Disclaimers. Opioid Dependence: Before, During and After Pregnancy WHY TALK ABOUT THIS? WHY TALK ABOUT THIS? WHY TALK ABOUT THIS?

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: Before, During and After Pregnancy Carl Christensen, MD, PhD, FASAM, FACOG Past President, Mich Society Addiction Medicine Medical Director, Eleonore Hutzel Recovery Center, DMC Clinical Associate Professor, WSU Pain Recovery Solutions Ann Arbor, MI Disclaimers Consultant, PCSS Consultant, DEA/ DOJ Consultant, BCBS Speaker, Reckitt Benckiser Methadone provider, WSU Former: Medical Director, Dawn Farm WHY TALK ABOUT THIS? James Wardell, MD Medical Director, Eleonore Hutzel Recovery Center (EHRC) 1969-2004 Addiction and Pregnancy 3 Addiction and Pregnancy 4 WHY TALK ABOUT THIS? WHY TALK ABOUT THIS? Addiction and Pregnancy 5 Addiction and Pregnancy 6 Carl Christensen, MD PhD 1

What is Addiction? What is Addiction? Physiologic Dependence? Lack of willpower? An amoral condition? A mental illness? Physiology of Addiction 9 Physiologic Dependence: Tolerance and Withdrawal The Nucleus Accumbens: GO!!! 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) Physiology of Addiction 10 Physiology of Addiction 14 VTA: the gas tank : supplies dopamine to the Nucleus Accumbens Frontal Cortex: STOP!!!! Physiology of Addiction 15 Physiology of Addiction 16 Carl Christensen, MD PhD 2

What is Addiction? What is Addiction? Addiction is not a problem of drug WITHDRAWAL.. It is a problem of: CRAVING LOSS OF CONTROL COMPULSIVE USE USE DESPITE CONSEQUENCES 17 19 WHY CAN T ADDICTS STOP? I feel like I don t belong in my own skin. anonymous alcoholic Decreased Dopamine receptors =decreased Dopamine = Decreased Hedonic Tone Salsitz 2006 Physiology of Addiction 21 Grand Physiology Rounds of Hutzel Addiction 4 17 07 26 26 SAFETY OF OPIOIDS IN CHRONIC PAIN MANAGEMENT Are opioids the culprit? Risks factors in opioid deaths in WV HALL et al, JAMA Dec 10 2008; 300; 22: 2613 Risk Factor History of drug abuse 78 Any diverted meds 63 Nonmedical route 22 5 Providers 21 Alcohol 17 History of previous OD 17 Illicit drug (Coc, H, meth) 16 Currently enrolled in OTP 4 Percentage involved 36 ANY INDICATOR 95 37 Carl Christensen, MD PhD 3

Are opioids the culprit? Risks factors in opioid deaths 4 prescriptions, 4 providers; dead from overdose...opioid analgesics were involved in 75% of pharmaceutical overdose deaths; benzodiazepines were also involved in 29% of such deaths. Benzodiazepines were also involved in 30% of opioid-related deaths-far more than any other class of drugs. This indicates that combining benzos and opioids may be especially dangerous http://www.psychiatrictimes.com/psychopharmacology/benzodiazepines-and-pain 38 40 WHY do doctors over prescribe? The Four D s: Dated Dishonest Duped Disabled 42 Addiction and Pregnancy 43 How to Report Allegation Unit Bureau of Health Care Services P.O. Box 30454 Lansing, 48909 (517) 373-9196 Michigan Health Professionals Recovery Program 1-800-453-3784 ADDICTION PAIN How do you recognize when you are fueling addiction rather than treating pain? Making the Diagnosis 46 47 Carl Christensen, MD PhD 4

Techniques to Evaluate for signs of addiction in your pain patient Techniques to Evaluate for signs of addiction in your pain patient Review of Medical Records (refusal?) Physical exam: Stigmata of addiction: nicotine, opiates, cocaine Obvious intoxication/withdrawal UDS MAPS Family interviews Multiple visits, evaluate for reliability Review of Medical Records (refusal?) Physical exam: Stigmata of addiction: nicotine, opiates, cocaine Obvious intoxication/withdrawal UDS MAPS Family interviews Multiple visits, evaluate for reliability 48 49 Techniques to Evaluate for signs of addiction in your pain patient Urine Drug Screens Review of Medical Records (refusal?) Physical exam: Stigmata of addiction: nicotine, opiates, cocaine Obvious intoxication/withdrawal UDS MAPS Family interviews Multiple visits, evaluate for reliability Check for meds that you have been prescribing. (missing meds = malingering) Check for meds that indicate abuse (MJ, cocaine) = addiction Remember your medication may not show up (methadone, fentanyl, suboxone) TELL THE PATIENT YOU ARE TESTING THEM FOR SAFETY S SAKE TELL THEM YOU PRACTICE UNIVERSAL SCREENING! 50 51 Techniques to Evaluate for signs of addiction in your pain patient Michigan Automated Prescription System (MAPS) Review of Medical Records (refusal?) Physical exam: Stigmata of addiction: nicotine, opiates, cocaine Obvious intoxication/withdrawal UDS MAPS Family interviews Multiple visits, evaluate for reliability A 23 year old was transferred from Midland for a complicated pregnancy termination. Successful dilation and evacuation was performed under laparoscopic guidance. Postoperatively, the patient complained of severe pain, prompting workup for bowel perforation. The patient requested high doses of IV Dilaudid for pain control. 52 53 Carl Christensen, MD PhD 5

Techniques to Evaluate for signs of addiction in your pain patient Review of Medical Records (refusal?) Physical exam: Stigmata of addiction: nicotine, opiates, cocaine Obvious intoxication/withdrawal UDS MAPS Family interviews Multiple visits, evaluate for reliability 54 55 Techniques to Evaluate for signs of addiction in your pain patient How do you make the diagnosis of addiction? Review of Medical Records (refusal?) Physical exam: Stigmata of addiction: nicotine, opiates, cocaine Obvious intoxication/withdrawal UDS MAPS Family interviews Multiple visits, evaluate for reliability Rule out a pure pain diagnosis You can have both!!!! Rule out malingering (selling) Use the DSM IV criteria or the 4 C s: (Craving, Compulsion, loss of Control & use despite Consequences) Keep asking yourself if you made the right diagnosis 56 57 Doctor, am I going to become addicted? Overall: the incidence of iatrogenic addiction in the chronic pain patient is low. The initial estimate was 1/1000!!! BUT: The incidence of addiction in the chronic pain population is similar to the general population (15%). SO: EXPECT >5% OF YOUR PATIENTS TO SHOW ABERRANT BEHAVIOR ADDICTION PAIN What do you do when you realize you are fueling addiction rather than treating pain? Aronoff, 2000; Heit, 2004; Porter, 1980 58 59 Carl Christensen, MD PhD 6

Do NOT continue to prescribe! TREATMENT OF ADDICTION Impression: Opioid dependence Plan: Methadone 10 mg tabs, #240, return one month. Behavioral: counseling Spiritual: 12 step meetings Surgical: gastric bypass surgery MEDICAL 60 Physiology of Addiction 61 Agonists vs. Antagonists BOTTOM LINE: Drug Type Analogy Methadone Full Agonist High Octane Buprenorphine Partial Agonist Low Octane Naltrexone Antagonist Water 64 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 65 Ball 1988: reduction in IVDU Ball 1988: resumption of IVDU! ORT: yes or no??? 67 ORT: yes or no??? 68 Carl Christensen, MD PhD 7

Buprenorphine ( Suboxone ) Buprenorphine A partial opiate agonist (less potent) Less analgesic effect Less respiratory depression <100 documented deaths in the U.S. (Soyka); 4000+ PER YEAR WITH METHADONE Treats both pain and opiate dependency Different formulations are approved Available in 3 forms: Burpenex : injectable Subutex : sublingual buprenorphine* OFF MARKET Suboxone : sublingual buprenorphine + naloxone (Narcan ): prevents IV use* Will precipitate sudden withdrawal: only give when patient is going INTO withdrawal! * not FDA approved for pain Addiction and Pregnancy 72 Addiction and Pregnancy 73 Buprenorphine long-term follow up: Fiellin, 2008 Concerns about Suboxone 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) 75 Doc, when can I get off this sh*t medication? Can you detox? 101 women underwent detox during pregnancy 40 successfully detoxed. No adverse fetal effects documented Luty et al, J Sub Abuse Treat 24 (2003); 363-367 81 ORT: yes or no??? 82 Carl Christensen, MD PhD 8

Detoxing During Pregnancy? Luty 2003 101 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); 363-367 ORT: yes or no??? 83 Maintenance vs. Detox? 40 heroin addicts were started on Suboxone. 20 were detoxed off and offered counseling. 20 were kept on Suboxone and offered counseling. A year later. ORT: yes or no??? 84 85 ORT : yes or no??? 86 ORT : yes or no??? Treatment of Opioid Dependence During Pregnancy Maternal Opioid Treatment: Human Experimental Research (MOTHER) Carl Christensen, MD PhD 9

MOTHER STUDY MOTHER STUDY Double blinded, RCT Methadone vs. buprenorphine Contingency management (financial incentives) CBT Transportation, etc. NO polysubstance dependence x 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 tobacco! Addiction and Pregnancy 90 Addiction and Pregnancy 89 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, Austria Addiction and Pregnancy 91 Addiction and Pregnancy 92 Methadone vs. Buprenorphine: the MOTHER study Measure Methadone Buprenorphine Amount of MS required 10.4 1.1 # of days in hospital 17.5 10 Duration of treatment for NAS 9.9 4.1 Birthweight 2878 3093 % 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 self-regulation and required less handling than methadone-exposed neonates. Jones Finnegan & Kaltenbach Drugs 2012 Addiction and Pregnancy 93 94 Carl Christensen, MD PhD 10

Who should NOT go on buprenorphine? Patients who are: How do you start buprenorphine? Already on methadone (>35 mg) Unable to engage in treatment Taking benzos Plan on mixing bup with their opiates Are diverting Can t get insurance coverage Addiction and Pregnancy 95 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 buprenex 0.3 mg IM q 6 scheduled Switch to 2 4 mg bupx sublingual DC on 8 to 16 mg bupx sublingual Addiction and Pregnancy 96 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 25 50 mg. Safest course may be to remain on methadone. 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 98 Addiction and Pregnancy 99 MARIJUANA AND PREGNANCY MARIJUANA AND PREGNANCY Addiction and Pregnancy 100 Occasional MJ use does not appear to affect birthweight, gestational age, etc. Heavy (weekly) users had babies with decreased birthweight. Babies MAY have shown withdrawal type symptoms at birth. No increase in abruption, SIDS, etc that you do see in tobacco addiction. Addiction and Pregnancy 101 Carl Christensen, MD PhD 11

MARIJUANA AND PREGNANCY MARIJUANA AND PREGNANCY ADOLESCENT use is associated with: Increased in schizophrenia (2x) Decreased IQ scores (8 points!) Congnitive deficits. Increase in psychiatric co morbidity Addiction and Pregnancy 102 Medical MJ is not (automatically) recognized by CPS. Referral and interventions may still occur. Medical MJ does not invalidate an addiction evaluation. Medical MJ does not prevent criminal prosecution for MVA, etc. Addiction and Pregnancy 103 Tobacco and Pregnancy Tobacco and Pregnancy Tobacco is a major cause of statistics Herb Malinoff, MD Addiction and Pregnancy 105 Addiction and Pregnancy 106 Tobacco and Pregnancy Associated With: Low Birth Weight (LBW) Small for Gestational Age (SGA) Miscarriage Stillbirth SIDS Congenital anomalies* Difficulty Breastfeeding Addiction and Pregnancy 107 What works for tobacco cessation? (everyone) Counseling NRT Buproprion (Wellbutrin, Zyban) Buproprion + NRT Varenicline (Chantix) Addiction and Pregnancy 108 Carl Christensen, MD PhD 12

What works for tobacco cessation in pregnancy? Treatment Counseling NRT Buproprion (Zyban, Wellbutrin SR) Varenicline (Chantix) Outcome 14 vs 6 abstinent No success in pregnant women 45% vs 14% abstinent No data in pregnancy, 40+% success in nonpregnant patient. Addiction and Pregnancy 109 EHRC These medications are mostly category C: birth defects cannot be ruled out. Tobacco is Category X ( same as plutonium ) NRT, Buproprion and Varenicline are offered to all patients in 2 nd / 3 rd trimester. Addiction and Pregnancy 110 Management of Labor/Postpartum in the Recovering Patient 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 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!! the patient tells you!! Addiction and Pregnancy Addiction and Pregnancy 112 111 Management of Labor/Postpartum in the Recovering Patient 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 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!! the patient tells you!! Addiction and Pregnancy Addiction and Pregnancy 114 113 Carl Christensen, MD PhD 13

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 115 Is there Recovery after Delivery? Is There Recovery After Delivery? Is There Recovery After Delivery? Relapse rates on tobacco are up to 85% after delivery. Normal relaspe rates for drugs and alcohol at one year are 40 to 60% for successful treatment. There is no evidence that a newborn is protective against relapse. The stressors of a newborn may predispose to relapse. Addiction and Pregnancy 119 Pregnancy is felt to be a window of opportunity in addiction treatment Often described as a gun to the head by the patient Patients are faced with loss of custody (of ALL children) if they test positive If they do not succeed, prognosis felt to be hopeless Addiction and Pregnancy 121 Is There Recovery After Delivery? Is There Recovery After Delivery? Addiction and Pregnancy 122 Addiction and Pregnancy 123 Carl Christensen, MD PhD 14

Why Treat Addiction? Drug Dependence, a Chronic Medical Illness: McLellan 2000 Only about 40% of patients will be abstinent at one year after treatment. Failure rates may be due to lack of aftercare, often due to insurance difficulties Low economic status, psych comorbidity and lack of family/social supports also predict relapse. Relapse is often viewed as inevitable and drug dependence as hopeless * 124 125 Drug Dependence, a Chronic Medical Illness: McLellan 2000 Chronic, Treatable but Incurable Diseases ONLY 60% OF TYPE I DIABETICS ADHERE TO MEDICATION SCHEDULE LESS THAN 40% OF ASTHMATICS ADHERE TO TREATMENT REGIMEN LESS THAN 40% OF HYPERTENSIVES ADHERE TO THEIR TREATMENT REGIMEN DRUG DEPENDENCE =40 TO 60% ADHERENCE Obesity Hypertension Diabetes Asthma Addiction 126 Physiology of Addiction 128 Contact info: Carl Christensen YOUTUBE.COM: ccmdphd ccmdphd@mac.com Cell: 313 510 9496 Voice mail: 734 448 0226 Pain Recovery Solutions (A2): 734 434 6600 Physiology of Addiction 130 Carl Christensen, MD PhD 15