Pregnancy & Addiction for Labor and Delivery

1. Pregnancy & Addiction for Labor and Delivery Stacy Seikel, MD Medical Director The Center For Drug-Free Living, Inc.

2. DISCLAIMERStacy Seikel, MD • Medical Director, The Center for Drug-Free Living, Inc., Orlando, FL • Member: ASAM, FSAM, AMA, FMA, OCMS • Officer/ Board Positions: FSAM/FMPG • Board Certified, Addiction Medicine, Anesthesiology • Medical Review Officer (MRO) • Speakers Bureau: Reckitt Benckiser, Forrest, Alkermes • Some slides borrowed from Reckitt Benckiser, Sanford Silverman, MD, Berndt Wollschlaeger, MD

3. OBJECTIVES • Understand Specific Problems of Pregnant Women with Addiction • Manage Perioperative Pain Appropriately in Methadone and Buprenorphine Maintained Pregnant Patients • Review the Treatment Needs of Opiate Dependent Pregnant Women and their Newborns

4. Outline • Alcohol & Drug Addiction in Pregnancy • Definition of Addiction • Aberrent Drug Related Behavior • Benzodiazepine • Opiate Maintenance Therapy in Pregnancy • Methadone • Buprenorphine • Perioperative Pain Management for Pregnant Women on Buprenorphine • Perioperative Pain Management for patients on methadone • Breastfeeding • Neonatal Abstinence Syndrome

5. How Prevalent is drug and alcohol use in pregnancy? • 12-24% of women use drugs and alcohol during pregnancy • 1 of every 3-4 women expose fetus to alcohol • Alcohol and tobacco > illicit drugs and prescription drugs • Prevalence in public clinic=private practice • Caucasians > African Americans > Hispanic • No significant variation by socioeconomic status

6. Risk Factor: Family History and Social Situation • Often have a family history of addiction • Exposed to parental violence as children • Experienced emotional, physical, sexual abuse as children • More likely to have a family history of mental illness, particularly in their mothers • More likely to live with a violent, addicted partner

7. Clues in the medical history • No prenatal care – • May be because of fear of discovery of addiction • May be secondary to general chaos in her life • Tattoos or self scarring • Secondary to IVDU or skin popping • Burns on hands and clothing • Nicotine abuse • Hep C +

8. Screening • All pregnant women should be screened for drug and alcohol use • T-ACE • TWEAK • A positive screen indicates the need for a further evaluation • Elements of the history and physical may indicate need for a urine drug screen • On site 11 panel UDS recommended • Immunoassay = screen • GC/MS = confirmatory

9. Drug Screens • Onsite urine drug screens AKA Point of Care (POC-UDS) • Inexpensive ($5/11 panel) • Immunoassay (same as lab) • Immediate Results • Billable to insurance • May still send to lab for GC/MS or LC/MS/MS confirmation, if needed.

10. Point of Care UDS • Opiates: naturally occurring only(“OPI” on strip or cup) tests for: • Morphine • Codeine • Heroin • Hydromorphone −> Morphine • Hydrocodone −> Codeine

11. Point of Care UDS (Cont.) • All other synthetic and semi-synthetics opiates need a separate immunoassay (a separate test/strip), i.e.: • Oxycodone-OXY • Methadone-MTD • Buprenorphine-BUP • Propoxyphene-PPX • Fentanyl (not available on POC) POC’s are screening tools with false positives and false negatives (need GC/MS or LC/MS/MS to confirm positives and negatives)

12. Treatment Barriers • Fear, shame, and guilt about use • Will she lose other children if in treatment? • Does she have family support? • Attitudes of medical providers • Lack of comprehensive clinical care services for all the problems of pregnancy AND addiction • Can she get to treatment? Transportation problems? • Lack of childcare while in treatment • Basic needs must be met for her to engage in treatment • Co-morbid diagnosis impacting ability to access services • Difficulty addressing many issues simultaneously • Depression, anxiety • Personality Disorder • Immaturity/lack of coping skills

13. Alcohol • Alcohol is a known teratogen • There is NO safe level of drinking in pregnancy • 25-30% of pregnant women expose the fetus to alcohol; fewer consume quantities known to be dangerous • Alcohol exposure in pregnancy is the leading preventable cause of neurobehavioral problems and mental retardation • Alcohol crosses the placental barrier and is poorly metabolized by the fetal liver • Levels of alcohol are found in amniotic fluid after only one drink – double that of maternal serum • Urine ETG – picks up alcohol use past 72 hrs. • Urine ETOH test - worthless

14. New Alcohol Biomarker in Cord Blood • Phosphatidylethonal- PEth • 3-4 week retrospective window for alcohol consumption

15. Medical Complications of Drug Abuse in Pregnancy • Intravenous Drug Use • Bacteremia; Endocarditis • Sexually Transmitted Diseases: • Hepatitis (acute, chronic) • HIV • Malnutrition • Pneumonia • Tetanus • Tuberculosis • Urinary Tract Infections • Endocrine Abnormalities ( decreased ACTH, adrenal function, and ovulation)

16. Obstetrical ComplicationsOpiate Abuse • Remember the polysubstance abuse is the norm….. • Increase in spontaneous abortion, especially first trimester • Amnionitis • Intrauterine Growth Retardation • Placental insufficiency • Postpartum hemorrhage • Pre-eclampsia and eclampsia • Premature labor/premature rupture of membranes • Septic thrombophlebitis

17. Opioid Dependence (DSM-IV) – AKA Addiction(3 or more within one year) • Tolerance • Withdrawal • Larger amounts/longer period than intended • Inability to/persistent desire to cut down or control • Increased amount of time spent in activities necessary to • obtain opioids • Social, occupational and recreational activities given up or reduced • Opioid use is continued despite adverse consequences

18. Addiction • … a primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing the development and manifestations. It is characterized by behaviors that include one or more of the following: • Impaired control over drug use • Compulsive use • Continued use despite harm • Craving • (ASAM, 2001)

19. What Addiction Isn’t:Physical Dependence • Pharmacologic effect characteristic of opioids • Withdrawal or abstinence syndrome manifest on abrupt discontinuation of medication or administration of antagonist • Assumed to be present with regular opioid use for days-to-weeks • Becomes a problem if: • Opioids not tapered when pain resolves • Opioids are inappropriately withheld

20. What Addiction Isn’t:Tolerance • Pharmacologic effect characteristic of opioids • Need to increase dose to achieve the same effect or diminished effect from same dose • Tolerance to various opioid effects occurs at differential rates • Tolerance to non-analgesic effects often beneficial to patients (sedation, respiratory depression) • Analgesic tolerance is rarely the dominant factor in the need for opioid • Patients requiring dose escalation most often have a change in pain stimulus (disease progression, infection, etc.) (Foley, 1991)

21. Addiction • Compulsive Use • Loss of control • Continued use despite adverse consequences

22. “Pseudo-Addiction” • Pattern of drug seeking behavior of pain patients receiving inadequate pain management that can be mistaken for addiction • Cravings and aberrant behavior • Concerns about availability • “Clock-watching” • Unsanctioned dose escalation • Resolves with reestablishing analgesia Weissman, DE, Haddox, JD. Opioid pseudo addiction-an latrogenic syndrome. Pain 1989, 36-363.

23. What is the Risk of Addictionand Aberrant Behavior? • Boston collaborative Drug Surveillance Project: Porter and Jick, 1980. NEJM. • 4 cases of addiction in 11,882 patients with no prior history of abuse who received opioids during inpatient hospitalization. • Dunbar and Katz, 1996, JPSM. • 20 patients with both chronic: pain and substance abuse problems on chronic opioid therapy • Nine out of 20 abused medication • Of the 11 who did not abuse the medications, all were active in recovery programs with good family support

24. Spectrum of Risk of Addiction or Aberrant Behavior ~ 45% <1 % HIGH Long-term Exposure to Opioids in Addicts, Dunbar and Kafz LOW Short-term Exposure to Opioids in Non-addicts Porter and Jick Where is your patient ?

25. Differential Diagnosis of Aberrant Drug-Taking Attitudes and Behavior • Addiction • Pseudo-addiction (inadequate analgesia) • Other psychiatric diagnosis • Encephalopathy • Borderline personality disorder • Depression • Anxiety • Criminal Intent (Passik & Portenoy 1996)

26. Aberrant Drug-taking Behaviors: The Model • Probably less predictive • Aggressive complaining about need for higher doses • Drug hoarding during periods of reduced symptoms • Requesting specific drugs • Acquisition of similar drugs • Unsanctioned dose escalation 1-2 times • Unapproved use of the drug to treat another symptom • Reporting psychic effects not intended by the clinician • Probably more predictive • Selling prescription drugs • Prescription forgery • Stealing or borrowing another patient’s drugs • Injecting oral formulation • Obtaining prescription drugs from non-medical sources • Concurrent abuse of related illicit drugs • Multiple unsanctioned dose escalations • Recurrent prescription losses • Multiple ED visits for acquisition of pain meds Passik and Portency, 1998

27. Opioid Addiction • Opioid addiction is a chronic, progressive, relapsing medical condition • Profound neurobiologic changes accompany the transition from opioid use to opioid addiction • Pharmacologic treatments are effective in normalizing the neurobiologic status, decreasing illicit opioid use, medical and social complications

28. Drug Addiction is a brain disease that affects behavior.

30. Remember: • Limbic system in overdrive • Prefrontal cortex not working • “You have to use to survive.”

31. Benzodiazepines • Disinhibiting effects, like alcohol, can contribute to aggressive behavior • Even short-term use at prescribed doses can be associated with an increased risk for cognitive problems, particularly in the elderly • Does NOT fix the depression &/or anxiety symptoms – “a temporary bandaid”

32. Benzodiazepines • Often used by substance abusers to alleviate unwanted effects of other drugs they have taken • Called an anxiolytic by DSM-IV and “pill form alcohol” or “freeze dried alcohol” by the addictionologists • Acute intoxication can result in accidental injury or death (especially when combined with alcohol/opioids)

33. Problems withChronic BZD Use • Can NOT tell who will become dependent and who will not • Many anxiety disorders are ‘created’ by alcohol and drug use • Not appropriate for long-term use for sleep disorders

34. Problems WithChronic BZD Use • Patients can have physical dependency from chronic therapeutic use • Patients who stop chronic BZD use often develop rebound symptoms of anxiety which may be withdrawal symptoms or a reoccurrence of the symptoms for which the BZD was originally prescribed

35. Risk of OD • 84% of all methadone related deaths had benzos in their system • 100% of buprenorphine related deaths had benzos in their system

36. Rule Out Physical Dependence with Benzos, by asking the following questions (in this order): • “Do you drink alcohol?” If yes, then “How many days out of the last 30?” • “How many days out of the last 30 have you taken benzos?” • “When was the last time you went 4-5 days without taking any?” • “Were you drinking alcohol on those days?” • “What happens when you run out?” (Do not say “Do you run out?” Assume they do.) • “Have you ever had a seizure?”

37. DON’T FEED THE BEARS!!!!!

38. Benzo Prescribers Waiting Room • W

39. Various Discipline See the Maternal Fetal Dyad Differently • Obstetricians • Therapists • Addiction Specialists • Psychiatrists • Support Staff • Pediatricians • Corrections Officers “The quality of the staff-patient interaction and attitudes of staff, good management of clinics and quality of record keeping are factors which have been linked to outcomes of treatment.” Bell 2000

40. Interdisciplinary Program Orange County Jail Winnie Palmer Hospital Maternity and Neonatal Care Opiate Treatment Program (CFDFL) Methadone Dosing Counseling Psychiatric Care Detox/ARF CFDFL PPWI/CFDFL Residential Treatment

41. Opioid Agonist Maintenance in Pregnancy • Methadone is the only medication currently recognized for the treatment of opioid addiction in pregnancy (US). • Maintenance with methadone during pregnancy produces the same benefits as treatment in the non-pregnant patient. • A pregnant patient CAN taper off of methadone (opioid agonist therapy) but should not be permitted to experience significant abstinence syndrome. • Luty, J, Nilolaou V, Bearn J. 2004 • But, medically supervised withdrawal is not the standard of care due to the poor outcomes (Jones H, 2008) and the potential catastrophic consequences of relapse. • Because the goal of treatment with methadone is to prevent relapse to illicit substance use.

42. Pregnant Patients Receive All the Same Benefits as Non-Pregnant Patients on Maintenance Therapy • Reduction in All Cause Mortality • “…the all cause mortality rate for patients receiving methadone maintenance treatment was similar to the mortality rate for the general population whereas the mortality rate of untreated individuals using heroin was more than 15 times higher.” Bell 2000

43. Pregnancy Specific Benefits of Opioid Maintenance Therapy • Methadone Maintenance Therapy (MMT) is regarded as an established treatment with birth outcomes comparable to a general obstetrical population (Kreek MJ, 2000) • Fewer Pre-term Births • Less Intrauterine Growth Restriction • Fewer Low Birth Weight • Less Maternal Drug Use • Greater reduction with adequate dose of methadone • Improved Prenatal Care Compliance Burns L, 2004; Goler NC, 2008 • There appears “to be no differential effect of either treatment (methadone or buprenorphine)—it was exposure to stable treatment that was important. • Gibson 2008

44. Principles of Opioid Agonist Therapy • Opioids bind the mu opioid receptors in the brain. • The mu receptor generates the effects experienced by the patient/drug user. • Different opioids stimulate the receptor to a greater or lesser degree. • By occupying the mu receptor with a long acting opioid the effects of other opioids are impeded or attenuated. • By dosing regularly and before developing symptoms of abstinence syndrome the mu receptors will be occupied when a trigger or craving is experienced. • A higher dose occupies more receptors longer.

45. Methadone Maintenance Treatment(MMT) in Perinatal Addiction • MMT is but a single element in the variety of services needed for optimal care of the pregnant opioid dependent patient. • Comprehensive MMT with adequate prenatal care can reduce the incidence of obstetrical and fetal complications, intrauterine growth retardation, and neonatal morbidity and mortality (Finnegan, 1991)

46. Principles of Pharmacotherapy with Methadone • Methadone is the only agonist therapy recognized for use in pregnancy. It is supported by 30 years of research. • Category C, but recognized by NIH consensus panel for the use in pregnancy. • Methadone is a full agonist so the effect is directly proportionate to the dose. • It takes 24 to 36 hours for the body of a healthy person to eliminate half of the methadone ingested. • A person with impaired liver function or on other medications/intoxicants may require up to 50 hours to eliminate half of the methadone. • The opioid “blocker” effect is a result of having the mu opioid receptor occupied with methadone when another opioid is introduced.

47. Safe and Effective Induction with Methadone: Outpatient • Safe dose: • “Start low and go slow.” It takes 5 days to reach steady state. • Respiratory depression develops later than peak effect. • Cross tolerance between opioids is not 100% • Average dose: • 80 to 120mg • Titrate to effect/individualize treatment • Effective dose: • Abolishes abstinence syndrome for at least 24 hours. • Does not cause over–sedation at peak effect (4 hours after dosing.) • Methadone and buprenorphine are potent opiates, they are not to be used in the opiate naive patient.

48. Methadone Induction

49. Getting the Prenatal Dose Right: Induction and Stabilization

50. Principles of Pharmacotherapy with Buprenorphine (Subutex) • Antagonist / High receptor affinity • Highest receptor affinity and receptor occupancy: 95% occupancy at 16 mg (Greenwald et al, 2003) • Blockade or attenuate effect of other opioids • Rapid onset of action and risk of acute opioid reversal • Partial receptor agonist / Low Intrinsic Activity • Lower physical dependence • Limited development of tolerance • Ceiling effect on respiratory depression • Long Acting / Slow dissociation from receptor • Long duration of action • Milder withdrawal • t ½ - 24 – 36 hrs • Fentanyl and hydromorphone – also have high affinity for receptor