1. Opioid Dependence During Pregnancy Michelle Lofwall, M.D. University of Kentucky 1 © AMSP 2009

2. Challenging to Treat MDs have inadequate training MDs have inadequate training Medical & legal system prejudices Medical & legal system prejudices State reporting requirements State reporting requirements Doctor-patient alliance problems Doctor-patient alliance problems 2 © AMSP 2009

3. What You Need to Know Punishment ≠ effective deterrent Punishment ≠ effective deterrent Comprehensive treatment works! Comprehensive treatment works! 3x  in mom’s opiate use 3x  in mom’s opiate use  Prenatal care  Prenatal care 3x  low birth weight (LBW: <2500 grams) 3x  low birth weight (LBW: <2500 grams)  Perinatal HIV transmission to <2%  Perinatal HIV transmission to <2% 2x  maternal custody in 1 st yr 2x  maternal custody in 1 st yr 3 © AMSP 2009

4. This Lecture Reviews Definitions Definitions Causes, course, prevalence & comorbidity Causes, course, prevalence & comorbidity Medical complications Medical complications Treatment Treatment 4 © AMSP 2009

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6. Abuse ≥ 1 of: Abuse ≥ 1 of: Obligations Obligations Hazardous use Hazardous use Legal Legal Interpersonal problems Interpersonal problems Dependence ≥ 3 of: Dependence ≥ 3 of: Tolerance Tolerance Withdrawal Withdrawal  Amounts or more time  Amounts or more time Desire or unable cut down Desire or unable cut down  Time get, use, or recover  Time get, use, or recover Non-drug activities  Non-drug activities  Physical/psychological problems Physical/psychological problems Abuse & Dependence 6 © AMSP 2009

7. Occurs with  / use OR opioid antagonist Occurs with  /no opioid use OR opioid antagonist ≥ 3 of: ≥ 3 of: Dysphoria (unhappy) Dysphoria (unhappy) Nausea or vomit Nausea or vomit Muscle aches Muscle aches Lacrimation (watery eyes) or rhinorrhea (runny nose) Lacrimation (watery eyes) or rhinorrhea (runny nose) Diarrhea Diarrhea Opioid Withdrawal Yawning Yawning Fever Fever Insomnia Insomnia Mydriasis (big pupils), Mydriasis (big pupils), piloerection (goose bumps), or sweating 7 © AMSP 2009

8. This Lecture Reviews Definitions ✓ Definitions ✓ Causes, course, prevalence & comorbidity Causes, course, prevalence & comorbidity Medical complications Medical complications Treatment Treatment 8 © AMSP 2009

9. Etiology 50% Genes 50% Environment  Availability  Peer use  Drug-using partners  Hx victimization 9 © AMSP 2009

10. Chronic Relapsing Course >50% relapse >50% relapse >90% use opioids before pregnancy >90% use opioids before pregnancy 20x  mortality vs. Ø substance disorder dx 20x  mortality vs. Ø substance disorder dx 10 © AMSP 2009

11. Prevalence of Opiate Use Opiate % Opiate + 11 © AMSP 2009

12. >10% Axis I LBW with mood disorder Other Drugs & Psych Dxs 12 © AMSP 2009 > 90% Cigs LBW Premature SIDS Stillbirths >10% Cocaine Placental abruption Premature

13. Complex Social Problems >50% single moms & unemployed >50% single moms & unemployed >25% hx of physical/sexual abuse >25% hx of physical/sexual abuse Low socioeconomic status Low socioeconomic status Adversely affects pregnancy Adversely affects pregnancy  Prenatal care  Prenatal care  Direct harm  Direct harm 13 © AMSP 2009

14. Risky Behaviors Sharing needles, unprotected sex, dealing Sharing needles, unprotected sex, dealing Mom’s infections  risk of: Mom’s infections  risk of: Premature contractions & labor Premature contractions & labor Breakdown fetal membranes & abortion Breakdown fetal membranes & abortion Difficult to separate out opioid effects Difficult to separate out opioid effects 14 © AMSP 2009

15. This Lecture Reviews Definitions ✓ Definitions ✓ Causes, course, prevalence & comorbidities ✓ Causes, course, prevalence & comorbidities ✓ Medical complications Medical complications Treatment Treatment 15 © AMSP 2009

16. Maternal & Fetal Problems Multifactorial etiology Multifactorial etiology HIV: 25% transmit HIV: 25% transmit Hep C: ~5% transmit Hep C: ~5% transmit Endocarditis  heart failure  hypoxia Endocarditis  heart failure  hypoxia Nutritional deficiency – e.g., 25% Fe-defic Nutritional deficiency – e.g., 25% Fe-defic 16 © AMSP 2009

17. Fetal Hypoxia Unstable fetal environment 17 © AMSP 2009

18. Newborn Birth Outcomes ~50% LBW (~20% with rx) ~50% LBW (~20% with rx) Death Death ~25% HIV (<2% with rx) ~25% HIV (<2% with rx) Meconium aspiration (stool inhaled into lungs) Meconium aspiration (stool inhaled into lungs) ~10% Microcephaly (small head) ~10% Microcephaly (small head) 18 © AMSP 2009

19. Neonatal Abstinence Syndrome (NAS) 19 © AMSP 2009

20. NAS Definition Central nervous system excitability Central nervous system excitability Autonomic nervous system  Autonomic nervous system  GI system malfunction GI system malfunction Respiratory distress Respiratory distress 20 © AMSP 2009

21. NAS Time course depends on: Time course depends on: Opioid half-life (T ½) Opioid half-life (T ½) Fetal opioid storage & metabolism Fetal opioid storage & metabolism Risk factors: Risk factors: Opioid dependent mom  70% chance NAS Opioid dependent mom  70% chance NAS Smoking  severity Smoking  severity Prematurity  severity Prematurity  severity 21 © AMSP 2009

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23. This Lecture Reviews Definitions ✓ Definitions ✓ Causes, course, prevalence & comorbidities ✓ Causes, course, prevalence & comorbidities ✓ Medical complications ✓ Medical complications ✓ Treatment Treatment 23 © AMSP 2009

24. 4 Treatments Reviewed Psychosocial rx without medication Psychosocial rx without medication Methadone maintenance (MM) Methadone maintenance (MM) Methadone-assisted withdrawal Methadone-assisted withdrawal Buprenorphine (Subutex®) maintenance Buprenorphine (Subutex®) maintenance 24 © AMSP 2009

25. Psychosocial Interventions Cornerstone Cornerstone Therapeutic alliance Therapeutic alliance Expect demanding & resistant behavior Expect demanding & resistant behavior Complete assessment Complete assessment Assist with all problems Assist with all problems 25 © AMSP 2009

26. Methadone Maintenance Long T ½ (27 hrs), synthetic opioid agonist Long T ½ (27 hrs), synthetic opioid agonist Strict federal regulations Strict federal regulations Opioid dependent > 1 yr (unless preg) Opioid dependent > 1 yr (unless preg) > 18 yrs unless parental consent/failed rx > 18 yrs unless parental consent/failed rx Daily visits x 90 days Daily visits x 90 days 26 © AMSP 2009

27. Many Treatment Goals Mother: Mother:  /stop withdrawal  /stop withdrawal  /stop drug use  /stop drug use Prenatal/med/psych rx Prenatal/med/psych rx Psychosocial probs Psychosocial probs Supportive network Supportive network Parenting skills Parenting skills 27 © AMSP 2009

28. Many Treatment Goals Fetus/neonate Fetus/neonate Stable intrauterine environment Stable intrauterine environment Stop intox/withdrawal cycles Stop intox/withdrawal cycles Deliver term/healthy newborn Deliver term/healthy newborn + maternal/fetal bond + maternal/fetal bond 28 © AMSP 2009

29. Components of MM Treatment Multidisciplinary team Multidisciplinary team Individual & group counseling Individual & group counseling Parenting classes Parenting classes Daily oral methadone dosing Daily oral methadone dosing Start at 30 mg (40 mg max day 1) Start at 30 mg (40 mg max day 1) > 50 mg maintenance dose > 50 mg maintenance dose Blocks + illicit opioid effects Blocks + illicit opioid effects Prevents withdrawal Prevents withdrawal 29 © AMSP 2009

30. MM Benefits 3x  in mom’s opiate use 3x  in mom’s opiate use  Prenatal care  Prenatal care 3x  LBW 3x  LBW  Perinatal HIV transmission to <2%  Perinatal HIV transmission to <2% 2x  maternal custody of newborn 2x  maternal custody of newborn 30 © AMSP 2009

31. MM Limitations Availability Availability Limited patient acceptance Limited patient acceptance Does not  incidence of NAS Does not  incidence of NAS Report of fine motor skill problems Report of fine motor skill problems 31 © AMSP 2009

32. Methadone-assisted Withdrawal 1970’s = standard rx until fetal deaths 1970’s = standard rx until fetal deaths Utilized if MM not available or accepted Utilized if MM not available or accepted Goals: Goals:  Mother/fetus opioid withdrawal  Mother/fetus opioid withdrawal Achieve opioid free state in mom/fetus Achieve opioid free state in mom/fetus Deliver term, healthy fetus with no NAS Deliver term, healthy fetus with no NAS 32 © AMSP 2009

33. Components of Withdrawal Treatment Inpatient Inpatient OB monitors fetus daily for distress OB monitors fetus daily for distress Stabilize on methadone then taper dose Stabilize on methadone then taper dose If fetal distress – slow taper,  dose If fetal distress – slow taper,  dose 3 & 7 day tapers at specialty units 3 & 7 day tapers at specialty units Discharge Discharge Con’t outpatient rx to maintain abstinence Con’t outpatient rx to maintain abstinence 33 © AMSP 2009

34. Withdrawal Outcomes >50% relapse >50% relapse Problem > opioid withdrawal Problem > opioid withdrawal Problem = medical & psychosocial Problem = medical & psychosocial Compared to MM, detox alone results in: Compared to MM, detox alone results in: 2x  + urine drug test at delivery 2x  + urine drug test at delivery 5x  days in trt 5x  days in trt 6 fewer OB appts 6 fewer OB appts No diff in NAS or birth outcomes No diff in NAS or birth outcomes 34 © AMSP 2009

35. Buprenorphine Maintenance 2002 approved rx for non-preg opioid depend 2002 approved rx for non-preg opioid depend Partial opioid agonist Partial opioid agonist Enhanced safety profile Enhanced safety profile T ½ = 37 hrs T ½ = 37 hrs Office-based Office-based 35 © AMSP 2009

36. Buprenorphine Maintenance Must become qualified to prescribe Must become qualified to prescribe Potential advantages Potential advantages Similar outcomes as MM Similar outcomes as MM Large on-going clinical trial Large on-going clinical trial 36 © AMSP 2009

37. This Lecture Reviewed Definitions ✓ Definitions ✓ Causes, course, prevalence & comorbidities ✓ Causes, course, prevalence & comorbidities ✓ Medical complications ✓ Medical complications ✓ Treatment ✓ Treatment ✓ 37 © AMSP 2009