Opioids and Opioid Addiction: Practical Management Approaches Yngvild Olsen, MD, MPH Medical Director Institutes for Behavior Resources Inc/REACH Health Services
Conflict of Interest No financial or advisory relationships related to this activity
LEARNING OBJECTIVES Understand the key scientific and diagnostic elements of opioid use, opioid use disorder, and opioid addiction Describe the different options and role of medication-assisted treatment for opioid use disorder Understand the regulatory environment for use of opioids, treatment of opioid use disorders, and how this impacts patient management
Maryland statistics http://bha.dhmh.maryland.gov/overdose_prevention/siteassets/pages/data-and- Reports/Quarterly%20report_2nd%20quarter%202016%20(1).pdf
Frank B. 28 yo male comes for a new patient visit on a Friday afternoon. You get a call from receptionist he s 15 minutes late so I told him we would need to reschedule but he s demanding to see you now and won t leave. Slightly disheveled, unshaven, wearing dirty jeans and a worn sweatshirt. Grumbles this is f.. up under his breath Demands a prescription for a controlled medication Your initial reaction?
Physician Attitudes and SUD Attitudinal surveys of medical students and residents demonstrate low regard for patients with SUDs Compared to hypertension, dyspepsia, pneumonia Lowest for opioid use disorder compared to alcohol use disorder Low levels of satisfaction caring for addicted patients among physicians in practice Some evidence that attitudes towards patients with SUD degrade over course of training and practice
Public Perception of Addiction Barry et al 2014: National randomized public opinion survey on mental illness and addiction 54% to 90% of respondents thought employment and housing could be denied to those with addiction, did not want to have co-workers with addiction, or want them to marry into family 15% to 59% thought the same for mental illness 43% opposed insurance parity for addiction vs 21% for mental illness Barry C et al. Psych Serv 2014
Brain Disease Model and Public Attitudes Australian social survey 2012*: Over 1,200 residents in Queensland Asked for level of agreement on a number of questions about: causality of addiction, disease models, role of coerced treatment, stigma, discrimination, and dangerousness Key Results: Over 50% believed alcohol and heroin addiction was a disease; only about 30% thought both were a brain disease 60% thought addiction was caused by personal character qualities Attitude is a little thing that makes a big difference ** *Meurk et al. BMC Psychiatry, 2014. **Ballon in Academic Psychiatry, 2008
Addiction Etiology Theories Moral failing or insufficient willpower VS Reward deficiency syndrome Deficiency of inhibitory control Disorder of choice Conditioned learning and habituation Self-medication of unrecognized underlying psychiatric disorder Disorder of bonding and connectedness To other humans To spiritual being
The Reward Pathway Source: NIDA. www.drugabuse.gov
Source: NIDA. www.drugabuse.gov The Human Brain
Pathophysiology of Addiction
THE BASIS FOR ADDICTION AS A DISEASE THE PERFECT STORM! Source: NIDA
Genetic Variants of the Human Mu Opioid Receptor: Single Nucleotide Polymorphisms in the Coding Region Including the Functional A118G (N40D) Variant HYPOTHESIS Gene variants: Alter physiology PHYSIOGENETICS Alter response to medications PHARMACOGENETICS Are associated with specific addictions Slide Source: Dr. Kreek Bond, LaForge Kreek, Yu, PNAS, 95:9608, 1998; Kreek, Yuferov and LaForge, 2000
Lifetime Prevalence and Odds Ratios of Mental Disorders by Substance Use Disorder: ECA Alcohol Drug Comorbid Disorder % O.R. % O.R. Any mental 36.6 2.3 53.1 4.5 Schizophrenia 3.8 3.3 6.8 6.2 Affective 13.4 1.9 26.4 4.7 Anxiety 19.4 1.5 28.3 2.5 Antisocial 14.3 21.0 17.8 13.8 (Regier et al., JAMA 264:2511-2518, 1990)
Trauma Impact Adverse Childhood Experiences Study: Over 8,000 adult men and women (mean age 57 and 55, respectively) Assessed history until age 18 of abuse/neglect, level of household dysfunction, health-related behaviors, and illicit drug use using standardized questionnaires Each participant assigned an ACE score based on number of experiences (analyzed as 0-5+) 67% had at least ACE; 42% had 2 or more Dube et al. Pediatrics, 2003
ACE Study Results: Initiation of Illicit Drug Use
ACE Study Results: Substance Use Disorder
Age of First Use Multiple studies demonstrate higher risk of adult onset substance use disorders with early onset of use before age 14 Higher vulnerability of adolescent brain -- significant developmental changes Changes in dopaminergic system Growth in prefrontal cortex Refinement of limbic neurocircuits Differential gene expression during adolescence compared to adulthood
Addictive Potential Determinants The faster a drug gets to the brain, the higher addictive potential The shorter acting a drug is, the higher addictive potential More potent drugs have higher addictive potential Takes less of drug to achieve effect
Addiction Definition A primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations.* A chronic, relapsing disease characterized by compulsive drug seeking and use despite harmful consequences as well as neurochemical and molecular changes in the brain.** A brain disease whose symptoms are overwhelming cravings and resultant behaviours. *American Society of Addiction Medicine **National Institute on Drug Abuse (NIDA)
Substance Use Disorder Diagnostic Criteria, DSM-5 More use than intended Excessive time spent in acquisition Unsuccessful efforts to cut down Activities given up because of use Craving for the substance Continued use despite consistent social or interpersonal problems Failure to fulfill major role obligations Tolerance* Use despite negative effects Withdrawal* Recurrent use in hazardous situations Severity measured by number of symptoms; 2-3 mild, 4-6 moderate, 7-11 severe * These do not apply if the medication is prescribed and no other diagnostic criteria are met
Physical Dependence Vs. Addiction Physical dependence is neither sufficient nor necessary to diagnose addiction. Dr. Howard Heit Physical dependence is a neuropharmacological phenomenon while addiction is both a neuropharmacological AND behavioral phenomenon. Physical dependence occurs with many different categories of medications and substances. Heit HA. Addiction, Physical Dependence, and Tolerance: Precise Definitions to Help Clinicians, Evaluate, and Treat the Patient with Chronic Pain. J Pain and Palliative Care Pharmacotherapy. March/April 2003;26:655-667
Connect and Disconnect
Components of Comprehensive Addiction Treatment www.drugabuse.gov
No cure! Chronic Disease Goal is life long management Disease severity may change over time but risk of symptom recurrence is always present Behavior change is a key part of management Behavior change occurs in stages Effective treatment often combines medications and behavioral interventions
Mu Receptor Activation Full agonist mu receptor site Partial agonist methadone buprenorphine mu receptor site Antagonist naltrexone mu receptor site
Activity Levels 100 90 Full Agonist (e.g. methadone) % Mu Receptor Intrinsic Activity 80 70 60 50 40 30 20 10 0 But due to its ceiling maximum opioid agonist effect is never achieved Partial Agonist (e.g. buprenorphine) Like full agonists, partial agonist drugs produce increasing mu opioid receptor specific activity at lower doses no drug low dose DRUG DOSE high dose
Opioid Agonist Response vs. Heroin Response
Benefits Of Treatment Reduces risk of HIV infection Reduces risk of infection with hepatitis C and B Increases rates of employment among patients as a group Decreases crime Increases length of life
Treatment Effectiveness For Opioid Use Disorder Reduces drug use by 40-70% Addiction treatment is as successful as treatment of diabetes, asthma, and hypertension Strongest predictor of recovery is retention in treatment
Treatment Outcomes For Tapering off Medication In methadone studies, 50-80% relapse within one year after taper 91% of patients receiving buprenorphine for 4 months had relapsed to prescription opioids within 2 months of taper* Opioid overdose fatality rates are 3 to 20 times higher in the month after tapering off than during treatment *Weiss R. et al. NIDA CTN Prescription Opioid Treatment Study. http://www.medscape.com/viewarticle/722342
Reduced Mortality
2.5 Opioid Overdose Mortality Rates Before, During, and After Treatment with Methadone (per 100 person-years) 2 1.5 1 0.5 0 Total Male Female Pre-Tx During Tx Post-Tx Clausen et al, Drug and Alc Depend 2008
Side Effects of Methadone and Buprenorphine Respiratory depression Sedation Constipation Decreased libido and sexual dysfunction Headache (primarily buprenorphine) Sweating (primarily methadone) Loss of appetite and dry mouth Nausea, vomiting Heart arrhythmias (high doses of methadone) Medication interactions Potential for misuse
Methadone/Buprenorphine and Other Substances Increased risk of acute opioid intoxication if mixed with alcohol Benzodiazepines potentiate sedative effects of opioids Overdoses have occurred in patients on buprenorphine and benzodiazepines Treatment may be needed for other substance use disorders but methadone or buprenorphine should be continued with appropriate dose adjustment to minimize sedation while balancing risk of illicit opioid relapse
Side effects of Naltrexone Nausea Fatigue Decreased appetite Insomnia Mild elevations in LFTs common, primarily with hep C Injection site reactions Precipitated withdrawal in opioid-tolerant individuals No long term studies past 12 months Significant drop out rates
Naltrexone and Other Substances Differences in individual metabolism of naltrexone noted Extremely high doses of heroin or fentanyl may override opioid blockade Approved for alcohol use DO Treatment still needed for other substances
Advancing Access to Addiction Medications National Guideline Conclusions The three pharmacotherapies have all shown clear clinical evidence of effectiveness in reducing opioid use and opioid use-related symptoms of withdrawal and craving as well as risk of infectious diseases and crime when used as part of a comprehensive treatment approach and in appropriate doses. The effectiveness of these medications is true only when used in continuing care, maintenance regimens; there remains almost no evidence of enduring benefits from any of these medications when used only in detoxification regimens. These medications have very different pharmacological properties and clinical roles. It is not presently known which of these medications is best for which type of patient or under which circumstance this should be the focus of additional research; particularly explorations of pharmacogenetic subtypes.
Indications for Medications All patients with opioid use disorder should be offered medication as a component of treatment The choice of medication is a medical decision between a physician and a patient Weighing complete history, physical examination, and relevant laboratory testing Factors to consider Methadone heavily structured and regulated Buprenorphine is expensive but less structured Naltrexone contra-indicated if prescription opioids are part of chronic pain treatment
HOW LONG IS LONG ENOUGH? Dennis M, et al, Eval Rev, 2007
Medications and Recovery SAMHSA recovery definition A process of change through which individuals improve their health and wellness, live a self-directed life, and strive to reach their full potential DSM 5 remission definitions 1. In early remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met for at least 3 months but for less than 12 months. 2. In sustained remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met at any time during a period of 12 months or longer. 3. On maintenance therapy: This additional specifier is used if the individual is taking a prescribed agonist medication such as methadone or buprenorphine and none of the criteria for opioid use disorder have been met for that class of medication (except tolerance to, or withdrawal from, the agonist). This category also applies to those individuals being maintained on a partial agonist, an agonist/antagonist, or a full antagonist such as oral naltrexone or depot naltrexone.
JAMA. 1913;60(6):431-434.
MANY PATHS TO RECOVERY!
Resources Advancing Access to Addiction Medications http://www.asam.org/docs/defaultsource/advocacy/aaam_implications-for-opioidaddiction-treatment_final ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use http://www.asam.org/docs/default-source/practicesupport/guidelines-and-consensus-docs/national- practiceguideline.pdf?sfvrsn=18 Maryland Behavioral Health Administration http://bha.dhmh.maryland.gov/sitepages/home.aspx Provider Clinical Support System Medication Assisted Treatment pcssmat.org
Questions? yolsen@ibrinc.org 410-752-6080 x119