pcss-o christensen powerpoint · 97$ wkh ³jdv wdqn´ vxssolhv grsdplqh wr wkh 1xfohxv $ffxpehqv...

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Pregnancy and Addiction

Carl Christensen, MD, PhD, D-FASAMClinical Associate Professor, OB Gyn & Psychiatry

Wayne State University School of MedicineNovember 16, 2016

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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.

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WHY TALK ABOUT THIS?

Addiction and Pregnancy 3

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WHY TALK ABOUT THIS?


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WHY TALK ABOUT THIS?N.A.S. in Southeastern Mich


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What is Addiction?

Physiology of Addiction 6

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The Nucleus Accumbens: Craving and Reward


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VTA: the “gas tank”: supplies dopamine to the Nucleus Accumbens


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Frontal Cortex: Impulse Control


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What is Addiction?

• Addiction is not a problem of drug WITHDRAWAL…..

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What is Addiction?

• It is a problem of:

oCRAVING

oLOSS OF CONTROL

oCOMPULSIVE USE

oUSE DESPITE CONSEQUENCES

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12Physiology of Addiction 12

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Frontal Cortex and Addiction


High flow

Low flow

Healthy Control Cocaine-dependent

Gottschalk, 2001, Am J Psychiatry

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Non users

Cocaine users, 10 days sober

Cocaine Users, 100 days sober

High blood flow

Low blood flow

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Non users



High blood flow

Low blood flow

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Non users



High blood flow

Low blood flow

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How Longto recover

fromMethamphetamine?

[C-11]d-threo-methylphenidate

Volkow et al., J. Neuroscience, 2001.

low

high

Normal Control

Methamphetamine Abuser(1 month abstinent)

Methamphetamine Abuser (14 months abstinent)

CONTROL

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30 days abstinent



low

high

Normal Control



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14 months + to recover

fromMethamphetamine!!!



low

high

Normal Control



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Treatment of Opioid Use DisorderMedication Assisted Treatment

(MAT)• Agonists

• Antagonists*

• Level I: outpatient treatment +/- MAT

• * Not currently used in Pregnancy

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Agonists vs. Antagonists

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Drug Type AnalogyMethadone Full Agonist High Octane

Buprenorphine Partial Agonist Low Octane

Naltrexone Antagonist Water

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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.


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Benefits of MethadoneSalsitz, ASAM, 2012

• Reduction in death rates (Grondblah, 1990)

• Reduction in IVDU (Ball & Ross, 1991)

• Reduction in # of crime days (Ball & Ross)

• Reduced HIV seroconversion / HCVconversion

• IMPROVED OUTCOME AFTER INCARCERATION

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Ball 1988: reduction in IVDU

ORT: yes or no??? 27

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Ball 1988: reduction in IVDU


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Ball 1988: resumption of IVDU!


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Ball 1988: resumption of IVDU!


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Buprenorphine

A partial opiate agonist (less potent)

◦ Less analgesic effect◦ Less respiratory depression◦

32Addiction and Pregnancy 32

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


Buprenorphine

• Formulations approved for PAIN: Buprenex®: parenteral, used in the hospital setting. Butrans®: weekly patch, 10 to 20 mcg/hr Belbuca®: buccal film from 75 – 900 mcg/24 hr.

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What Formulation Should You Use?

• Generic buprenorphine avoids naloxone.

• It is more susceptible to diversion

• Use whatever their insurance will pay for!!

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Buprenorphine long-term follow up: Fiellin, 2008

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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)

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Vivitrol® (injectable naltrexone) for opioid dependence

This medication is not currently used during pregnancy; but may be used following

delivery.

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Addiction Tx in Russia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160743/

Kupitsky et al; Lancet 2011; 377: 1506-13

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Vivitrol: abstinence

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Vivitrol: craving

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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.

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Can you detox?

Doc, when can I get off this sh*tmedication?

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Luty 2003

• 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


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Detoxing During Pregnancy? Luty 2003Luty 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


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Maintenance vs. Detox? Kakko et al 2003

• 40 heroin addicts were started on buprenorphine/naloxone.

• 20 were “detoxed” off and offered counseling.• 20 were kept on buprenorphine and offered

counseling.• A year later…….


4646 ORT: ye

4747 ORT: ye

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Can you taper off buprenorphine without relapse?

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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.

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Opioid Detox During PregnancyBell 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%)

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Treatment of Opioid Dependence During Pregnancy

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METHADONE“the gold standard”

• Was only approved for use for addiction in 1965; Dr. James Wardell started in Detroit in 1969.

• 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.

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Maternal Opioid Treatment:Human Experimental Research

(MOTHER)


:NEJM 2010; 363: 2320-31


MOTHER STUDY

• Double blinded, RCT

• Methadone vs. buprenorphine

• Contingency management (financial incentives $$$$)

• CBT (cognitive behavioral tx)

• Transportation, etc.

• NO polysubstance dependence x tobacco!


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


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

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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


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Dropped out 18% 33


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Dropped out 18% 33


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Dropped out 18% 33


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Dropped out 18% 33


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Dropped out 18% 33


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Dropped out 18% 33


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Dropped out 18% 33


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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

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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


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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


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Buprenorphine-->Methadone?

• NOT necessary!

• Can continue buprenorphine

• Risk of NAS is decreased (severity and duration)


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Methadone 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.


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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.

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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

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Epidural Management

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Middle East J Anesthesiol 2013 Oct; 22(3): 273-81


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!!






tells you!!



• 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


tells you!!






tells you!!

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Developed for Families Against Narcotics

http://www.familiesagainstnarcotics.org/

The Opioid Epidemic& Naloxone (Narcan®) Rescue

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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)

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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.

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Naloxone formulations:

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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

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OD deaths: heroin and Fentanyl: Washtenaw Co.

28 (heroin) 21 (fentanyl + heroin)12 (pills) (25%)

49 (total)

75% DUE TO HEROIN +/- FENTANYL; 25% DUE TO PRESCRIPTION PILLS

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Fentanyl on Urine Drug ScreenPregnant Patient

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How To Do A Naloxone Rescue(youtube.com -> ccmdphd)

• Make Sure They are Not Breathing

• (always) Call 911

• Do Rescue Breaths (not compressions)

• Give Naloxone

• Resume Rescue Breaths

• Repeat Naloxone every 3 mins

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Olive: non narcotic therapy dog

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Contact InformationCarl Christensen

• www.christensenrecovery.com

• [email protected]

• Voice mail 734 448 0226

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PCSS-O Colleague Support Program and Listserv

• PCSS-O Colleague Support Program is designed to offer general information to health professionals seeking guidance in their clinical practice in prescribing opioid medications.

• PCSS-O Mentors comprise a national network of trained providers with expertise in addiction medicine/psychiatry and pain management.

• Our mentoring approach allows every mentor/mentee relationship to be unique and catered to the specific needs of both parties.

• The mentoring program is available at no cost to providers.

• Listserv: A resource that provides an “Expert of the Month” who will answer questions about educational content that has been presented through PCSS-O project. To join email: [email protected].

For more information on requesting or becoming a mentor visit:

www.pcss-o.org/colleague-support

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PCSS-O is a collaborative effort led by American Academy of Addiction Psychiatry (AAAP) in partnership with: Addiction Technology Transfer Center (ATTC), American Academy of Neurology (AAN), American

Academy of Pain Medicine (AAPM), American Academy of Pediatrics (AAP), American College of Physicians (ACP), American Dental Association (ADA), American Medical Association (AMA), American

Osteopathic Academy of Addiction Medicine (AOAAM), American Psychiatric Association (APA), American Society for Pain Management Nursing (ASPMN), International Nurses Society on Addictions (IntNSA), and

Southeast Consortium for Substance Abuse Training (SECSAT).

For more information visit: www.pcss-o.orgFor questions email: [email protected]

Twitter: @PCSSProjects

Funding for this initiative was made possible (in part) by Providers’ Clinical Support System for Opioid Therapies (grant no. 5H79TI025595) from SAMHSA. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department

of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

pcss-o christensen powerpoint · 97$ wkh ³jdv wdqn´ vxssolhv grsdplqh wr wkh 1xfohxv $ffxpehqv...

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