1. Opioid Use Disorder in Pregnancy Tara Benjamin, MD, MS Assistant Clinical Professor Division of Maternal-Fetal Medicine Department of Obstetrics and Gynecology Indiana University School of Medicine

2. Disclosure I have no disclosures

3. Content Learning Objectives Background ~ Epidemiology ~ Complications ~ Terminology Overview of management during pregnancy ~ Rationale ~ Options ~ Recommendations Challenges in clinical care

4. Learning Objectives At the end of this presentation, participants should be better able to… Utilize current terminology regarding Substance Use Disorders. Describe management options for Opioid Use Disorder in pregnancy. Understand the challenges in caring for pregnant women with Opioid Use Disorder.

5. Pre-test The Diagnostic and Statistical Manual of Mental Disorders, 5 th edition, replaced the diagnoses of opioid abuse and opioid dependence with what diagnosis? A.Opioid Dependence Syndrome B.Opioid Addiction C.Opioid Use Disorder D. Opioid Addiction Disorder

6. Pre-Test True or False The severity of Neonatal Abstinence Syndrome is worse in neonates prenatally exposed to Methadone.

7. Pre-test Effective management for pregnant women who abuse opioids includes which of the following: A.Detoxification B.Pharmacotherapy C.Behavioral Therapy D.A and C E.B and C F.All of the above

8. BACKGROUND Epidemiology & Complications

9. EPIDEMIOLOGY ~300,000 ~900,000 www.cdc.gov

10. National Center for Health Statistics

11. COMPLICATIONS MaternalFetal Overdose and death Accidents Hyperalgesia Narcotic Bowel Syndrome Criminal activity Susceptibility to violence With IV use- HIV, Hepatitis, TB, syphilis Placental abruption* Fetal growth restriction* Fetal death* Preterm Labor* Passage of Meconium* Neonatal Neonatal Abstinence Syndrome *Associated with chronic untreated heroin use ACOG Committee Opinion No. 524: Opioid Abuse, Dependence, and Addiction in Pregnancy; 5/2012. Opioid Use Disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis. www.uptodate.com. Retrieved 2/19/2016.www.uptodate.com

12. Neonatal Abstinence Syndrome Hyperactivity of the central & autonomic nervous systems. Uncoordinated sucking reflexes, poor feeding, irritable, high-pitched cry. Methadone-symptoms appear within 72h and last days to weeks. Buprenorphine- symptoms appear within 12-48h, peak at 72-96h, and resolve by 7 days. Severity does not differ based on maternal dosage.

13. NIH National Institute on Drug Abuse COST of NAS

14. 2007 U.S. Societal Costs of Prescription Opioid Abuse Mediation Assisted Treatment Guidelines for Opioid Use Disorders; Michigan Department of Community Health

15. Ultimate Cost

16. Fox59 (March 11, 2016) --Four Indiana health centers received a total of $1.5 million in grant funding for opioid treatment from the U.S. Department of Health and Human Services.

17. BACKGROUND Terminology

18. TERMINOLOGY Bags, Bundles, and Bricks 1 bag of heroin ≅ 33mg $10-25 10 bags = 1 bundle ≅ 330mg $70-80 10 bundles = 1 brick ≅ 1 g $300-500 Note that geographic and dealer variations exist. 5 bundles= 1 brick in Philly. www.heroinhelper.com

19. Terminology Opioids - Natural and synthetic substances - Bind endogenous mu opioid receptors in the nervous system. - Produce analgesic, euphoric, and CNS depressant effects. Opiates - Subclass of opioids derived from compounds of the opium poppy -Morphine, codeine Mu receptor Heroin Converted to morphine

20. Terminology Opioids - Natural and synthetic substances - Bind endogenous mu opioid receptors in the nervous system. - Produce analgesic, euphoric, and CNS depressant effects. Opiates - Subclass of opioids derived from compounds of the opium poppy -Morphine, codeine Mu receptor Heroin GiGi GiGi Converted to morphine

21. Terminology Opioids - Natural and synthetic substances - Bind endogenous mu opioid receptors in the nervous system. - Produce analgesic, euphoric, and CNS depressant effects. Opiates - Subclass of opioids derived from compounds of the opium poppy -Morphine, codeine Mu receptor Heroin GiGi GiGi Converted to morphine Inhibits GABA release

22. Terminology Opioids - Natural and synthetic substances - Bind endogenous mu opioid receptors of the nervous system. - Produce analgesic, euphoric, and CNS depressant effects. Opiates - Subclass of opioids derived from compounds of the opium poppy -Morphine, codeine Mu receptor Heroin GiGi GiGi Converted to morphine Inhibits GABA release Lack of GABA leads to continuous DA activation.

23. Controlled Use Genetic Predisposition Environmental Factors Impulsive Use Mediated by positive reinforcement Neuroadaptation Poor executive functioning Poor inhibitory control Compulsive Use Mediated by negative reinforcement Tolerance & Dependence Reward-Deficit Cycle

24. Terminology Opioid Use Disorder (OUD) Diagnosis that has replaced opiate dependence and opiate addiction in the Diagnostic and Statistical Manual of Mental Disorders-V. CHRONIC, remitting, relapsing condition. 11 diagnostic criteria Severity and acuity specifications.

25. Terminology- Types of Opioids Long-acting Onset of withdrawal is within 24-36h of use. Withdrawal may last several weeks. Examples: Methadone, oxycontin, Fentanyl patch Short-acting Onset of withdrawal is within 4-6h of use. Withdrawal may last up to 72h. Usually subsides by 1 week Examples: Heroin, Tramadol, Morphine, Hydrocodone, Codeine, Oxycodone, Hydromorhpone

26. Mechanism of Action Methadone - Long-acting, synthetic, full opioid agonist that is slowly metabolized and has high fat solubility. Buprenorphine - Short-acting, synthetic, partial opioid agonist with high affinity, low intrinsic activity, and slow dissociation. Naloxone - Synthetic opioid antagonist that blocks opioid receptors, preventing opioid effects. Used to treat overdose.

27. Terminology- Opioid Effect Methadone- full agonist Buprenorphine- partial agonist “ceiling effect” Naloxone- antagonist Opioid Effect Log Dose

28. Overview of Opioid Use Disorder Management in Pregnancy

29. OUD Mngmt PharmacologicBehavioral Detoxification Management Options

30. OUD Mngmt PharmacologicBehavioralDetoxification Management Options Preferred

31. OUD Mngmt in Pregnancy Pharmacologic Buprenorphine Methadone Behavioral Cognitive Behavioral Tx Contingency Mngmt Prenatal Care

32. Rationale for Medication Assisted Therapy in Pregnancy Prevent complications of illicit opioid use and narcotic withdrawal Encourage prenatal care and drug treatment Reduce criminal activity Avoid risks of associating with a drug culture

33. Advantages Buprenorphine Neonates with NAS required 89% less morphine, had a 43% shorter hospital stay, and 58% shorter duration of treatment. Lower risk of overdose. Fewer drug interactions. Outpatient treatment*. Methadone The structure of daily visits is good for some patients. * Providers must have a DEA waiver and comply with FDA regulations to prescribe Buprenorphine.

34. Disadvantages Buprenorphine Risk of hepatic dysfunction. Lack of long-term data on infant and child effects. Clinically important patient dropout rate due to dissatisfaction. Risk of precipitated withdrawal with induction. Risk of diversion. Methadone Requires daily visits to a licensed treatment program. Risk of overdose.

35. Management

36. Other Management Considerations

37. Challenges in Clinical Care

38. Identifying candidates early in pregnancy Paucity of Addiction Medicine Subspecialists and buprenorphine providers in IN. Few providers who will prescribe buprenorphine for pregnant women. Administrative work in obtaining prior authorizations. Difficulty in transitioning to a postpartum provider. Lack of resources for patients requiring advanced levels of care.

39. Post-test The Diagnostic and Statistical Manual of Mental Disorders, 5 th edition, replaced the diagnoses of opioid abuse and opioid dependence with what diagnosis? A.Opioid Dependence Syndrome B.Opioid Addiction C.Opioid Use Disorder D. Opioid Addiction Disorder

40. Post-Test True or False The severity of Neonatal Abstinence Syndrome is worse in neonates prenatally exposed to Methadone.

41. Post-test Effective management for pregnant women who abuse opioids includes which of the following: A.Detoxification B.Pharmacotherapy C.Behavioral Therapy D.A and C E.B and C F.All of the above

42. Take home points New DSM-V terminology = Substance + Use Disorder Opioid Use Disorder is a chronic, relapsing, remitting condition for which effective treatment during pregnancy combines pharmacologic therapy and behavioral therapy. NAS is a treatable condition that is less severe in neonates exposed to Buprenorphine. There are many challenges in caring for pregnant women with OUD.