Treatment of Opioid Use Disorder in Women During Pregnancy and Postpartum

Transcription

1 Treatment of Opioid Use Disorder in Women During Pregnancy and Postpartum Leena Mittal, MD Instructor of Psychiatry, Harvard Medical School Director, Reproductive Psychiatry Consultation Service, Divisions of Women s Mental Health and Medical Psychiatry, Brigham and Women s Hospital Associate Medical Director, MCPAP for Moms *Images used for educational purposes only. All copyrights belong to image owners*

2 Outline Sex-Based/Gender Differences How Pregnancy is Different Pharmacological Approaches to Treatment Postpartum Considerations

3 I was good for 51 years Ms. C is a 52-year-old woman, divorced 1.5 years ago, who was admitted to the medical hospital for treatment of pancreatitis: Treated for alcohol withdrawal at the beginning of admission Alcohol use escalated after divorce Lost her job as a dental hygienist and is nearly losing her home Declined referral for treatment

4 Outline Sex-Based/Gender Differences How Pregnancy is Different Pharmacological Approaches to Treatment Postpartum Considerations

5 Percent Dependent or Abusing in Past Year NSDUH 2013 Sex-Based Differences in SUD (1) Aged 12 or Older Aged 12 to 17 Aged 18 or Older

6 Sex-Based Differences in SUD (2) Women with SUD have a different course/natural history Telescoping accelerated progression from initiation of use to onset of diagnosis of dependence and initiation of treatment seen with ETOH, opioids, cannabis Interpersonal factors modulate progression (partners and children) Greenfield 2010; Greenfield 2016

7 Sex-Based Differences in SUD (3) Biological Menstrual cycle, pregnancy, aging and menopause Ovarian sex steroids impact effects of cocaine, amphetamines, cannabis Sex-based ETOH thresholds Greenfield 2010

8 Sex-Based Differences in SUD (4) Psychiatric comorbidity Mood disorders Eating Disorders PTSD Greenfield 2010

9 Substance Use in Women Women-targeted treatment Women only Mixed gender setting with services (e.g., childcare, prenatal care, integrated HIV care) Women-only treatment associated with lower rates of relapse and improved outcomes in some studies A minority of programs offer womentargeted treatment Greenfield Psychiatr Clin North Am June ; 33(2):

10 Outline Sex-Based/Gender Differences How Pregnancy is Different Pharmacological Approaches to Treatment Postpartum Considerations

11 I just can t get it together (1) Christy, a 32-year-old female, presented to labor and delivery reporting abdominal pain and was around 7 months pregnant

12 I just can t get it together. (2) One prenatal visit - smelled of alcohol Outreach calls from midwife found patient to have slurred speech Intimate partner violence, unstable housing, loss of custody, poor access to food and health care Drinking daily Accepted referral for substance treatment, but did not show for appt

13 What Makes Pregnancy Different? (1) Risks affect both woman and her fetus and eventually her child(ren) -> Dyadic view NOT mother vs baby Physiological changes affect treatment Collaboration with family, child protective services, obstetric providers NIDA (2012). Principles of Drug Addiction Treatment: A Research-Based Guide Winklbaur et al., 2008 Jones, 2010

14 What Makes Pregnancy Different? (2) Postpartum period is a higher risk time for relapse/ decompensation and there is a new baby! Providers may have different feelings about these patients NIDA (2012). Principles of Drug Addiction Treatment: A Research-Based Guide Winklbaur et al., 2008 Jones, 2010

15 Risk of untreated symptoms Risk of treatment

16 Substance Use During Pregnancy Carries Risk for a Woman and Her Fetus - Exposure to teratogens - Limited access to prenatal care - Poor nutrition - Placental insufficiency - Difficulties with labor management - Withdrawal - Infectious risk (e.g., HIV, HBV, HCV) - Overdose Keegan J et al. J Addictive Diseases (2)

17 % using in past month Substance Use in the Past Month, Females ( ) Nonpregnant Pregnant NSDUH 2012

18 Substance Use During Pregnancy Pregnancy is a motivator for cessation Persistence of substance use during pregnancy may represent a particularly refractory and high-risk subpopulation Higher levels of use prior to pregnancy correlate with continued use during pregnancy Most women return to prepregnancy rates of smoking and alcohol use within 6-12 months postpartum Havens JR et al. Drug and Alcohol Dependence 99 (2009) 89 95; NSDUH 2010; Harrison et al Matern Child Health J (2009) 13:

19 Common Presentations Late presentation to prenatal care Acute intoxication Positive toxicologic screen in mother or baby Intrauterine growth restriction detected during antepartum testing Withdrawal suspected in the neonate

20 Remember Our Patient, Christy? Christy, a 32-year-old female, presented to labor and delivery reporting abdominal pain and was around 7 months pregnant

21 One prenatal visit - smelled of alcohol Outreach calls from midwife found patient to have slurred speech Intimate partner violence, unstable housing, loss of custody, poor access to food and health care Drinking daily Accepted referral for substance treatment, but did not show for appt

22 Challenges to the Delivery of Prenatal Care Stigma and shame Refractory illness Providers own emotional reactions Legal issues Access to suitable SUD treatment programs Time elapsed before recognition of pregnancy

23 Toxicologic Screening Maternal screening Prenatal and at the time of delivery Universal screen not recommended Role of negative tests Neonatal screening Serum/urine reflect recent use Hair/meconium reflects use since 2 nd trimester Cord blood Consent Ostrea 2001

24 Reporting to Social Services Laws vary regionally Report on behalf of the child after delivery Psychiatric evaluation is only a PART of the assessment Encourage staff to document parenting knowledge, feeding awareness, care behaviors Allow the mother to demonstrate her capacity SAMHSA CSAT TIP Series, No. 5

25 Opioid Use Disorders in Pregnancy (1) Opioids are not likely directly teratogenic 1,2 Opioid dependence during pregnancy is associated with: Intrauterine growth restriction Intrauterine fetal demise and stillbirth Preterm labor Placental abruption Postpartum hemorrhage Reduced cognitive function in exposed children 1. Kaltenbach et al. Obstetrics and Gynecology Clinics. 1998; 25: Jick et al JAMA. 1981; 246: 343-6

26 Opioid Use Disorders in Pregnancy (2) Risks related to peaks/troughs and intermittent withdrawal Lifestyle factors associated with use/relapse 1. Kaltenbach et al. Obstetrics and Gynecology Clinics. 1998; 25: Jick et al JAMA. 1981; 246: 343-6

27 Opioid Dependence in Pregnancy 90% of female opioid users in the US are of childbearing age 5.63 in 1000 births (0.56%) delivering mothers defined as dependent on or using opioids antenatally High costs associated with maternal and neonatal care Neonatal abstinence syndrome Integrated SUD/prenatal care is effective Finnegan 1986, Patrick 2012; Mittal 2015; Goler 2008

28 Outline Sex-Based/Gender Differences How Pregnancy is Different Pharmacological Approaches to Treatment Postpartum Considerations

29 OUD in Pregnancy is Treated Pharmacologically No FDA-approved treatment Mainstays of treatment: Methadone Buprenorphine (single or combination) Withdrawal MAY present a risk to the fetus 1-5 Risk of stillbirth, intrauterine fetal demise, preterm labor, meconium High risk of relapse after discontinuation of opioids 6 1. Rementeria et al. AJOG. 1973; 2. Zuspan AJOG.. 3. Fricker Arch of Pedi & Adol Med Luty J of Sub Abuse Treat Towers et al AJOG Jones et al. The American Journal on Addictions. 2008

30 Pharmacological Treatment (1) Methadone was long considered standard of care Benefits Drawbacks Buprenorphine is as effective as methadone Collaboration and coordination is essential between providers Fischer 2006, Saia 2016, Park 2012

31 Pharmacological Treatment (2) Opioid agonist/partial agonists are treatment of choice Risks of opioid withdrawal Greatest risk in 1 st and 3 rd trimester In the 2 nd trimester consider VERY gradual detox Absence of prescribing provider Patient preference Detox -> greater risk of relapse in general population and perinatal women Lund 2012, Saia 2016

32 Benefits of Medication in Pregnancy Maternal Benefits 70% reduction in overdose-related deaths Decrease in risk of HIV, HBV, HCV Increased engagement in prenatal care and recovery treatment Fetal Benefits Reduces fluctuations in maternal opioid levels; reducing fetal stress Decrease in intrauterine fetal demise Decrease in intrauterine growth restriction Decrease in preterm delivery Park 2012

33 Neonatal Abstinence Syndrome Related to Opioids (1) Epidemiology Affects approx 47-57% of infants exposed to methadone or buprenorphine 3.39 per 1000 births in the US Wiles 2014; Patrick 2012, Patrick 2015, Fajemirokun-Odudeyi, O. et al. 2006

34 Neonatal Abstinence Syndrome Related to Opioids (2) Costs: - Average LOS 16 days - $720 million in 2009 Less severe in women stabilized on MAT than women using heroin Wiles 2014; Patrick 2012, Patrick 2015, Fajemirokun-Odudeyi, O. et al. 2006

35 Methadone Maternal Considerations (1) MMT during pregnancy associated with: - Improved OB care - Increased fetal growth - Decreased risk of HIV - Decreased risk of preeclampsia - Longer treatment retention - Fewer relapses Saia 2016

36 Methadone Maternal Considerations (2) Monitor for: - Breakthrough withdrawal symptoms in the third trimesters Physiological changes of pregnancy Split dosing - QTc prolongation - Sedation Park 2012, Bogen 2013, Pariente 2016

37 Methadone Fetal Considerations - Decreased heart rate and heart rate variability Greater at peak than trough - Slower breathing movements on BPP - Decreased fetal movements on BPP Salisbury 2012, Zedler 2016

38 Buprenorphine in Pregnancy (1) Buprenorphine is a high-affinity partial agonist at the mu-opioid receptor Buprenorphine has lower OD risk, fewer drug interactions, office-based administration, less risk of sedation than methadone In pregnant patients, buprenorphine and methadone maintenance cause similar reduction in illicit drug use/relapse risk Jones 2010, Blandthorn 2011, Park 2012

39 Buprenorphine in Pregnancy (2) Use buprenorphine alone (not combined with naloxone) (Subutex) theoretical risk of inducing maternal/fetal withdrawal animal data re: teratogenicity Jones 2010, Blandthorn 2011, Park 2012

40 Trends in Buprenorphine Prescriptions Greene P. Outpatient Drug Utilization Trends for Buprenorphine Years

41 Buprenorphine Prescriptions by Sex (2009) Greene P. Outpatient Drug Utilization Trends for Buprenorphine Years

42 Neonatal Abstinence Syndrome After Methadone or Buprenorphine Exposure Jones et al., 2010 Randomized trial of methadone versus buprenorphine during pregnancy Primary outcome: NAS Result: Buprenorphine more effective than methadone

43 Buprenorphine vs Methadone in Pregnancy No apparent difference between buprenorphine and methadone for: - Maternal weight gain - Cesarean section - Abnormal presentation - Use of analgesia - Positive drug screen - Medical complications at delivery Jones 2012

44 Buprenorphine Fetal Effects In analyses of MOTHER participants, buprenorphineexposed fetuses had: - Less motor suppression - Lower incidence of nonreactive nonstress tests - Clinical significance of these findings not clear Salisbury 2012, Zedler 2016

45 Treatment with Buprenorphine During Pregnancy (1) Induction phase Initiation of treatment requires mild withdrawal symptoms Role for fetal monitoring Inpatient vs outpatient Concheiro 2011

46 Treatment with Buprenorphine During Pregnancy (2) Maintenance phase Dose adjustments as pregnancy advances Planning for delivery and postpartum (pain management and relapse prevention) Concheiro 2011

47 Peripartum Pain Management Maintenance doses of methadone or buprenorphine are not sufficient analgesia Patients on agonist treatment report elevated pain scores and have higher medication requirements Nonnarcotic methods Regional (epidural or spinal anesthesia) NSAIDs Avoid high-affinity partial agonists (e.g., nalbuphine) Alford 2006, Meye 2010, Park 2012

48 Naloxone Opioid overdose is a leading cause of death in the US Administration will induce opioid withdrawal Risk of maternal death outweighs fetal risks in the case of overdose All patients with OUD should be offered naloxone Clark 2014; Shepanek 1995

49 Naltrexone Limited human data Animal data suggests not teratogenic Induction onto naltrexone in pregnancy is not recommended For those already using extended release naltrexone/implantable naltrexone, maybe reasonable to continue during pregnancy Saia 2016

50 How Do I Choose? Methadone and buprenorphine are both effective options In a patient stable on treatment, no need to switch In a patient new to treatment, or who wishes to switch, consider: Patient preference Access Need for structured treatment Methadone ->buprenorphine is difficult and not recommended

51 Outline Sex-Based/Gender Differences How Pregnancy is Different Pharmacological Approaches to Treatment Postpartum Considerations

52 NAS Presentation SIGNS Neurologic excitability Tremor, seizure, inc muscle tone, yawning, sneezing, irritability GI dysfunction Feeding diff, vomiting, diarrhea, poor weight gain Autonomic signs Diaphoresis, fever/temp instability IDENTIFICATION OF RISK Maternal history Onset depends on which agent/confounding agents Not dose dependent Tox screens Genetics/ethnic variations Validated scales Finnegan, Lipsitz, NICU Network Neurobehavioral Scale All are subjective Kocherlakota 2014; Wachman et al 2015

53 Treatment of NAS Nonpharmacologic support is firstline Breastfeeding, swaddling, low stimulation environment, non-nutritive sucking Morphine Methadone Buprenorphine Adjunctive Medications Phenobarbital, clonidine Wiles 2014

54 Maternal Dose and NAS Severity Most data suggest no correlation between maternal opioid maintenance therapy dose and the duration or severity of NAS Withdrawal should be treated through pregnancy with dose increases as needed Tobacco and SSRI use may worsen NAS Cleary et al. 2010; Isemann et al. 2010; Jones et al. 2010; Seligman et al

55 NAS and Developmental Outcomes Difficult to determine outcomes given challenges of evaluating pure effects of opioids Some differences in motor outcomes have been seen in the first year of life, though differences disappear over time No pattern of long-term developmental consequences has emerged with opioid exposure Logan 2013, Behnke 2013

56 Buprenorphine - Lactation Reports range from % of maternal weight-adjusted dose present in breastmilk Poor oral bioavailability further limits exposure Unlikely to affect NAS incidence or severity Lindemalm 2009; Ilett 2012, Gower 2015

57 Medication and Lactation (1) In the absence of HIV or ongoing substance use, mothers on methadone and buprenorphine should be encouraged to consider breastfeeding Amount of methadone in breastmilk is low 1-6% of weight-adjusted maternal dose Amount of buprenorphine in breastmilk is low 1-20% of maternal weight-adjusted dose present in breastmilk Poor oral bioavailability further limits exposure Pritham UA et al. J Obstet Gynecol Neonatal Nurs ; Welle-Strand GK et al. Acta Paediatr ; Wachman EM et al. JAMA ; Abdel-Latif ME et al. Pediatrics

58 Medication and Lactation (2) Can observe for neonatal sedation Enhance maternal infant bonding Reinforce maternal role Improve NAS outcomes Pritham UA et al. J Obstet Gynecol Neonatal Nurs ; Welle-Strand GK et al. Acta Paediatr ; Wachman EM et al. JAMA ; Abdel-Latif ME et al. Pediatrics

59 Benefits of Breastfeeding for Newborns with NAS 30% decrease the development of NAS 50% decrease in neonatal hospital stay Improved mother-infant bonding Positive reinforcement for maternal recovery Pritham UA et al. J Obstet Gynecol Neonatal Nurs Welle-Strand GK et al. Acta Paediatr Wachman EM et al. JAMA Abdel-Latif ME et al. Pediatrics

60 Final Case (1) Patient presents to labor and delivery triage area in pain, stating she is in her 9 th month of pregnancy and thinks she may be in labor Patient has healed track marks scars and smells strongly of cigarettes

61 Final Case (2) Her prenatal care records are obtained and reveal she had a history of heroin use earlier in pregnancy, but worked with the practice social worker to move to a residential treatment program and started buprenorphine at 18 weeks GA

62 Case Discussion 1. How do we manage her pain for labor and postpartum? 2. What additional interventions should be recommended? 3. What comorbidity should be considered? 4. What postpartum planning needs to happen?

63 Summary Women with SUD have biological and social differences, especially in pregnancy Pregnancy is a time of opportunity to treat SUD Buprenorphine and methadone are mainstays of treatment during pregnancy Neonatal abstinence syndrome is more prevalent, and an important public health issue Women on buprenorphine and methadone should be encouraged to breastfeed when able

64 Unit References & Resources SAMHSA - Results from the 2013 National Survey on Drug Use and Health (NSDUH): Summary of National Findings Principles of Drug Addiction Treatment: A Research- Based Guide (Third Edition) SAMHSA - Results from the 2013 National Survey on Drug Use and Health (NSDUH): Summary of National Findings SAMHSA - TIP 5: Improving Treatment for Drug- Exposed Infants

65 Additional Recommended Resources PCSS-MAT - Medical/Special Populations PCSS-MAT - Opioid Dependence in Pregnancy: Clinical Challenges PCSS-MAT - Opioid Agonist Treatment During Pregnancy: Is it Time to Revisit Tapering or Detoxification?