Follow-up Q and A Webinar with Case Discussions: A Review of Opioids and

Treatment of Opioid Dependence

Joji Suzuki, MD Director, Division of Addiction Psychiatry

Department of Psychiatry, Brigham and Women’s Hospital Assistant Professor of Psychiatry, Harvard Medical School

• I have no relevant disclosures to report

Joji Suzuki, Disclosures

Planning Committee, Disclosures

AAAP aims to provide educational information that is balanced, independent, objective and free of bias and based on evidence. In order to resolve any identified Conflicts of Interest, disclosure information from all planners, faculty and anyone in the position to control content is provided during the planning process to ensure resolution of any identified conflicts. This disclosure information is listed below:

The following developers and planning committee members have reported that they have no commercial relationships relevant to the content of this webinar to disclose: AAAP CME/CPD Committee Members Dean Krahn, MD, Kevin Sevarino, MD, PhD, Tim Fong, MD, Tom Kosten, MD, Joji Suzuki, MD; and AAAP Staff Kathryn Cates-Wessel, Miriam Giles, Sharon Joubert Frezza, and Justina Andonian.

All faculty have been advised that any recommendations involving clinical medicine must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in the presentation must conform to the generally accepted standards of experimental design, data collection, and analysis. Speakers must inform the learners if their presentation will include discussion of unlabeled/investigational use of commercial products.

Target Audience

• The overarching goal of PCSS-O is to offer evidence-based trainings on the safe and effective prescribing of opioid medications in the treatment of pain and/or opioid addiction.

• Our focus is to reach providers and/or providers-in-training from diverse healthcare professions including physicians, nurses, dentists, physician assistants, pharmacists, and program administrators.

Educational Objectives

• Describe the epidemiology and neurobiology of opioid use disorders

• Identify the pharmacotherapy options for the treatment of opioid use disorders

• Explain the basic principles of managing opioid use disorders

Opioid Receptor Activity Receptor Activity

Mu Analgesia, Euphoria, Miosis Sedation, Constipation, Respiratory Depression, Hormonal changes, Cough suppresion, nausea

Kappa Analgesia, Diuresis, Sedation, Dysphoria, Hallucinations, Respiratory Depression

Delta Analgesia, Convulsant

• Opiates • Morphine • Codeine

• Semi-synthetic

• Heroin • Oxycodone • Hydrocodone • Hydromorphone • Buprenorphine • Naltrexone

• Synthetic • Methadone • Fentanyl • Tramadol • Meperidine • Propoxyphene

• Endorphins • Mitragynine • Salvinorin A

0

10

20

30

40

50

60

70

80

90

100

Nodrug

Lowdose

Highdose

Full Agonist

Antagonist

Opioid Overdose

• In setting of benzodiazepine or alcohol (majority of fatal overdoses)

• Respiratory depression (usual cause of death) • Hypotension, pinpoint pupils (may dilate with

hypoxia) • Noncardiogenic pulmonary edema • High-dose meperidine (Demerol) or

propoxyphene (Darvon) can cause seizures

DAWN (ED visits 2009)

397,160

213,118

175,949

104,490

22,143

12,544

Opioid pain relievers

Heroin

Oxycodone/combo

Hydrocodone/combo

Fentanyl/combo

Buprenorphine

<1 1-4 5-9 10-14 15-24 25-34 35-44 45-54 55-64 65+ Total

1

2

3

4

5

6

7

Top leading causes of death by age group (2012)

Accidental deaths

Suicides

Homicides

0

5

10

15

20

2519

80

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

Dea

ths

per 1

00,0

0 Poisonoing deaths leading cause of accidental death, 90% from drug induced overdoses

Motor vehicle accidentPoisoningDrug induced overdoses

T: Tolerance: Needing more to get the same effect W: Withdrawal: Withdrawal when stop or reduce A: Using larger Amounts than intended C: Persistent desire or failed attempts to Cut down K: Use despite Knowledge of harm S: Spend a lot of time obtaining/using/recovering S: Social obligations are given up due to drug use

Opioid Dependence (“Addiction”)

• 0.1-0.2 mg PO TID • Hold if SBP<90 Clonidine

• 20-40mg PO Daily, then taper over the course of several days Methadone

• 8-16mg SL Daily, then taper over the course of several days Buprenorphine

Formulation Brand Name Dosages

Sublingual

Suboxone: Buprenorphine + Naloxone

Subutex: Buprenorphine Only

8/2 or 2/0.5mg

8 or 2mg

Parenteral

Buprenex

300mcg/ml

Transdermal

Butrans

5, 10, 20mcg/hr

Implant

Probuphine

Still in research

The sublingual formulations are the only ones approved for the treatment of opioid dependence

Buprenorphine Partial agonist Office-based prescribing Can be diverted Potential for precipitated withdrawal Low overdose risk Able to block other opioids Minimal drug-drug interactions, except benzodiazepines Can complicate pain treatment

Methadone

Full agonist Only through methadone clinics Cannot be diverted (easily) Cardiac toxicities High overdose risk Can block other opioids at higher doses Known drug-drug interactions

Questions from Previous Webinar

1) Are you aware of any new developments at FDA as to naltrexone implants? 2) You said the buprenorphine diversion is a huge problem but doesn’t research show

that this results largely because people addicted to opioids are seeking bupe to stop using?

3) Can one poppy bagel or all thing bagel give positive urine? 4) The studies you shared are very compelling. I live in a part of the country with very

limited access to MAT in part because of the policies of our community mental health center. What advise do you have for encouraging our system to reconsider their policies?

5) What is your response with administering methadone maintenance with a MD prescribing benzodiazepines?

6) Recommendations for using buprenorphine with adolescents? 7) Is it possible to override withdrawal precipitated by BUP admin with additional

BUP? 8) Should every patient on long-term opioid therapy also be on at least one adjunctive

medication? 9) Some comments on the use of glutamate pathway drugs. Which one do you prefer?

John is a 50 year old divorced male with a history of hypertenstion, diabetes, and an extensive history of opioid, cocaine, and sedative/hypnotic use disorder. John describes his initial exposure to prescription opioids 25 years ago following a car accident, which quickly escalated to illicit oxycodone and morphine, and eventually IV heroin. He is currently homeless, unemployed, and has limited social supports. In the past year, he has had several detox admissions and is frequently lost to follow up. He had two unintentional overdoses in the past due to illicit opioid and benzodiazepine use. Today, he presents to his primary care doctor to consider potential treatments. He admits he never thought he needed ongoing treatment, but feels it is time for him to become serious about it. John is not on any prescribed medications. Laboratory evaluation including LFTs and kidney function are within normal limits. EKG shows NSR and normal QTc of 420 ms. Urine toxicology is positive for opiates, cocaine, and benzodiazepines. PMP does not reveal any other active prescriptions for controlled substances. John notes that he has several upcoming appointments with dental care as he has had poor dental health related to his use and has multiple procedures lined up for this purpose. Exam is notable for slightly disheveled appearance and 2 mm pupils. What are the treatment options for John?

Case 1

Samantha is a 23 year olf female with a history of depression and opioid use disorder. She begn using opioids following the birth of her first daughter two years ago, but never quite stopped taking the oxycodone. She began escalating her use, now using about 80mg a day intranasally, and her credit card is maxed out to support her habit. She does not use IV, and does not use alcohol or other substances. She has been able to keep her job as a receptionist in a doctor’s office despite her ongoing use, but acknowledges she cannot continue doing this much longer. Her depression is getting worse in the context of the stress of being a single-mom, and trying to keep her opioid use under control. Samantha tried “cold turkey” several times, but the withdrawals were too much to bear, and she relapsed immediately. She then tried a detox admission, but relapsed within 1 week of discharge due to strong cravings. She expresses interest in buprenorphine treatment, noting that her friend offered her a few tablets several weeks ago, which completely took away the withdrawal and cravings for several days. She reports a desire to “do this right for my daughter” and wanted professional treatment. Her labs are significant for urine toxicology that is positive only for opiates. beta-Hcg is negative. PMP reveals no prescriptions for controlled substances. Exam is without significant findings. What are the treatment options for Samantha?

Case 2

Tim is a 27 year old male graduate student with a history of opioid use disorder currently stable on buprenorphine. He started using prescription opioids illicitly after trying it a party 3 years ago, but quickly escalated to using Oxycontins 120mg a day, mostly by mouth but increasingly intranasally. His brother was also using the pills, at the time, but when he overdosed 2 years ago, he sought out treatment. He started treatment with buprenorphine, and has not used any illicit opioids for almost 2 years. He has aspirations of becoming a health care professional, but feels staying on an agonist is not an option. As such, he is asking to be tapered off completely from his current dose of 16mg a day. He heard about naltrexone, and wonders if that is a viable option for him. He is on no other medications, labs are unremarkable. He attends AA/NA regularly, has good supports at home, and has an addiction therapist he sees regularly. What are the treatment options for Tim?

Case 3

www.pcssmat.org www.asam.org

www.aaap.org

References • American Psychiatric Association: Diagnostic and Statistical Manual of Mental

Disorders, Fourth Edition, Text Revision, Washington DC, American Psychiatric Association, 2000.

• Drug Abuse Warning Network, National Estimate, 2009

• Greenwald M, Johanson CE, Bueller J, et al: Buprenorphine duration of action: mu-opioid receptor availability and pharmacokinetic and behavioral indices. Biol Psychiatry. 61(1):101-10. 2007.

• Johnston L, O'Malley P, BachmanJ, & Schulenberg J Monitoring the Future national survey results on drug use, 1975-2009. Volume I: Secondary school students (NIH Publication No. 10-7584). Bethesda, MD: National Institute on Drug Abuse. 2010.

• Jones H, Kaltenbach K, Heil S, et al.: Neonatal abstinence syndrome after methadone or buprenorphine exposure. NEJM. 363 (24):2320-2331, 2010.

• Kakko J, Heilig M, Ihsan S: Buprenorphine and methadone treatment of opiate dependence during pregnancy: comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug and Alcohol Dependence 96: 69-78, 2008

• Kakko J, Svanborg KD, Kreek MJ, Heilig M: 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet. 361(9358):662-8. 2003.

• Kerr D, Kelly A, Dietze P, Jolley D, Barger B: Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose. Addiction. 104(12):2067-74. 2009.

• Ling W, Hillhouse M, Domier C, et al.: Buprenorphine tapering schedule and illicit opioid use. Addiction 104: 256-265, 2009.

References

References • McCance-Katz EF, Sullivan LS, Nallani S: Drug interactions of clinical importance

between the opioids, methadone and buprenorphine, and frequently prescribed medications: A review. Am J Addictions, 19: 4–16, 2010.

• Mégarbane B, Buisine A, Jacobs F, et al: Prospective comparative assessment of buprenorphine overdose with heroin and methadone: clinical characteristics and response to antidotal treatment. J Subst Abuse Treat. 38(4):403-7. 2010 Epub 2010 Feb 26.

• National Survey on Drug Use and Health, SAMHSA, Rockville, MD. 2010.

• Scherbaum N, Klein S, Kaube H, Kienbaum P, Peters J, Gastpar M: Alternative strategies of opiate detoxification: evaluation of the so-called ultra-rapid detoxification. Pharmacopsychiatry. 31(6):205-9. 1998.

• Woody G, Poole S, Subamaniam G, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA. 300(17):2003-2011.

• http://www.cdc.gov/HomeandRecreationalSafety/pdf/poision-issue-brief.pdf

References

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: pcss-o@aaap.org.

For more information on requesting or becoming a mentor visit: pcss-o.org/colleague-support

PCSS-O is a collaborative effort led by American Academy of Addiction Psychiatry (AAAP) in partnership with: 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),and International Nurses Society on Addictions (IntNSA).

For more information visit: www.pcss-o.org

For questions email: pcss-o@aaap.org

Twitter: @PCSSProjects

Funding for this initiative was made possible (in part) by Providers’ Clinical Support System for Opioid Therapies (grant no. 5H79TI023439) 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.