Pregnancy and Addiction 1

Transcription

1 Disclaimers Addiction and Pregnancy 2017 Carl Christensen, MD, PhD, D-FASAM Clinical Assoc Prof, Psychiatry and OB/Gyn, Wayne State Univ School of Med, Detroit Mi Medical Director, Mich Health Professional Recovery Program June 15, 2017 No Financial Relationships Consultant, DEA/DOJ Consultant, BCBS Mich Methadone provider, Wayne State SOM Medical Director, Dawn Farm, Ann Arbor, MI Buprenorphine and naltrexone provider, A2 3 Qualifications: Carl Christensen Disclosures II Medications will be referred to in the generic whenever possible; will discuss FDA specific formulations We will be discussing off label use of buprenorphine and methadone; neither of these are approved by the FDA for use of opioid dependence in pregnancy WHY TALK ABOUT THIS? WHY TALK ABOUT THIS? Addiction and Pregnancy 11 Addiction and Pregnancy 12 Pregnancy and Addiction 1

2 WHY TALK ABOUT THIS? WHY TALK ABOUT THIS? NAS in Michigan You are here.. HEROIN Addiction and Pregnancy 13 Addiction and Pregnancy 16 NAS OPIOID USE rural Urban JAMA Pediatrics December 12, 2016 Online What is Addiction? 20 What is Addiction? Physiologic Dependence? Lack of willpower? An amoral condition? A brain disease? Pregnancy and Addiction 2

3 21 Physiologic Dependence: Tolerance and Withdrawal Tolerance: requiring increasing amounts of drug to get the same effect Withdrawal: the opposite effect of the drug when it is removed NEITHER of these imply chemical dependency (addiction) Lack of Willpower? 22 An amoral condition? Brain disease? 25 The Nucleus Accumbens: the Pleasure Center. Dopamine: the Pleasure DRUG 26 VTA: the gas tank : supplies dopamine to the Nucleus Accumbens Pregnancy and Addiction 3

4 Frontal Cortex: inhibits the What is the problem? Pleasure Center (maybe) Addiction is not a problem of drug WITHDRAWAL What is the problem? Drug WITHDRAWAL: the Hindbrain Addiction is not a problem of drug WITHDRAWAL.. It is a problem of: CRAVING LOSS OF CONTROL COMPULSIVE USE USE DESPITE CONSEQUENCES (the 4 Cs ) 31 Drug ADDICTION: the (primitive) Forebrain: 33 Pregnancy and Addiction 4

5 39 Why Can t Addicts Stop????? The relapse rate after undergoing detox approaches 100% The relapse rate when coming off meds (buprenorphine, methadone) is 90% But: their withdrawal is gone. SO: why do they relapse????? 40 Normal Volunteers Red: good blood flow Non users Cocaine users, 10 days sober Cocaine Users, 100 days sober High blood flow Low blood flow [C-11]d-threo-methylphenidate How Long to recover from Methamphetamine? Normal Control Methamphetamine Abuser (1 month abstinent) high low Treatment of Opioid Dependence (without) Pregnancy Methamphetamine Abuser (14 months abstinent) Volkow et al., J. Neuroscience, Medication Assisted Therapy (MAT): Agonists vs. Antagonists Drug Type Analogy Methadone Full Agonist High Octane Buprenorphine* Partial Low Octane Agonist Naltrexone Antagonist Water Medication Assisted Therapy (MAT): Methadone Pregnancy and Addiction 5

6 Medication Assisted Therapy (MAT buprenorphine Medication Assisted Therapy (MAT naltrexone BOTTOM LINE: (non-pregnant) 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. 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 59 Ball 1988: reduction in IVDU Ball 1988: reduction in IVDU ORT: yes or no??? 61 ORT: yes or no??? 62 Pregnancy and Addiction 6

7 Ball 1988: resumption of IVDU! Ball 1988: resumption of IVDU! ORT: yes or no??? 63 ORT: yes or no??? 64 Problems with methadone Buprenorphine Requires initial daily dosing first 90 days. Must be clean for 2 years before you can increase take homes! Methadone clinics may be a source of wet faces and wet places Stigma Judges will often try and force moms off methadonenow forbidden by the feds. 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 66 Buprenorphine +/-Naloxone: 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 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. ANY of these will precipitate sudden withdrawal: only give when patient is going INTO withdrawal! Addiction and Pregnancy 67 * not FDA approved for pain Addiction and Pregnancy 68 Pregnancy and Addiction 7

8 What Formulation Should You Use? Buprenorphine long-term follow up: Fiellin, 2008 Generic buprenorphine avoids naloxone. It is more susceptible to diversion Use whatever their insurance will pay for!! 69 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) Vivitrol (injectable naltrexone) for opioid dependence This medication is not currently used during pregnancy; but may be used following delivery. 71 Addiction Tx in Russia Vivitrol: abstinence (50%) Kupitsky et al; Lancet 2011; 377: C / Pregnancy and Addiction 8

9 No Vivitrol, Control Treatment (40%) No Vivitrol; No Treatment (0%) Due to Vivitrol (naltrexone) Due to treatment Why the handcuffs? Vivitrol: craving CONTROL VIVITROL Vivitrol: craving Vivitrol: concerns CONTROL VIVITROL As with methadone and buprenorphine, when the medication is stopped, relapse may lead to death due to lack of tolerance. It would be very difficult to treat acute pain while on Vivitrol : suggestion is 20x normal dose. Ex: a patient underwent emergency operative laparoscopy 2 weeks after Vivitrol injection. He was treated with IV Dilaudid, 10 to 20 mg/hr. Pregnancy and Addiction 9

10 Luty 2003 Doc, when can I get off this sh*t medication? Can you detox off MAT? 101 women underwent detox during pregnancy 40 successfully detoxed. No adverse fetal effects documented BUT: Luty et al, J Sub Abuse Treat 24 (2003); ORT: yes or no??? 83 Maintenance vs. Detox? Kakko et al heroin addicts were started on buprenorphine/naloxone. 20 were detoxed off and offered counseling. 20 were kept on buprenorphine/naloxone and offered counseling. A year later. ORT: yes or no??? ORT: yes or no??? Can you taper off buprenorphine without relapse? 87 ORT: yes or no??? Pregnancy and Addiction 10

11 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. Your Baby Will Die If You Detox : Opioid Detox During Pregnancy Fetal death during pregnancy is rare. Patients can be successfully and safely detoxed. The lowest neonatal abstinence rates are seen with incarcerated patients (19%). Bell et al, AJOG 2016; 215: 374.e1-6 What is the Risk of Dying in and out of Treatment? Relative Risk= the risk of dying compared to someone who does NOT have opioid addiction RR= 1 without addiction. If RR >1 you are more likely to die. Mortality and M.A.T (bup and MTD) 122, 885 patients: OD mortality NO ADDICTION: RELATIVE RISK IS ONE (1) METHADONE BURPENORPHINE In treatment Out of treatment In Treatment Out of Treatment Sordo L et al. Mortality Risk during and after opioid substitution treatment: systematic review and meta0analysis of cohort studies. BMJ 2017; 357: J1550 Take Home Points: Mortality appears to decrease (29%) after starting medication assisted treatment. Mortality INCREASES after leaving treatment. Both the first two weeks IN treatment (methadone ) and OUT of treatment (methadone and buprenorphine) are the most dangerous periods. Treatment of Opioid Dependence During Pregnancy Pregnancy and Addiction 11

12 101 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 was considered experimental. Improvement in neonatal outcomes documented by Ed Johnson and Andre Jones. Maternal Opioid Treatment: Human Experimental Research (MOTHER) MOTHER STUDY :NEJM 2010; 363: Addiction and Pregnancy 103 Double blinded, RCT Methadone vs. buprenorphine Contingency management (financial incentives $$$$) CBT (cognitive behavioral tx) Transportation, etc. NO polysubstance dependence x tobacco! Addiction and Pregnancy 104 MOTHER STUDY Sites 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 Johns Hopkins, Baltimore MD T. Jefferson Univ., Philadelphia, PA Women & Infants, Providence RI Vanderbilt UMC, Nashville, TN St. Josephʼs Hlth Ctr. Toronto, Canada Wayne State Univ., Detroit, Michigan University of VT, Burlington, VT Addiction Clinic Vienna, Austria Addiction and Pregnancy 105 Addiction and Pregnancy 106 Pregnancy and Addiction 12

13 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 MOTHER study. Buprenorphine exposed neonates exhibited fewer stress-abstinence signs, were less excitable less hypertonia better selfregulation and required less handling than methadone-exposed neonates. Jones Finnegan & Kaltenbach Drugs 2012 Addiction and Pregnancy 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 Buprenorphine-->Methadone? NOT necessary! Can continue buprenorphine Risk of NAS is decreased (severity and duration)with buprenorphine as compared to methadone! Again, neither of these is APPROVED for treatment of opioid dependence during pregnancy. Addiction and Pregnancy 116 Addiction and Pregnancy 118 Methadone à Buprenorphine? Methadone: Has a LONG half life MOTHER study dropouts were partially 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 119 Current Management: Eleonore Hutzel Recovery Center/ Tolan Clinic, 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 they will be referred for methadone. 120 Pregnancy and Addiction 13

14 Management of Labor/Postpartum in the Recovering Patient Labor may be a trigger for relapse Epidurals should be encouraged Donʼt discharge patients with short acting opiates whenever possible! For C/S patients: need to involve family, social work, addictionist when dispensing opiates RESIDENTS: Confirm EVERYTHING the patient tells you!! 136 Who is Behind the Opioid Epidemic? Addiction and Pregnancy 135 Unintentional overdose deaths involving opioid analgesics parallel per capita sales of opioid analgesics in morphine equivalents by year, U.S., Rates of Opioid Sales, OD Deaths, and Treatment, Opioid Sales KG/10,000 Opioid Deaths/100,000 * Number of Opioid sales 600 Deaths (mg/person) '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 Source: National Vital Statistics System, multiple cause of death dataset, and DEA ARCOS Rate sales deaths treatment 1999 CDC. MMWR Year * 2007 opioid sales figure is preliminary. 139 Michigan is 10 th in the US: 140 WHY do doctors over prescribe? 107 prescriptions/100 people. The Four D s: Dated Dishonest Duped Disabled Pregnancy and Addiction 14

15 141 The Four D s: 142 The Four D s: Dishonest? Dated Disabled Duped Dishonest? Dated Disabled Duped 143 The Four D s: 144 The Four D s: Dishonest? Dated Disabled Duped Dishonest? Dated Disabled Duped Pressure on Doctors? 146 The Four D s: Dishonest Dated Disabled Duped The 5 th D: defamation Baker D. History of The Joint Commission s Pain Standards: Lessons for Today s Prescription Opioid Epidemic. JAMA, published online February 23, by 2004 this phrase was deleted from the accreditation standards manual. Lembke, Anna. Why Doctors Prescribe Opioids to known Opioid Abusers. n engl j med 367;17 nejm.org october 25, 2012 Pregnancy and Addiction 15

16 152 Naltrexone vs. Naloxone The Opioid Epidemic & Naloxone (Narcan ) Rescue Developed for Families Against Narcotics 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) Naloxone formulations: (0.4 mg) 154 Intranasal (I.N.): ADAPT (4mg/2mg!) Who is at Greatest Risk? 156 Fentanyl on Urine Drug Screen Pregnant Patient Abstinence > 2 weeks: treatment; jail; relapse. Discontinuing MAT: methadone; buprenorphine; Vivitrol (naltrexone). Mixing opioids with sedatives: alcohol, benzodiazepines, muscle relaxers FENTANYL 50% of UDS samples with heroin are pos for Fentanyl Pregnancy and Addiction 16

17 157 How To Do A Naloxone Rescue Naloxone in Pregnancy Make Sure They are Not Breathing (always) Call 911 Do Rescue Breaths (not compressions) Give Naloxone Resume Rescue Breaths Repeat Naloxone every 3 mins To review videos: go to ccmdphd on YouTube due to the risk of induced withdrawal, use of naloxone should be avoided during pregnancy and used only when absolutely necessary ASAM textbook of addiction medicine Naloxone in Pregnancy That statement is no longer operative. Ron Ziegler, President Nixon s Press Secretary Contact Information: Carl Christensen Office Cell: Website: Pregnancy and Addiction 17