, Leech S, Richardson GA. Prenatal marijuana exposure: effect on child depressive symptoms at ten years of age. Neurotoxicol Teratol. May-Jun 2005;27(3):439-48. [Medline].

  43. Goldschmidt L, Day NL, Richardson GA. Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol. May-Jun 2000;22(3):325-36. [Medline].

  44. Maternal Resource Center. Prenatal Substance Exposure. April 2008;Available from: National Abandoned Infants Assistance Resource Center. Accessed 2/20/2010. Available at http://aia.berkeley.edu/media/pdf/2008_perinatal_se.pdf.

  45. Jaudes PK, Ekwo E, Van Voorhis J. Association of drug abuse and child abuse. Child Abuse Negl. Sep 1995;19(9):1065-75. [Medline].

  46. Smith DK, Johnson AB, Pears KC, Fisher PA, DeGarmo DS. Child maltreatment and foster care: unpacking the effects of prenatal and postnatal parental substance use. Child Maltreat. May 2007;12(2):150-60. [Medline].

  47. American Academy of Pediatrics. Pickering LK. The Red Book: 2006 Report of the Committee on Infectious Diseases. 27th. 2006.

  48. [Guideline] American Academy of Pediatrics Committee on Fetus and Newborn. The initiation or withdrawal of treatment for high-risk newborns. Pediatrics. Aug 1995;96(2 Pt 1):362-3. [Medline].

  49. Bahwere P, Haumont D, Delange F. Congenital hypothyroidism and neonatal withdrawal syndrome. Eur J Pediatr. Nov 1996;155(11):937-8. [Medline].

  50. Bauer CR. Perinatal effects of prenatal drug exposure. Neonatal aspects. Clin Perinatol. Mar 1999;26(1):87-106. [Medline].

  51. Boukydis CF, Lester BM. The NICU Network Neurobehavioral Scale. Clinical use with drug exposed infants and their mothers. Clin Perinatol. Mar 1999;26(1):213-30. [Medline].

  52. Buchi KF. The drug-exposed infant in the well-baby nursery. Clin Perinatol. Jun 1998;25(2):335-50. [Medline].

  53. Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr. Mar 1986;108(3):456-9. [Medline].

  54. Connolly WB Jr, Marshall AB. Drug addiction, pregnancy, and childbirth: legal issues for the medical and social services communities. Clin Perinatol. Mar 1991;18(1):147-86. [Medline].

  55. Frank L. Assessment and management of opioid withdrawal in ill neonates. Neonatal Network. 1995;14:39-48. [Medline].

  56. Heier LA, Carpanzano CR, Mast J, Brill PW, Winchester P, Deck MD. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol. Sep-Oct 1991;12(5):951-6. [Medline].

  57. Johnson K, Gerada C, Greenough A. Treatment of neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed. Jan 2003;88(1):F2-5. [Medline].

  58. Kallen B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med. Apr 2004;158(4):312-6. [Medline]. [Full Text].

  59. Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy. Effects and management. Obstet Gynecol Clin North Am. Mar 1998;25(1):139-51. [Medline].

  60. Kandall RS. Improving Treatment for Drug-Exposed Infants Treatment Improvement Protocol (TIP) Series 5. Available at http://ncadi.samhsa.gov/govpubs/bkd110/default.aspx. Accessed February, 14 2010.

  61. Kandall SR. Treatment strategies for drug-exposed neonates. Clin Perinatol. Mar 1999;26(1):231-43. [Medline].

  62. Kuschel C. Managing drug withdrawal in the newborn infant. Semin Fetal Neonatal Med. Apr 2007;12(2):127-33. [Medline].

  63. McKim EM. Caffeine and its effects on pregnancy and the neonate. J Nurse Midwifery. Jul-Aug 1991;36(4):226-31. [Medline].

  64. [Best Evidence] Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA. May 18 2005;293(19):2372-83. [Medline].

  65. Oei J, Lui K. Management of the newborn infant affected by maternal opiates and other drugs of dependency. J Paediatr Child Health. Jan-Feb 2007;43(1-2):9-18. [Medline].

  66. Pierog S, Chandavasu O, Wexler I. Withdrawal symptoms in infants with the fetal alcohol syndrome. J Pediatr. Apr 1977;90(4):630-3. [Medline].

  67. SAMHSA. Special issues during pregnancy. Rockford, MD: DHHS; May 21, 2009. [Full Text].

  68. Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. Feb 5-11 2005;365(9458):482-7. [Medline].

  69. Ter Horst PG, Jansman FG, van Lingen RA, Smit JP, de Jong-van den Berg LT, Brouwers JR. Pharmacological aspects of neonatal antidepressant withdrawal. Obstet Gynecol Surv. Apr 2008;63(4):267-79. [Medline].

  70. Theis JG, Selby P, Ikizler Y, Koren G. Current management of the neonatal abstinence syndrome: a critical analysis of the evidence. Biol Neonate. 1997;71(6):345-56. [Medline].

  71. Umans JG, Szeto HH. Precipitated opiate abstinence in utero. Am J Obstet Gynecol. Feb 15 1985;151(4):441-4. [Medline].

  72. Vance JC, Chant DC, Tudehope DI, et al. Infants born to narcotic dependent mothers: physical growth patterns in the first 12 months of life. J Paediatr Child Health. Dec 1997;33(6):504-8. [Medline].

  73. Wagner CL, Katikaneni LD, Cox TH, Ryan RM. The impact of prenatal drug exposure on the neonate. Obstet Gynecol Clin North Am. Mar 1998;25(1):169-94. [Medline].

  74. Young T E, Mangum B. CNS Drugs. In: Thomson Reuters clinical editorial staff. Neofax: A manual of drugs used in neonatal care. 22nd ed. Montvale, New Jersey: Thomson Reuters healthcare; 2009:187-214.

  75. Zeskind PS, Stephens LE. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics. Feb 2004;113(2):368-75. [Medline].

 
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