Kurt Haspert, MS, CRNP University of Maryland Baltimore Washington Medical Center

Data from the National Vital Statistics System Mortality The age-adjusted rate of drug overdose deaths in the United States in 2015 (16.3 per 100,000) was more than 2.5 times the rate in 1999 (6.1). Drug overdose death rates increased for all age groups, with the greatest percentage increase among adults aged 55 64 (from 4.2 per 100,000 in 1999 to 21.8 in 2015). In 2015, adults aged 45 54 had the highest rate (30.0). In 2015, the age-adjusted rate of drug overdose deaths among non-hispanic white persons (21.1 per 100,000) was nearly 3.5 times the rate in 1999 (6.2). The four states with the highest age-adjusted drug overdose death rates in 2015 were West Virginia (41.5), New Hampshire (34.3), Kentucky (29.9), and Ohio (29.9). In 2015, the percentage of drug overdose deaths involving heroin (25%) was triple the percentage in 2010 (8%). Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999 2015. NCHS data brief, no 273. Hyattsville, MD: National Center for Health Statistics. 2017.

Percentage of drug overdose deaths involving selected drug categories: United States, 2010, 2014, and 2015 Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999 2015. NCHS data brief, no 273. Hyattsville, MD: National Center for Health Statistics. 2017

Age-adjusted drug overdose death rates, by sex United States, 1999 2015 Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999 2015. NCHS data brief, no 273. Hyattsville, MD: National Center for Health Statistics. 2017

Source: Annual Overdose Death Reports, Maryland Vital Statistics Administration

DSM-V Definition Opiate Use Disorder Opioids are often taken in larger amounts or over a longer period than was intended A persistent desire or unsuccessful efforts to cut down or control opioid use A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects Craving, or a strong desire or urge to use opioids Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids Important social, occupational, or recreational activities are given up or reduced because of opioid use Recurrent opioid use in situations in which it is physically hazardous Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance Tolerance* Withdrawal* * Experiencing these symptoms while taking opioids solely under appropriate medical supervision is an exception to (does not meet) these criteria for OUD. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.

Medication Assisted Treatment MAT is a comprehensive approach that combines approved medications with counseling and other behavioral therapies to treat patients with opioid use disorder Scientific evidence suggests that maintenance treatment with these medications in the context of behavioral treatment and recovery support are more effective in the treatment of opioid use disorder than short-term detoxification programs aimed at abstinence, Nora D. Volkow, M.D Director of the National Institute on Drug Abuse (NIDA) Opioid detoxification may be good for a lot of things, but staying off opiates is not one of them Walter Ling, MD Professor Emeritus of Psychiatry and the Founding Director of the Integrated Substance Abuse Programs (ISAP) at UCLA

Pharmacotherapy FDA approved medications for the treatment of an opioid use disorder 1. Full opiate agonist: Methadone 2. Partial opiate agonist Buprenorphine 3. Opiate antagonist Naltrexone/Vivitrol

Counseling and other Behavioral Therapies Psychosocial and Behavioral Different Levels of Care Inpatient Residential Outpatient Partial Hospitalization Program (PHP Intensive Outpatient (IOP) Outpatient Peer Based Recovery Support Alcoholics Anonymous & Narcotics Anonymous SMART Recovery Peer Support Specialists

Pharmacotherapy Opiate Agonist and Partial Agonist Clark et al. (2015) Journal of Substance Abuse Treatment.57,75-80

Methadone Full Agonist Goals of treatment Suppress opioid withdrawal. Block the effects of illicit opioids. Reduce opioid craving and stop or reduce the use of illicit opioids. Promote and facilitate patient engagement in recovery oriented activities including psychosocial intervention. Withdrawal management with methadone must be done in an Opioid Treatment Program or inpatient setting There are 2 exceptions!!! The American Society of Addiction Medicine (2015) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use

Exceptions If a patient has an opioid dependency and is admitted to the hospital for a primary medical problem other than opioid dependency, such as a myocardial infarction, the patient may be administered methadone or buprenorphine to prevent opioid withdrawal that would complicate the primary problem [Title 42 Code of Federal Regulations 8.11.i2]. If a patient reports to the hospital with opioid withdrawal as a primary problem, the patient may be treated for no more than 3 days. This is an exception made by the DEA [Title 21, Code of Federal Regulations, Part 1306.7(b)] and is also known as the 3 day rule. For the 3 day rule, the following conditions must be implemented: 1. Not more than one day s medication may be administered or given to a patient at one time. 2. Treatment may not be carried out for more than 72 hours. 3. The 72-hour period cannot be extended or renewed.

Adverse Reactions Contraindicated Methadone Hypersensitivity Warnings and Precautions Cardiac conduction effects Respiratory depression Diversion and misuse are possible Severe bronchial asthma or hypercapnia Physical dependence Paralytic ileus Drug interactions with medications metabolized by cytochrome p450 Pregnancy - metabolism may need increased dose

Safety Faul M, Bohm M, Alexander C. Methadone Prescribing and Overdose and the Association with Medicaid Preferred Drug List Policies United States, 2007 2014. MMWR Morb Mortal Wkly Rep 2017;66:320 323

Buprenorphine Partial Agonist Goals of treatment Suppress opioid withdrawal. Block the effects of illicit opioids. Reduce opioid craving and stop or reduce the use of illicit opioids. Promote and facilitate patient engagement in recovery oriented activities including psychosocial intervention. Access to Care Drug Addiction Treatment Act of 2000 (DATA 2000) 8 hour training to prescribe buprenorphine Comprehensive Addiction and Recovery Act (CARA) 24 hour training to prescribe buprenorphine Waiver gives the prescriber the ability to prescribed buprenorphine in office-based settings.

Formulations Buprenorphine (Subutex) -Sublingual Tablet - Used mostly in pregnant patients Suboxone (Buprenorphine + naltrexone) - Sublingual Film - Also available as a generic tablet Zubsolv - Sublingual Tablet - Maryland Medicaid preferred choice Bunavail -Sublingual Film Probuphine -Subdermal Inplant -Requires specific Risk Evaluation and Mitigation Strategy (REMS) training

Peak Effect

Phases of Buprenorphine Treatment Induction Find the patient's ideal daily dose of buprenorphine to minimizes side effects and craving 12 to 16 mg/day 2 to 4 days Stabilization 6 to 8 weeks following induction. Patient is no longer experiencing withdrawal symptoms or intense cravings. Main goal of stabilization is to eliminate opioid use - patient reports - confirmed by urine drug testing. Maintenance Maintenance phase lasts indefinitely (SAMHSA 2004). Long-term maintenance is recommended due to high relapse rates. For example, in one study of 255 individuals, approximately 87% relapsed at 3 months (Ling 2009). During this phase, the patient is maintained at a comfortable dose and reports minimal craving or side effects.

Pharmacotherapy Opiate Agonist and Partial Agonist Clark et al. (2015) Journal of Substance Abuse Treatment.57,75-80

Adverse Effects Generally well tolerated Side effects reported with these medications include Headache Anxiety Constipation Perspiration Fluid retention in lower extremities Urinary hesitancy Sleep disturbance QT-interval prolongation does not seem to be an adverse effect associated with treatment with buprenorphine Patients with opioid use disorder and concurrent alcohol, sedative, hypnotic, or anxiolytic use disorders should receive more intensive monitoring during office-based treatment with buprenorphineto minimize the risk of adverse events

Safety Emergency department (ED) visits involving buprenorphine increased substantially from 3,161 in 2005 to 30,135 visits in 2010, as availability of the drug increased In 2010, most buprenorphine-related ED visits were classified as nonmedical use of pharmaceuticals (52 percent, or 15,778 visits), followed by patients seeking detoxification or substance abuse treatment (24 percent, or 7,372 visits) and adverse reactions (13 percent, or 4,017 visits) Buprenorphine-related ED visits involving nonmedical use of pharmaceuticals increased 255 percent from 4,440 visits in 2006 to 15,778 visits in 2010 Additional drugs were involved in 59 percent of buprenorphine-related ED visits involving nonmedical use of pharmaceuticals in 2010 Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. (January 29, 2013). The DAWN Report: Emergency Department Visits Involving Buprenorphine. Rockville, MD.

Buprenorphine vs. Methadone Cochrane Database of Systematic Reviews (2016) Low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence Methadone or buprenorphine appeared equally effective Clinician or treatment system factors may contribute to the choice of pharmacotherapy Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments.

Naltrexone - Antagonist Goals of treatment To prevent relapse to opioids in patients who have already been detoxified and are no longer physically dependent on opioids Block the effects of illicit opioids. Reduce opioid craving and stop or reduce the use of illicit opioids. Promote and facilitate patient engagement in recovery oriented activities including psychosocial intervention. Formulations Oral Naltrexone Extended-Release Injectable Naltrexone For patients in occupations that do not permit opioid agonist treatment In areas such as public safety, transport of hazardous materials, licensed drivers, and healthcare, some employees are not allowed to use methadone and, in some cases, buprenorphine.

Formulations Oral Naltrexone (Revia) Important that the patient has been adequately detoxified from opioids and is no longer physically dependent Patients should be free from short-acting opioids for about 6 days before starting naltrexone Patients should be free from long-acting opioids such as methadone and buprenorphine for 7 10 days.? Naloxone challenge Oral naltrexone seems to be most useful when there is a support person to administer and supervise the medication Extended-Release Injectable Naltrexone (Vivitrol) Give every 4 weeks by deep intramuscular injection Naltrexone dosing before re-entry (incarceration/inpatient rehab) may serve to prevent relapse and overdose Injection site reactions May be more suitable for patients who have issues with adherence.

Adverse Effects Both oral and extended-release injectable generally well tolerated Side effects reported with these medications include Insomnia Lack of energy/sedation Anxiety Nausea and/or vomiting Abdominal pain/cramps Headache, Cold symptoms Extended-release injectable naltrexone injection site reactions There is no recommended length of treatment with oral naltrexone or extended-release injectable naltrexone. Duration depends on clinical judgment and the patient s individual circumstances Because there is no physical dependence associated with naltrexone, it can be stopped abruptly without withdrawal symptoms

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