Disclosures None Preventing, Recognizing and Managing Opiate Use Disorders Katherine Julian, M.D. Professor of Medicine UCSF Division of General Internal Medicine December 7, 2017 Rates of Prescription Medication Opioids in the US… Abuse – Ages 12+ Pain as the “Fifth Vital Sign” Ever Use Use in Last Year US consumes 80% of the world’s opiates (2014) Pharm companies spent $880 million between Non-Medical Use of 20.5% 5.6% 2006 and 2015 to influence federal and state Psychotherapeutics opioid policies Pain Medications 13.6% 3.9% Abuse deterrent formulations don’t prevent patients Sedatives 3% 0.3% from taking higher doses than prescribed; not “abuse-proof” Prevalence of heroin use/use disorder increasing http://www.samhsa.gov/data/sites/default/files/NSDUH- DetTabs2014/NSDUH-DetTabs2014.pdf
Opiate Non-Medical Use Question #1 Non-Medical Use=Use without a prescription or What is the most common source of pain for the feeling the drug caused relievers for non-medical use? Associated with increased mortality (HR 1.60) A) One doctor 1960’s: 80% reported first opioid was heroin B) Free from friend/relative 2000’s: 75% reported first opioid was prescription C) The internet opioids D) From stranger/drug dealer E) More than one doctor Colter LB et al, Am J Public Health, 2016; Compton WM, et al. N Engl J Med 2016 Age-Adjusted Rates of Death Related to Prescription Opioids and Heroin Drug Poisoning in Source Where Pain Relievers Were Obtained for Most Recent the United States, 2000–2014. Nonmedical Use among Past Year Users Aged 12 or Older: 2012-2013 Compton WM et al. N Engl J Med 2016;374:154-163 SAMHSA 2014
Outline DSM5 - Substance Use Disorder Substance Use Disorders No longer need to differentiate between Definitions substance abuse and substance dependence Screening Each substance can be categorized as a disorder Pharmacology of Opiates Ex: Alcohol use disorder, stimulant use Opiate Use Disorder Pharmacotherapy disorder, opioid use disorder, etc Treatment of Non-Cancer Pain Grade Severity: Mild, Moderate, Severe Balance risks/benefits of opiate therapy DSM5 - Substance Use Disorder Criteria for Substance Use Disorder Failure to fulfill role obligations Recurrent substance use in situations that are physically “Maladaptive pattern of substance use leading to hazardous clinically significant impairment or distress, as Persistent use despite social/interpersonal problems manifested by 2 (or more) of the following, occurring Tolerance Withdrawal within a 12-month period:” Using more than originally intended Persistent desire or unsuccessful efforts to cut-down Time spent obtaining/using substance or recovering from side effects Reduction of social/occupational activities Use despite physical/psychological problems Craving
DSM5 - Substance Use Disorder Opiate Use - How to Screen? Ask permission: “Would it be ok to spend the Of the 11 items: next few minutes talking about drug use?” Need 2 criteria for SUD Single Drug Use Screen Question: 2-3 criteria =mild SUD How many times in the past year have you 4-5 = moderate SUD used an illegal drug or used a prescription >6 = severe SUD medication for nonmedical reasons? Positive Screen=1 or more Smith PC, et al. J Gen Intern Med 2009;24(7); NIAAA Guidelines 2005 Determining “At Risk” vs. A Positive Screen… “Substance Use Disorder” What to do next? Assess… Pts with positive screen should get a brief intervention Ask which drugs the patient has been using Determine frequency/amounts Patients who meet substance use disorder criteria Ask about negative impacts abuse should get a Brief intervention The follow-up questions assess impact and determine AND whether he/she has a substance use A referral to specialty care (if they are willing) disorder diagnosis. AND Be considered for pharmacotherapy
What is a Brief Intervention? Brief Intervention Short motivational interviews that encourage “Based on your screening results, you are at high risk of patients to create a plan of action that is based having a substance use disorder. I am concerned if you do not make a change quickly, the consequences to on their willingness to change their behavior your health may be serious.” Non-judgmental, direct, honest feedback “I strongly recommend that you quit and I’m willing to If not ready to change → harm reduction help” Plan for follow-up “Are you willing to consider making changes in your Mixed data for at-risk drug use drug use?” How to Help Patients: A Clinical Approach: NIAAA 2005 Resource for Clinicians Abuse.gov Motivational Interviewing Background - Types of Opioids Type Source Examples Express empathy, develop Natural Opiates From the poppy Morphine, Thebaine, discrepancy, support self-efficacy Codeine, Opium Semi-Synthetic From the poppy but Heroin, Oxycodone, processed Hydrocodone, Some possible tools: Hydromorphone Synthetic Designed in lab Methadone, Fentanyl, OARS (open-ended questions, affirmations, Meperidine reflections, summary statements) Listen for “change talk” Readiness to change ruler Importance/confidence ruler
Background - Opioid Receptors Background - Opioid Receptors Receptor affinity = strength with which a drug Found peripherally and centrally physically binds to receptor Central (brain, spinal cord) most important for Buprenorphine, naloxone, naltrexone have strong controlling pain affinity Also bind endogenous opioid peptides Will displace heroin, methadone from mu receptor (endorphins) Receptor dissociation = the speed of uncoupling Several types of opioid receptors, but analgesia of a drug from the receptor largely from action on mu receptors Dissociation of buprenorphine and naltrexone is slow Background - Opioid Receptors Pharmacotherapies for Opiate Dependence Function at receptors = does drug activate receptor? Methadone Full agonist binding : highly reinforcing is most misused Buprenorphine (ex: heroin) Naltrexone Antagonist binding : occupies receptor without activating (ex: naloxone) Partial agonist binding : activates receptor at low levels but less reinforcing (so less misused) = buprenorphine
Opioid Dependence Maintenance Opioid Dependence Maintenance Therapy: Methadone Therapy: Methadone Can only be prescribed through a registered Variable and complex pharmacodynamics so “narcotic treatment program” caution with titration Long acting mu agonist (24-36h) Many drug interactions Peak levels 4 hours; average half-life 24 hours Side effects 30-40 mg will block withdrawal, but not craving Constipation, weight gain, lowered libido QT prolongation (approx 2%) 80-100 mg is more effective at reducing opioid use EKG at start, 1 month, every 3-6 months than lower doses (e.g.: 40-50 mg/d) Discontinue if QTc > 490 ms Strain EC, et al. JAMA, 1999 Strain EC, et al. JAMA, 1999 Opioid Dependence Maintenance Opioid Dependence Maintenance Therapy: Buprenorphine Therapy: Buprenorphine Mu Opioid receptor, high affinity, partial agonist Relieves withdrawal symptoms in patients already Slow to dissociate in withdrawal, less physical dependence capacity If recent opioids, may withdraw Little effect on respiration or cardiovascular responses at high doses OD can’t be reversed with standard dosing of naloxone Active metabolite: nor-buprenorphine Half-life > 24 hours McNicholas, Center for Substance Abuse Treatment 2004 McNicholas, 2004
Opioid Dependence Maintenance Opioid Dependence Maintenance Therapy: Buprenorphine Therapy: Buprenorphine To reduce diversion, combined with naloxone in Poor oral bioavailability 4:1 ratio Sublingual Cheaper price than buprenorphine alone! Buccal Occas increase in LFTs Implant Probuphine (approved 5/26/16)* SE: N/V (?if due to withdrawal), minimal sedation Implant will give steady low-level amount of medication for six months Equivalent to lower dose of methadone in reducing illicit opioid use (though 80mg methadone better) Studied in patients on stable oral dose (8mg or less) for >90 days. Must be trained in placement/removal. Buprenorphine DEA certification required to *Use only in patients “who are already stable on low-to- prescribe for opiate use disorder (8 hrs of training) moderate doses of other forms of buprenorphine, as part of a complete treatment program” Opioid Dependence Therapy: Opioid Dependence Therapy: Antagonist Treatment (Naltrexone) Antagonist Treatment (Naltrexone) Mu receptor antagonist Dose (oral): 50 mg daily, 100 mg every 2 days, 150 mg every third day Relapse rates high (90%) following detoxification with no medication treatment Dose (IM): 380mg IM q month Prevent impulsive use of drug Side effects Requires full withdrawal before initiation or Nausea, headache, dizziness severe withdrawal will be precipitated Blocks effect of opioid analgesics 3-6 days off short-acting opiate Hepatotoxicity, monitor liver function tests every 3 months 7-10 days off long acting opiate Biggest issue is lack of compliance Risk of overdose if medication stopped Schuckit MA. N Engl J Med, 2016 Schuckit MA. N Engl J Med, 2016
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