Pregnancy, MAT and Addiction

Transcription

1 Pregnancy, MAT and Addiction Carl Christensen, MD, PhD, D-FASAM Clinical Associate Professor, OB Gyn & Psychiatry Wayne State University School of Medicine William Morrone, DO, MPH, DABAM Covenant Hospital OB consultant 1

2 Author credit Today I will present slides from my friend and teacher: Carl CHRISTENSEN, MD, PhD Carl and I have been doing Pregnancy / Addiction for 10 years. We share often and I give him 100% credit. 2

3 Educational Objectives At the conclusion of this activity participants should be able to: Understand the current neurobiological basis for addictive disorders. Be familiar with the three current FDA approved medications for Opioid Use Disorders Be aware of the current recommendations for treatment of Opioid Use Disorder during Pregnancy Review the use of short acting naloxone for reversal of opioid overdose. 3

4 WHY TALK ABOUT THIS? Addiction and Pregnancy 4 4

5 WHY TALK ABOUT THIS? Addiction and Pregnancy 5 5

6 WHY TALK ABOUTTHIS? N.A.S. in Southeastern Mich Addiction and Pregnancy 6 6

7 What is Addiction? Physiology of Addiction 7 7

8 The Nucleus Accumbens: Craving and Reward Physiology of Addiction 8 8

9 VTA: the gas tank : supplies dopamine to the Nucleus Accumbens Physiology of Addiction 9 9

10 Frontal Cortex: Impulse Control Physiology of Addiction 10 10

11 What is Addiction? Addiction is not a problem of drug WITHDRAWAL

12 What is Addiction? It is a problem of: o CRAVING o LOSS OF CONTROL o COMPULSIVE USE o USE DESPITE CONSEQUENCES 12 12

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17 Frontal Cortex and Addiction High flow Healthy Control Cocaine-dependent Gottschalk, 2001, Am J Psychiatry Physiology of Addiction 17 Low flow 17

18 Frontal Cortex and Addiction Non users High blood flow Cocaine users, 10 days sober Cocaine Users, 100 days sober Low blood flow Physiology of Addiction 18 18

19 Frontal Cortex and Addiction Non users High blood flow Cocaine users, 10 days sober Cocaine Users, 100 days sober Low blood flow Physiology of Addiction 19 19

20 Frontal Cortex and Addiction Non users High blood flow Cocaine users, 10 days sober Cocaine Users, 100 days sober Physiology of Addiction 20 Low blood flow 20

21 CONTROL [C-11]d-threo-methylphenidate How Long to recover from Methamphetamine? Normal Control Methamphetamine Abuser (1 month abstinent) high low Volkow et al., J. Neuroscience, Methamphetamine Abuser (14 months abstinent) 21

22 [C-11]d-threo-methylphenidate 30 days abstinent Normal Control high Methamphetamine Abuser (1 month abstinent) low Volkow et al., J. Neuroscience, Methamphetamine Abuser (14 months abstinent) 22

23 [C-11]d-threo-methylphenidate 14 months + to recover from Methamphetamine!!! Normal Control Methamphetamine Abuser (1 month abstinent) high low Volkow et al., J. Neuroscience, Methamphetamine Abuser (14 months abstinent) 23

24 Treatment of Opioid Use Disorder Medication Assisted Treatment Agonists Antagonists* (MAT) Level I: outpatient treatment +/- MAT * Not currently used in Pregnancy 24 24

25 Agonists vs. Antagonists Drug Type Analogy Methadone Full Agonist High Octane Buprenorphine Partial Agonist Low Octane Naltrexone Antagonist Water 25 25

26 BOTTOM LINE: In both controlled and retrospective studies, the success rate for most medications is between 40 and 60% (one to two years). When patients come off the medication, they relapse. Relapse may be associated with an increased chance of overdose and death. Physiology of Addiction 26 26

27 Benefits of Methadone Salsitz, ASAM, 2012 Reduction in death rates (Grondblah, 1990) Reduction in IVDU (Ball & Ross, 1991) Reduction in # of crime days (Ball & Ross) Reduced HIV seroconversion / HCV conversion IMPROVED OUTCOME AFTER INCARCERATION 27

28 Ball 1988: reduction in IVDU ORT: yes or no??? 28 28

29 Ball 1988: reduction in IVDU ORT: yes or no??? 29 29

30 Ball 1988: resumption of IVDU! ORT: yes or no??? 30 30

31 Ball 1988: resumption of IVDU! ORT: yes or no??? 31 31

32 Buprenorphine A partial opiate agonist (less potent) Less analgesic effect Less respiratory depression <100 documented deaths in the U.S. (Soyka); PER YEAR WITH METHADONE Treats both pain and opiate dependency Different formulations are approved Addiction and Pregnancy 32 32

33 Buprenorphine Available in 3 branded forms: Generic buprenorphine (Subutex ): sublingual OFF MARKET: Medicaid may not cover generic due to concerns about diversion. Bunavail : sublingual buprenorphine + naloxone (Narcan ): prevents IV use* Suboxone : sublingual buprenorphine + naloxone (Narcan ): prevents IV use* Zubsolv : ditto ANY of these will precipitate sudden withdrawal: only give when patient is going INTO withdrawal! * not FDA approved for pain Addiction and Pregnancy 33 33

34 Buprenorphine Formulations approved for PAIN: Buprenex : parenteral, used in the hospital setting. Butrans : weekly patch, 10 to 20 mcg/hr Belbuca : buccal film from mcg/24 hr. Addiction and Pregnancy 34 34

35 What Formulation Should You Use? Generic buprenorphine avoids naloxone. It is more susceptible to diversion Use whatever their insurance will pay for!! 35 35

36 Buprenorphine long-term follow up: Fiellin,

37 Concerns about buprenorphine It can be abused (mostly for withdrawal) It is unsafe when combined with sedatives & alcohol. It is an opioid. Relapse rates after detox exceed 90%. (Weiss, 2011) 37 37

38 Vivitrol (injectable naltrexone) for opioid dependence This medication is not currently used during pregnancy; but may be used following delivery. 38

39 Addiction Tx in Russia Kupitsky et al; Lancet 2011; 377:

40 Vivitrol: abstinence 40

41 Vivitrol: craving 41

42 Vivitrol: concerns As with methadone and buprenorphine, when the medication is stopped, relapse may lead to death due to lack of tolerance. Pain management after injectable naltrexone is challenging and may require hospitalization. 42

43 Doc, when can I get off this sh*t medication? Can you detox? 43 43

44 Luty women underwent detox during pregnancy 40 successfully detoxed. No adverse fetal effects documented Luty et al, J Sub Abuse Treat 24 (2003); ORT: yes or no??? 44 44

45 Detoxing During Pregnancy? Luty 2003 Luty women underwent detox during pregnancy 40 successfully detoxed. No adverse fetal effects documented But: only 1/101 patients documented to be abstinent at time of delivery! Luty et al, J Sub Abuse Treat 24 (2003); ORT: yes or no??? 45 45

46 Maintenance vs. Detox? Kakko et al heroin users were started on buprenorphine/naloxone. 20 were detoxed off and offered counseling. 20 were kept on buprenorphine and offered counseling. A year later. ORT: yes or no??? 46 46

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49 Can you taper off buprenorphine without relapse? 49

50 Buprenorphine in opioid dependence 654 patients enroll on buprenorphine for 2 weeks. 50% stay abstinent. They are tapered off and over 90% relapse. 360 remain, they go back on buprenorphine for 12 weeks, 50% stay abstinent. They taper off and 90+% relapse. Moral of the story: medications work as long as you take them. 59

51 Opioid Detox During Pregnancy Bell et al, AJOG 2016; 215: 374.e1-6 Fetal death during pregnancy is rare. Patients can be successfully and safely detoxed. The lowest neonatal abstinence rates are seen with incarcerated patients (19%) and inpatient detox with intensive outpatient treatment (17%) Worst results are inpatient detox without IOP (70%) and buprenorphine outpatient detox (31%) 51

52 Treatment of Opioid Dependence During Pregnancy 52

53 METHADONE the gold standard Was only approved for use for addiction in 1965; Dr. James Wardell started in Detroit in TIP 40: methadone is (was) the preferred treatment in pregnancy. Buprenorphine should be offered ONLY if methadone not available or patient refuses methadone. Buprenorphine was considered experimental. Jones and Johnson: small studies showed promise

54 Maternal Opioid Treatment: Human Experimental Research (MOTHER) 54

55 :NEJM 2010; 363: Addiction and Pregnancy 55 55

56 MOTHER STUDY Double blinded, RCT Methadone vs. buprenorphine Contingency management (financial incentives $$ $$) CBT (cognitive behavioral tx) Transportation, etc. NO polysubstance dependence x tobacco! Addiction and Pregnancy 56 56

57 MOTHER STUDY Patients already on methadone are admitted to research unit for detox. 6 mg MS/mg methadone (4 divided doses) Rescue doses prn Kept until stabilized THIS IS NOT FEASIBLE IN CLINICAL PRACTICE!!!!!!!!! Randomized to study meds on L & D Addiction and Pregnancy 57 57

58 Sites Johns Hopkins, Baltimore MD T. Jefferson Univ., Philadelphia, PA Women & Infants, Providence RI Vanderbilt UMC, Nashville, TN St. Joseph s Hlth Ctr. Toronto, Canada Wayne State Univ., Detroit, Michigan University of VT, Burlington, VT Addiction Clinic Vienna, Au Addiction and Pregnancy 58 58

59 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 59 59

60 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 60 60

61 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 61 61

62 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 62 62

63 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 63 63

64 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 64 64

65 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 65 65

66 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required # of days in hospital Duration of treatment for NAS Birthweight % preterm delivery 19 7* Positive drug screen at delivery 15% 9%* Dropped out 18% 33 Addiction and Pregnancy 66 66

67 MOTHER study. Buprenorphine exposed neonates exhibited fewer stress-abstinence signs, were less excitable less hypertonia better self-regulation and required less handling than methadoneexposed neonates. Jones Finnegan & Kaltenbach Drugs

68 Who should NOT go on buprenorphine? Patients who are: Already on methadone (>35 mg) Active hepatitis C (high LFTs) Unable to engage in treatment Taking benzos Plan on mixing bup with their opiates Are diverting Can t get insurance coverage Addiction and Pregnancy 68 68

69 How do you start buprenorphine? LFT, UDS, informed consent If GA > 24 weeks: monitor on L&D Short acting opioids: 8 to 12 hrs abstinence or moderate withdrawal sx Start buprenorphine DC on 8 to 16 mg bupx sublingual Addiction and Pregnancy 69 69

70 Buprenorphine-->Methadone? NOT necessary! Can continue buprenorphine Risk of NAS is decreased (severity and duration) Addiction and Pregnancy 70 70

71 Methadone à Buprenorphine? Methadone: Has a LONG half life MOTHER study dropouts were due to attempts to convert high dose methadone to buprenorphine Current expert opinion is to limit to patients on mg. Safest course may be to remain on methadone. Addiction and Pregnancy 71 71

72 Current Management: Eleonore Hutzel Recovery Center, Detroit Mich Patients who present on SHORT acting opioids: buprenorphine Patients who present on long acting opioids or methadone: methadone Benzodiazepine use must stop immediately or will be referred to methadone. Failure to remain abstinent: refer to methadone

73 Labor/Surgery in Pregnant Patients on Buprenorphine: Options Planned delivery: convert to short acting opiates and back again Stop buprenorphine, start short acting opioids at any time. Resume buprenorphine after 12 hrs abstinence No opiates, rely on epidural (vag delivery only) Continue treatment with Buprenex SL Buprenorphine/Buprenex have been used postoperatively Addiction and Pregnancy 73 73

74 Epidural Management Middle East J Anesthesiol 2013 Oct; 22(3):

75 Management of Labor/Postpartum in the Recovering Patient Labor may be a trigger for relapse Epidurals should be encouraged Don t discharge patients with short acting opiates whenever possible! For C/S patients: need to involve family, social work, EHRC when dispensing opiates RESIDENTS: Confirm EVERYTHING the patient tells you!! Addiction and Pregnancy 75 75

76 Management of Labor/Postpartum in the Recovering Patient Labor may be a trigger for relapse Epidurals should be encouraged Don t discharge patients with short acting opiates whenever possible! For C/S patients: need to involve family, social work, EHRC when dispensing opiates RESIDENTS: Confirm EVERYTHING the patient tells you!! Addiction and Pregnancy 76 76

77 Management of Labor/Postpartum in the Recovering Patient Labor may be a trigger for relapse Epidurals should be encouraged Don t discharge patients with short acting opiates whenever possible! For C/S patients: need to involve family, social work, EHRC when dispensing opiates RESIDENTS: Confirm EVERYTHING the patient tells you!! Addiction and Pregnancy 77 77

78 Management of Labor/Postpartum in the Recovering Patient Labor may be a trigger for relapse Epidurals should be encouraged Don t discharge patients with short acting opiates whenever possible! For C/S patients: need to involve family, social work, EHRC when dispensing opiates RESIDENTS: Confirm EVERYTHING the patient tells you!! Addiction and Pregnancy 78 78

79 Management of Labor/Postpartum in the Recovering Patient Labor may be a trigger for relapse Epidurals should be encouraged Don t discharge patients with short acting opiates whenever possible! For C/S patients: need to involve family, social work, EHRC when dispensing opiates RESIDENTS: Confirm EVERYTHING the patient tells you!! Addiction and Pregnancy 79 79

80 The Opioid Epidemic & Naloxone (Narcan ) Rescue Developed for Families Against Narcotics 80

81 Naltrexone vs. Naloxone Naltrexone Oral (Rivea ) or IM (Vivitrol ) Slow onset Long acting (hours to weeks) Tightest binding to brain Used for PREVENTION of overdose (FDA) Naloxone IV, IM, SC or IN (Narcan, Evzio ) Rapid Onset Short acting (minutes) Less tightly bound Used for TREATMENT of overdose (FDA) 81 81

82 What Does Narcan NOT Do? It will not reverse an overdose from alcohol, sedatives (Benzodiazepines such as Xanax, Valium and Klonopin), muscle relaxants, or stimulants like Cocaine or Amphetamines. If there is more than one drug involved (usually Benzodiazepines and Opioids), it may partially revive the patient until EMS arrives. 82

83 Naloxone formulations: 83 83

84 Who is at Greatest Risk? Abstinence > 2 weeks: treatment; jail; relapse. Discontinuing MAT: methadone; buprenorphine; Vivitrol (naltrexone). (Volkow 2014: 50% decr in OD deaths with MAT) Mixing opioids with sedatives: alcohol, benzodiazepines, muscle relaxers FENTANYL 84 84

85 OD deaths: heroin and Fentanyl: Washtenaw Co. 75% DUE TO HEROIN +/- FENTANYL; 25% DUE TO PRESCRIPTION PILLS 28 (heroin) 21 (fentanyl + heroin) 12 (pills) (25%) 49 (total) 85

86 Fentanyl on Urine Drug Screen Pregnant Patient 86 86

87 How To Do A Naloxone Rescue (youtube.com -> ccmdphd) Make Sure They are Not Breathing or risk of failure (always) Call 911 Do Rescue Breaths (not compressions) Give Naloxone Resume Rescue Breaths Repeat Naloxone every 2-3 mins 87 87