Disclosures. Objectives 10/2/2017. OHIO ASSOCIATION OF ADVANCED PRACTICE NURSES Drugs of Addiction: Alcohol and Opioid Pharmacotherapy

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1 OHIO ASSOCIATION OF ADVANCED PRACTICE NURSES Drugs of Addiction: Alcohol and Opioid Pharmacotherapy Sara Dugan, PharmD, BCPP, BCPS Associate Professor, Pharmacy Practice Associate Professor, Psychiatry Northeast Ohio Medical University Chris Paxos, PharmD, BCPP, BCPS, CGP Pharmacotherapy Specialist, Psychiatry Cleveland Clinic Akron General Disclosures Sara Dugan has no actual or potential conflict of interest in relation to this presentation. Chris Paxos has no actual or potential conflict of interest in relation to this presentation. Objectives 1. Describe various rating scales used for the screening or assessment of substance use disorders 2. Compare medications used for maintenance treatment of alcohol use disorder 3. Compare medications used for maintenance treatment of opioid use disorder 4. Discuss medication related pearls for treating patients with substance use disorders 1

2 Substance Use Disorders Ohio Association of Advanced Practice Nurses Assessment Question #1 Which of the following criteria for substance use disorders was present in DSM IV TR but was removed as a criterion in DSM 5? A. Recurrent use in hazardous situations B. Taking for longer than intended C. Recurrent legal problems D. Desire to cut down on use Substance Use Disorders Problematic pattern of substance use with clinically significant distress or impairment with 2 of the following within a 12 month period: 1. Taking in larger amounts or for longer than intended 2. Wanting to cut down on use or quit but not being able to do it 3. Significant time spent obtaining, using, or recovering from use 4. Craving or strong desire to use 5. Recurrent use with significant impact on school, work, or home obligations 6. Continued use despite social and interpersonal problems 7. Giving up social, occupational, or recreational activities 8. Recurrent use in physically hazardous situations 9. Continued use despite knowledge of persistent or recurrent physical or psychological difficulties from use 10. Tolerance 11. Withdrawal Diagnostic and Statistical Manual of Mental Disorders,

3 Dependence and Tolerance Dependence Adaptive physiological state that occurs with regular drug use and results in a withdrawal syndrome when drug use is stopped Tolerance Condition in which higher doses of a drug are required to produce the same effect achieved during initial use Image from: by grayson haines/2 tolerance withdrawal. NIDA Research Report Series, Addiction Chronic, relapsing disease characterized by compulsive drug seeking and use, despite serious adverse consequences, and by long lasting changes in the brain Often includes dependence Addiction is likely a result of a person s environment, genetics, and the pharmacologic characteristics of the drug Pharmacologic characteristics that increase the likelihood addiction Lipophilicity, administration route, activity resulting in reward and reinforcement Oral Snorted Smoked Injected Speed of entry to the brain NIDA Research Report Series, J Addict Dis. 2012;31(3): Gabapentin and OARRS Ohio Association of Advanced Practice Nurses 3

4 Gabapentin Ohio Automated Rx Reporting System (OARRS) Gabapentin added to OARRS in December 2016 Not scheduled as a controlled substance in the state of Ohio Not required to check OARRS prior to prescribing Gabapentin misuse Nearly 57 million prescriptions in 2015, a 42% increase from 2011 Described as producing euphoria, marijuana like high, or zombie like effects Commonly used with opioids, muscle relaxants, and anxiolytic medications Kentucky survey showed 15% used it to get high in past 6 months Removed from various correctional facilities Reports of use as a cutting agent in heroin Am J Psychiatry. 2015;172(5): Available at: pharmacy.ohio.gov/gabapentin. Available at: pharmacytimes.com. Rating Scales Ohio Association of Advanced Practice Nurses Psychiatric Measures Clinical Opiate Withdrawal Scale (COWS) Handbook of Psychiatric Measures,

5 Psychiatric Measures CAGE Questionnaire Handbook of Psychiatric Measures, Psychiatric Measures Alcohol Use Disorders Identification Test (AUDIT) 10 item questionnaire Handbook of Psychiatric Measures, Psychiatric Measures Alcohol Use Disorders Identification Test (AUDIT) 3 item questionnaire Handbook of Psychiatric Measures,

6 Psychiatric Measures Single question screening U.S. Preventive Services Task Force How many times in the past year have you had five (for men) or four (for women and all adults older than 65 years) or more drinks per day? Am Fam Physician. 2016;93(6): Alcohol Use Disorder Pharmacotherapy Ohio Association of Advanced Practice Nurses Psychopharmacology Trivia The pharmacologic effects of which medication were first observed in workers in the vulcanized rubber industry? 6

7 Pharmacotherapy Three medications are FDA approved for alcohol use disorder Most patients diagnosed with AUD are not prescribed AUD medications Disulfiram Antabuse 1994 Naltrexone ReVia 2004 Acamprosate Campral 2006 Naltrexone Vivitrol JAMA. 2017;317(22): Assessment Question #2 All of the following medications for the treatment of alcohol use disorder require periodic liver function monitoring due to the risk of hepatotoxicity, EXCEPT: A. Acamprosate (Campral ) B. Disulfiram (Antabuse ) C. Naltrexone (ReVia ) D. Naltrexone (Vivitrol ) Assessment Question #3 Which of the following alcohol use disorder medications does NOT pharmacologically lessen cravings for alcohol? A. Acamprosate (Campral ) B. Disulfiram (Antabuse ) C. Naltrexone (ReVia ) D. Naltrexone (Vivitrol ) 7

8 Disulfiram (Antabuse ) Mechanism of action Inhibits aldehyde dehydrogenase (ALDH) Results in acetaldehyde accumulation Aversive therapy to deter drinking Disulfiram reaction flushing palpitations sweating anxiety nausea, vomiting shortness of breath tachycardia BP dizziness Am Fam Physician. 2016;93(6): American Psychiatric Association, Disulfiram (Antabuse ) Contraindications Thiuram hypersensitivity Ethanol use Metronidazole use Severe myocardial disease Psychosis Warnings/adverse effects Hepatotoxicity Peripheral neuropathy Garlic or metallic after taste Dosing No alcohol for hours Up to 500 mg once daily for 1 2 weeks 250 mg once daily ( mg/day) Monitoring Therapeutic efficacy Periodic liver function tests Drug interactions Alcohol (contraindicated) Metronidazole (contraindicated) Am Fam Physician. 2016;93(6): American Psychiatric Association, Disulfiram (Antabuse ) Few well controlled trials; large (N=605) VA study failed to show significant difference in abstinence between disulfiram and placebo Patients Remaining Abstinent (%) Nonadherent (80%) Adherent (20%) Disulfiram 250mg (n=202) Disulfiram 1mg (n=204) Placebo (n=199) JAMA. 1986;256(11):

9 Acamprosate (Campral ) Mechanism of action NMDA receptor antagonist GABA/glutamate balance May reduce alcohol cravings Dosing 666 mg three times daily CrCl ml/min: 333 mg three times daily Contraindications CrCl < 30 ml/min Warnings/adverse effects Depression, suicidal ideation Diarrhea (10 17%) Monitoring Therapeutic efficacy Periodic renal function tests Mental status Other considerations No known interactions No hepatic metabolism Am Fam Physician. 2016;93(6): American Psychiatric Association, Campral prescribing information. Naltrexone (ReVia ) Mechanism of action Mu opioid receptor antagonist May reduce alcohol cravings Contraindications Opioid within 7 10 days Acute opioid withdrawal Positive opioid urine screen Failing naloxone challenge Warnings/adverse effects Dose related hepatic injury Nausea, headache, insomnia Dosing 50 mg once daily 100 mg every other day 150 mg every 3 days Monitoring Therapeutic efficacy Periodic liver function tests Drug interactions Opioid receptor agonists Peripheral opioid antagonists Naltrexone polypharmacy Am Fam Physician. 2016;93(6): American Psychiatric Association, ReVia prescribing information. Naltrexone (ReVia ) +? Predictors of naltrexone responsive patients with alcohol use disorder Alcohol use disorder family history OPRM1 gene polymorphism (Asp40) High pretreatment craving Male sex Pretreatment drinking 2 0 Addiction. 2014;109(8):

10 Naltrexone IM (Vivitrol ) Contraindications Opioid use within 7 10 days Acute opioid withdrawal Positive opioid urine screen Failing naloxone challenge Dosing and administration 380 mg IM every 4 weeks Gluteal, alternating buttocks Injection site reactions ( 65%) Bruising, pain, abscess, necrosis Vivitrol prescribing information. Naltrexone IM (Vivitrol ) REMS counseling points 1) Risk of opioid overdose 2) Severe injection site reactions 3) Precipitation of opioid withdrawal 4) Diminished effects of opioids 5) Hepatotoxicity REMS website Patient counseling tools Required medication guide Wallet card, medical bracelet Available at: vivitrolrems.com. Patient Education Disulfiram Carry wallet card or use medical bracelet Avoid alcohol and alcohol containing products Disulfiram reaction may occur up to 14 days after stopping Adherence (e.g., supervised, group support) enhances effectiveness Naltrexone Carry wallet card or use medical bracelet Signs and symptoms of hepatotoxicity Avoid use of opioid medications Educate on REMS program requirements Acamprosate Medication adherence counseling Avoid doubling up on doses Am Fam Physician. 2016;93(6): American Psychiatric Association,

11 Mini Case Study #1 Harold arrives for his appointment at the clinic. He is diagnosed with alcohol use disorder (AUD) and has been abstinent for 2 months. He is currently treated with CBT and regularly attends AA meetings. Labs, including LFTs, are within normal limits. His CrCl is 45 ml/min. He takes duloxetine for MDD. During the appointment, medications for AUD are discussed, and Harold is agreeable to trying something to reduce cravings but admits he frequently misses doses of medications. Which of the following would be the most appropriate option? A. Acamprosate B. Disulfiram C. Lorazepam D. Naltrexone Treatment Guidelines General approach to pharmacotherapy There is no universally accepted medication algorithm Medication selection should be based on patient characteristics Combine with concurrent psychosocial treatment First line Secondline British Association for Psychopharmacology (2012) Acamprosate Naltrexone World Federation of Societies of Biological Psychiatry (2008) Acamprosate Naltrexone Disulfiram Disulfiram American Psychiatric Association (2006) Acamprosate Naltrexone Disulfiram J Psychopharmacol. 2012;26(7): World J Biol Psychiatry. 2008;9(1):6 23. American Psychiatric Association, Treatment Decision Grid Acamprosate Disulfiram Naltrexone IM Naltrexone Renal failure X A A A Significant liver disease A C C C Coronaryartery disease A C A A Chronic pain A A C C Current opioid use A A X X Psychosis A C A A Unable to remain abstinent A X A A Poor adherence risk factors C C C A Obesity that precludes IM A A A X Family history of AUD A A A A High level of craving A A A A Cognitive impairment A X A A A=appropriate to use; C=use with caution; X=contraindicated SAMHSA,

12 Assessment Question #4 According to the COMBINE trial, which treatment option yields the highest rate of abstinence for a patient diagnosed with alcohol use disorder? A. Acamprosate + Medical Management B. Naltrexone + Medical Management C. Acamprosate + Behavioral Intervention D. Naltrexone + Behavioral Intervention Landmark Study: COMBINE Objective Evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence Study design Medical management (MM) (n = 607) Placebo Acamprosate Placebo Naltrexone MM + combined behavioral intervention (n = 619) Placebo Acamprosate No Pills Placebo Naltrexone No Pills 157 JAMA. 2006;295(17): Landmark Study: COMBINE Primary outcomes Percent of days abstinent from alcohol Time to first heavy drinking day Results All groups showed reductions in drinking Naltrexone + MM had highest percentage (80.6%) of days abstinent Acamprosate demonstrated no greater efficacy than placebo Combining acamprosate + naltrexone did not increase efficacy Limitation Doses higher than what is generally prescribed Naltrexone 100 mg vs. 50 mg; acamprosate 3,000 mg vs. 2,000 mg JAMA. 2006;295(17):

13 Acamprosate vs. Naltrexone Meta analysis (N=122 trials) Both acamprosate and naltrexone reduced return to drinking When compared, no significant differences were found Other factors (e.g., adverse effects) to guide treatment Meta analysis (N=64 trials) Acamprosate may be more effective at maintaining abstinence Naltrexone may more effectively reduce heavy drinking and craving Detoxification or a longer period of abstinence were associated with greater treatment effects for acamprosate and naltrexone, respectively JAMA 2014;311(18): Addiction. 2013;108(2): Mini Case Study #2 A 67 year old combat veteran with alcohol use disorder (AUD), posttraumatic stress disorder, and end stage renal disease (ESRD) is discharged from the hospital after a 5 day detoxification from alcohol. The patient failed a previous trial of long acting naltrexone for AUD, and his ESRD precludes the prescribing of acamprosate therapy. While discussing treatment options, the patient mentions he does not want the medication that makes people feel sick. Which of the following medications would be a potential (off label) option? A. Aripiprazole B. Levetiracetam C. Methadone D. Topiramate Emerging Therapies Several off label medications have been investigated topiramate (Topamax ) zonisamide (Zonegran ) gabapentin (Neurontin ) baclofen (Lioresal ) ondansetron (Zofran ) aripiprazole (Abilify ) JAMA. 2007;298(14): Lancet. 2003;361(9370): Psychopharmacology. 2002;160(4): J Clin Psychopharmacol. 2008;28(1):5 12. Lancet. 2007;370(9603): Am J Drug Alcohol Abuse. 2007;33(3): JAMA Intern Med. 2014;174(1):70 7. J Clin Psychopharmacol. 2010;30(3): Alcohol Clin Expo Res. 2010;34(11):

14 Summary Three medications are FDA approved for the maintenance treatment of alcohol use disorder: acamprosate, disulfiram, and naltrexone Acamprosate and naltrexone work to reduce cravings and promote abstinence, whereas disulfiram deters drinking by producing an aversive reaction to alcohol to promote abstinence Guidelines recommend acamprosate or naltrexone as first line medications and generally distinguish between the two on the basis of pharmacologic properties Several medications have been or are currently being studied for the maintenance treatment of alcohol use disorder Opioid Use Disorder (OUD) Pharmacotherapy Ohio Association of Advanced Practice Nurses Where it began Images from: pictures.picphotos.net/immigrants arriving at ellis island 1903/

15 Approach to OUD Treatment Opioid addiction is a medical disorder that can be treated effectively with medications when they are administered under conditions consistent with their pharmacological efficacy and when treatment includes necessary supportive services such as psychosocial counseling, treatment for cooccurring disorders, medical services, and vocational rehabilitation SAMHSA, Focus on Maintenance Therapy Abstinence Maintenance Intoxication Detoxification Withdrawal Opioid Withdrawal Anxiety Restlessness Rhinorrhea Lacrimation Pupillary dilation Nausea Vomiting Diarrhea Abdominal cramps Insomnia Image from Diagnostic and Statistical Manual of Mental Disorders,

16 Focus on Maintenance Therapy Abstinence Maintenance Intoxication Detoxification Withdrawal Usage vs. Number in Treatment Past Year Usage Rates Ages 12 and Up Patients Enrolled in Treatment United States Male Female Past Illicit Drug Use Past Heroin Use Past Prescription Drug Use # in Methadone Tx Programs # in Buprenorphine Tx Programs SAMHSA, Medication Assisted Treatment (MAT) Methadone (Dolophine ) Detoxification treatment of opioid addiction Maintenance treatment of opioid addiction, in conjunction with appropriate social and medical services Buprenorphine (Probuphine Implant Kit, Subutex ) Buprenorphine and Naloxone (Suboxone ) Treatment of opioid dependence Naltrexone (ReVia, Vivitrol ) Blockade of effects of exogenously administered opiates Prevention of relapse to opioid dependence Dolophine prescribing information. Buprenorphine prescribing information. Suboxone prescribing information. ReVia prescribing information. Vivitrol prescribing information. 16

17 Assessment Question #5 Which of the following medications used for medication assisted treatment of opioid dependence is least likely to cause opioid withdrawal symptoms? A. Buprenorphine (Subutex ) B. Buprenorphine/Naloxone (Suboxone ) C. Methadone (Dolophine ) D. Naltrexone (ReVia ) E. Naltrexone (Vivitrol ) Medication Assisted Treatment (MAT) Methadone (Dolophine ) Opioid receptor agonist Buprenorphine (Probuphine Implant Kit, Subutex ) Opioid receptor partial agonist Buprenorphine and Naloxone (Bunavail, Suboxone, Zubsolv ) Opioid receptor partial agonist and opioid receptor antagonist Naltrexone (ReVia, Vivitrol ) Opioid receptor antagonist Dolophine prescribing information. Buprenorphine prescribing information. Suboxone prescribing information. ReVia prescribing information. Vivitrol prescribing information. Pharmacology Definitions Agonist Activation of the receptor results in full activity Partial Agonist Activation of the receptor results in more activity than at rest but less than a full agonist Antagonist Blocks the activity of an agonist at the receptor 17

18 Selecting a Treatment Option Image from: Naltrexone (ReVia, Vivitrol ) Naltrexone (ReVia, Vivitrol ) Mechanism of action Antagonist of mu (μ) and kappa (κ) receptors Competitively binds to the receptor, blocking the actions of opiates Warnings Potential for opiate overdose after discontinuation Hepatic dysfunction Renal impairment Contraindications Hypersensitivity to naltrexone Concomitant use of opiates Acute opioid withdrawal Current physiologic opiate dependence Drug Interactions Use of opiate containing medications Pain medications Cough and cold products Anti diarrheal medications ReVia prescribing information. Vivitrol prescribing information. 18

19 Naltrexone (ReVia, Vivitrol ) Dosing Oral: Initial test dose 25 mg on day 1 50 mg once daily May use alternate day dosing 100 mg every other day 150 mg every third day Injection: 380 mg IM gluteally every 4 weeks Office based treatment Adverse Effects Injection site reactions Edema, induration, pain Anxiety Gastrointestinal effects Cramps, diarrhea, nausea Headache Syncope Monitoring Abstinence from opiates Depressive symptoms Liver function tests Suicidality ReVia prescribing information. Vivitrol prescribing information. Naltrexone Hepatotoxicity Unclear risk Report of decrease in liver function tests over 12 weeks Limited elevation in lever function test when followed up to 36 months Trial evaluated 10 patients Age range years Median treatment duration was 33 months J Clin Pharmacol. 1988;28(1): J Clin Pharmacol. 1994;34(9): Naltrexone (ReVia ) Cochrane Database of Systematic Reviews,

20 Naltrexone (ReVia ) Cochrane Database of Systematic Reviews, Naltrexone IM (Vivitrol ) Randomized, DB, PC trial for 24 weeks Patients completed 1 week of detoxification Naltrexone ER IM 380 mg q 4 weeks (n=126) Completers 57.9% (73/126) Placebo q 4 weeks (n=124) Completers 41.9% (52/124) Primary endpoint Confirmed abstinence weeks 5 24 Open label (OL) 1 year extension of Naltrexone ER IM Naltrexone ER IM group had 53.2% (67/126) enroll in OL Placebo group had 37.9% (47/124) enroll in OL 90.00% 81% 80.00% 73.70% 70.00% 66% 60.00% 53.20% 48% 49.30% 50.00% 40.00% 35.70% 30.00% 22.60% 20.00% 10.00% 0.00% Proportion of 50% opioid Proportion of Average patients with free weeks DB patients with negative urine total total drug screens abstinence DB abstinence OL OL NTX ER IM Placebo CNS Drugs.2013;27: Addiction. 2013;108(9): Naltrexone Implant Self report Opioid Use vs. Placebo Implant Systematic review and meta analysis Five randomized trials (n=576) Four non randomized trials (n=8358) Naltrexone implants were superior to placebo implants and oral naltrexone Krupitsky, 2012 Tihonen, 2012 Subtotal 95% CI high 95% CI low Risk Ratio Drug and Alcohol Review. 2014;33(2):

21 Buprenorphine Preparations Buprenorphine (Subutex ) Buprenorphine Implant (Probuphine ) Buprenorphine/Naloxone (Bunavail, Suboxone, Zubsolv ) Buprenorphine Preparations Controlled substance (C III) Drug Addiction Treatment Act (DATA) of 2000 Office based treatment Substance Abuse and Mental Health Services Administration (SAMHSA) waiver Comprehensive Addiction and Recovery Act (CARA) of 2016 Waivers for nurse practitioners and physician assistants American Society of Addiction Medicine (ASAM) Buprenorphine course for officebased treatment of opioid use disorders Required 8 hour training course for waiver application Patient load restrictions 30 patients in the first year 100 patients in the second year Up to a maximum of 275 patients with additional credentialing SAMHSA, SAMHSA, Buprenorphine Waiver Data Time Frame 30 Pt Limit % 100 Pt Limit % 275 Pt Limit % Total Past 30 days 1, ,572 Past 60 days 1, ,380 Past 90 days 3, ,065 Last Year 7, , , ,411 Current 27, , , ,211 SAMHSA,

22 Buprenorphine Waiver Data Ohio Time Frame 30 Patient Limit 100 Patient Limit SAMHSA, Buprenorphine Preparations Mechanism of Action (buprenorphine) Partial agonist µ opioid receptor Antagonist at κ opioid receptors Mechanism of Action (naloxone) Antagonist μ opioid receptor Preparations Buprenorphine 2 mg and 8 mg SL tablets Buprenorphine/Naloxone 2 mg/0.5 mg; 4 mg/1 mg; 8 mg/2 mg; 12 mg/3 mg film Contraindications Hypersensitivity to buprenorphine or naloxone Warnings Abuse Potential Respiratory Depression CNS Depression Unintentional Pediatric Exposure Dependence Hepatitis or Hepatic Events Allergic Reactions Precipitation of Opioid Withdrawal Signs and Symptoms and Neonatal Withdrawal Use in Opioid Naïve Patients Impaired ability to drive Adrenal Insufficiency Hepatic Impairment Orthostatic hypotension Elevated Cerebrospinal Fluid Pressure Elevation of Intracholedochal Pressure Acute Abdominal Conditions Buprenorphine prescribing information. Suboxone prescribing information. Buprenorphine Preparations Drug Interactions Cytochrome P450 3A4 inducers/inhibitors Anticholinergic drugs Antiretroviral Benzodiazepines CNS depressants Diuretics Muscle relaxants Serotonergic drugs Buprenorphine prescribing information. Suboxone prescribing information. 22

23 Buprenorphine Preparations Dosing (Maintenance) Titrated based on individual patient response Buprenorphine 4 24 mg per day Buprenorphine/Naloxone 4 mg/1 mg to 24 mg/6 mg per day Monitoring Abstinence from opioids Liver function tests Signs of overdose or withdrawal Adverse Effects Anxiety Asthenia Chills Constipation Headache Infection Insomnia Nausea Pain (i.e., abdominal and back pain) Sweating Vomiting Buprenorphine prescribing information. Suboxone prescribing information. Buprenorphine Preparations End of Phase Phase 2 end Phase of treatment wk post treatment Standard Medication Management SMM + Counseling Multi site randomized clinical trial Phase 1 Brief treatment 2 week buprenorphine naloxone stabilization 2 week taper 8 week post medication follow up Phase 2 Extended treatment 12 week buprenorphine naloxone treatment 4 week taper 8 week post medication follow up Arch Gen Psychiatry. Dec 2011;68(12): Methadone (Dolophine ) 23

24 Methadone (Dolophine ) Mechanism of Action Warnings μ opioid receptor agonist Respiratory depression N methyl D aspartate receptor antagonist Incomplete cross tolerance QT prolongation Contraindications Hypersensitivity to methadone Acute bronchial asthma Paralytic ileus Respiratory depression Acute abdominal conditions Alcohol or other drugs of abuse CNS depressants Dependence Head injury or increased ICP Hypotension Misuse, abuse, diversion Dolophine prescribing information. Methadone (Dolophine ) Drug Interactions Pharmacokinetic Considerations Anti retrovirals Absorption Arrhythmogenic agents CNS depressants Cytochrome P450 3A4 inducers and inhibitors Opiate agonists or antagonists Oral bioavailability % Time to peak plasma concentrations hours Distribution Protein bound 85 90% α 1 acid glycoprotein Metabolism Hepatic metabolism CYP3A4, CYP2B6, CYP2C19, CYP2C9, CYP2D6 Excretion Fecal and renal Dolophine prescribing information. Methadone (Dolophine ) Dosing (maintenance) Adverse Effects Initial dose mg based on previous use Common range mg Dizziness Lightheadedness Nausea Monitoring Sedation Sweating Abstinence from opiates Vomiting Cardiovascular effects Blood pressure Electrocardiogram Signs or symptoms of overdose or withdrawal Dolophine prescribing information. 24

25 Methadone Access Methadone products when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by opioid treatment programs certified by the Substance Abuse and Mental Health Services Administration and approved by the designated state authority. Dolophine prescribing information Dolophine prescribing information. Image from: stories?page=1. Methadone Detox vs. Maintenance Proportion using heroin at 6 months % at 11 months Median days in treatment MMT M180 Methadone detoxification (M180) vs. methadone maintenance therapy (MMT) (n=179) Mean methadone dose: M mg vs. MMT 86.3 mg Longer time in treatment with MMT Difference in heroin use at 6 months for MMT JAMA. 2000;283(10): Buprenorphine and Methadone 25

26 Assessment Question #6 Buprenorphine is more effective at maintaining abstinence of opiate use compared to methadone. A. True B. False Buprenorphine and Methadone 17 week double blind, double dummy RCT Four groups Buprenorphine naloxone 8/2 mg and 16/4 mg Methadone 45 mg and 90 mg Average % of doses ingested % 12 consecutive negative urines Mean retention in weeks Self report of days of heroin use Meth 90 Meth 45 BupNal 16 BupNal 8 Heroin Addict Rel Clin Problems2008;10(4):5 18. Buprenorphine and Methadone START Trial OUD patients Induction therapy then stabilization for 24 weeks with taper and follow up at week 32 Groups (n=1269) Buprenorphine/naloxone (n=740) Mean dose 22.1 mg/day Methadone (n=529) Mean dose 93.2 mg/day Complete Treatment Bup OR aor older aor heroin user Combined user J Stud Alcohol Drugs 2013;74:

27 Buprenorphine and Methadone * 31.8 * Maintenance treatment trial of inmates followed for 3 months post discharge Groups n=116 Buprenorphine/naloxone up to 32 mg (n=77) Methadone up to 70 mg (n=56) Primary Outcome * p<0.05 Bup/nal Methadone Treatment completion Reporting to assigned treatment modality after release Drug Alcohol Depend 2009;99(1 3): Buprenorphine and Methadone Cochrane Database of Systematic Reviews, Buprenorphine and Methadone Cochrane Systematic Database Reviews,

28 Buprenorphine and Methadone Cochrane Database of Systematic Reviews, Buprenorphine and Methadone: MOTHER trial Multi center, double blind, double dummy, flexible dosing, parallel group trial of pregnant women (n=175) Buprenorphine 2 32 mg (n=86) Methadone mg (n=89) Significantly more women discontinued buprenorphine treatment than methadone No difference in number of infants requiring Neonatal abstinence syndrome treatment Significantly lower doses of morphine and shorter length of stay for buprenorphine group * * * Discontinued Neonatal Infant LengthTotal amount therapy Abstinence of Stay of morphine Syndrome tx Methadone Buprenorphine * p<0.05 Addiction. 2012;107(1): N Engl J Med. 2010;363(24): Mini Case Study #3 A 27 year old patient with opioid use disorder (OUD) from taking prescription pain medication, has presented requesting information about medication assisted treatment options for their OUD. Which of the following is an accurate description of the differences between buprenorphine and methadone treatments for OUD? A. Buprenorphine treated patients tend to remain in treatment longer than methadone patients. B. Detoxification alone has better abstinence rates than maintenance treatment with either buprenorphine or methadone. C. Methadone tends to be less well tolerated than buprenorphine. D. Neither buprenorphine nor methadone is as effective as naltrexone. 28

29 Guidelines and Resources American Society of Addiction medicine National Practice Guidelines for the Use of Medications in the Treatment of Addiction Involving Opioid Use SAMHSA s Treatment Improvement Protocol 40: Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction The World Health Organization Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence The Department of Veterans Affairs/Department of Defense/Clinical Practice Guideline on Management of Substance Use Disorder Federation of State Medical boards Model Policy on the Drug Addiction Treatment Act of 2000 Treatment of Opioid Addiction in the Medical Office Summary There are three FDA approved treatment options for the maintenance treatment of Opioid Use Disorder: naltrexone, buprenorphine and methadone. Buprenorphine and methadone are preferred treatment options over naltrexone. Buprenorphine can be orders by prescribers with a waiver to be administered by the patient at home while methadone requires administration at a treatment program. Evidence does not support a clear superior choice between buprenorphine and methadone. References Ohio Association of Advanced Practice Nurses 29

30 References Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol dependent patients with liver cirrhosis: randomised, double blind controlled study. Lancet. 2007;370(9603): American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington (VA):American Psychiatric Publishing;2013. American Psychiatric Association. Practice guideline for the treatment of patients with substance use disorders. 2nd ed Available at: Accessed August 1, Anton RF, Kranzler H, Breder C, Marcus RN, Carson WH, Han J. A randomized, multicenter, double blind, placebo controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence. J Clin Psychopharmacol. 2008;28(1):5 12. Anton RF, O Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. 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