Treating Pregnant and Parenting Women for Substance Use Disorders: Behavioral and Medication Strategies



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50 years of documented benefits of methadone during pregnancy

  • 50 years of documented benefits of methadone during pregnancy
  • Induction is relatively simple
  • Adequate doses are needed to prevent withdrawal and other opioid use
  • Indicators of fetal well-being are less compromised with split-dosing
  • Individualized post-partum dose reviews are needed
  • Breastfeeding is compatible with methadone
  • Methadone: Summary

Buprenorphine

  • A derivative of the opioid alkaloid thebaine
  • Schedule III opioid
  • μ-opioid receptor partial agonist
  • primarily antagonistic actions on κ-opioid and δ-opioid receptors
  • Half-life estimated to fall in the range of 24-60 hours

Buprenorphine mono product

  • Buprenorphine mono product
  • Buprenorphine + naloxone
  • 2 mg and 8 mg sublingual tablets
  • 2 mg/0.5 mg and 8 mg/2 mg sublingual film strips
  • Reviews in Jones et al., Drugs, 2012, and Addiction, 2012

Patient must already be in withdrawal or buprenorphine may precipitate withdrawal.

  • Patient must already be in withdrawal or buprenorphine may precipitate withdrawal.
  • Patients dependent on short-acting opioids (e.g., heroin, most prescription narcotics) will not take as long to enter withdrawal as patients dependent on long-acting opioids (e.g., methadone).
  • Induction typically then takes place over a 3-day period, beginning with either 2 mg or 4 mg, with a maximum dose of:
    • 8 mg – 12 mg on Day 1
    • 12 mg – 16 mg on Day 2
    • 16 mg up to 32 mg on Day 3
  • Buprenorphine: Starting and Dosing

  • Since 1995, over 40 published reports of prenatal exposure to buprenorphine maintenance.
  • Approximately 750 babies prenatally exposed to buprenorphine (number of cases per report ranged from 1 to 159; Median=14).
  • Dose range 0.4 to 32 mg
  • 88% reported concomitant drug use
  • Buprenorphine and Pregnancy
  • Reviews in Jones et al., Drugs, 2012, and Addiction, 2012

Research with buprenorphine not as extensive as with methadone.

  • Research with buprenorphine not as extensive as with methadone.
  • Well-tolerated and generally safe.
  • In contrast to the research with methadone, little research has compared buprenorphine to an untreated control group.
  • Rather, buprenorphine has been compared in both retrospective and prospective studies to methadone.
  • Majority of research would suggest that maternal outcomes are not in any way different than for methadone.
  • Buprenorphine: Maternal Outcomes
  • Reviews in Jones et al., Drugs, 2012, and Addiction, 2012
  • p = .095
  • p < .01
  • Salisbury et al., Addiction, 2012

Incidence rate for NAS is estimated to be 50% – about the same as for methadone

  • Incidence rate for NAS is estimated to be 50% – about the same as for methadone
  • NAS onset approximately 48 hours
  • Peaking within approximately 72-96 hours
  • Exceptions to this onset history have been the few neonates with NAS onset of 8-10 days postnatal age
    • such a protracted withdrawal syndrome may to be due to withdrawal from concomitant drug exposure (e.g., benzodiazepines) rather than a direct effect of buprenorphine withdrawal
  • Correlation between buprenorphine dose and NAS severity has been inconsistent
  • Time of first dose of NAS treatment medication has been shown to be later with buprenorphine than methadone ( 71 hours vs 34 hours, respectively)
  • Buprenorphine: NAS
  • Reviews in Jones et al., Drugs, 2012, and Addiction, 2012; Gaalema et al., Drug Alc Depend, 2013
  • Medications that are full agonist opioids can effectively treat pain in patients stabilized on either methadone or buprenorphine.
  • These results are consistent with data from non-pregnant surgery patients.
  • The importance of uninterrupted methadone or buprenorphine treatment in these patients is critical. 
  • Each patient needs a pain management plan before delivery.
  • Buprenorphine: Pain Management
  • Objectives:
  • the need for medication dose adjustments in participants stabilized on buprenorphine or methadone 3 weeks before and 4 weeks after delivery
  • the need for methadone dose adjustments during the first 7 days in participants transferred from buprenorphine to methadone at 5 weeks postpartum
  • Participants: Received a stable dose of methadone (N = 10) or buprenorphine (N = 8) before and 4 weeks after delivery. Buprenorphine-maintained participants were transferred to methadone at 5 weeks postpartum.
  • There were no significant differences pre-delivery and/or post-delivery between the buprenorphine and methadone conditions in the mean ratings of dose adequacy, "liking," "hooked," and "craving" of heroin or cocaine.
  • Patient response to the conversion from buprenorphine to methadone seems variable. Buprenorphine-maintained participants required dose changes postpartum only after they transferred to methadone. Regardless of type of medication, postpartum patients should be monitored for signs of overmedication.
  • Buprenorphine: Postpartum Dosing
  • Jones et al., J Addict Med, 2008
  • Buprenorphine is found in breast milk 2 hours post-maternal dosing
  • Concentration of buprenorphine in breast milk is low
  • Amount of buprenorphine or norbuprenorphine the infant receives via breast milk is only 1%
  • Most recent guidelines: “the amounts of buprenorphine in human milk are small and unlikely to have negative effects on the developing infant”
  • “The advantages of breast feeding prevail despite the risks of an infant opiate intoxication caused by methadone or buprenorphine.”
  • Akinson et al., 1990; Marquet et al., 1997; Johnson, et al., 2001; Grimm et al., 2005; Lindemalm et al., 2009; Jansson et al., 2009; Müller et al., 2011; Reece-Stremtan, Marinelli and The Academy of Breastfeeding Medicine. Breastfeeding Medicine, 2015.
  • Buprenorphine: Breastfeeding
  • Image Credit: “Mother Is Breast Feeding For Her Baby” by Jomphong
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