Addiction Medicine - Substances of Abuse Bradley J. Miller, DO

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1 Addiction Medicine - Substances of Abuse Bradley J. Miller, DO

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3 Practical Approaches to Managing Substance Abuse and Nicotine Addiction ACOFP Intensive Update and Board Review in Osteopathic Family Medicine Bradley J. Miller, DO, FAAFP Williamsport Family Medicine Residency Objectives Review current statistics and disease burden of substance abuse in the United States. Describe importance of screening for, provide brief intervention for, and recognize when to refer to treatment for substance abuse disorders in the primary care setting. Review specific substances of abuse (alcohol, nicotine, MJ, opiates) and accepted pharmacologic treatments Question # 1 In patients who die from an opioid overdose, a second substance is often present that contributes to the patient s death. Which one of the following additional substances is most likely to be found in conjunction with a fatal opioid overdose? A) THC (Marijuana) B) Antidepressants C) Cocaine D) Benzodiazepines E) Alcohol 1

4 Current Statistics and Disease Burden 2012 National Survey on Drug Use and Health 23.9 million people over 12 years are current illicit drug users 52.1% of individuals over 12 years report being current drinkers Of all individuals over 12 years who drink 23% binged in the last month 6.5% participate in heavy drinking Current Statistics and Disease Burden 2.1 M ED visits associated with drug misuse or abuse in 53% of all ED visits involved pharmaceuticals Pain relievers- most common Other pharmaceuticals included BZDs alprazolam most reported Substance Abuse and Mental Health Services Administration, Drug Abuse Warning Network, 2009: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) , DAWN Series D-35. Rockville, MD: Substance Abuse and Mental Health Services Administration, SAMHSA National Survey Past Month Use of Selected Illicit Drugs among Youths Aged 12 to 17: Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) Rockville, MD: Substance Abuse and Mental Health Services Administration,

5 SAMHSA National Survey Past Month Nonmedical Use of Types of Psychotherapeutic Drugs among Persons Aged 12 or Older: Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013 Mokdad et al., 2004 SAMHSA National Survey Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year Users Aged 12 or Older: Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) Rockville, MD: Substance Abuse and Mental Health Services Administration,

6 Top Medications Prescribed 2011 Enough opiate pain medications were prescribed in 2010 to medicate every American adult with 5 mg of hydrocodone taken every 4 hours for an entire MONTH Warner M, Chen LH, Makuc DM. Increase in fatal poisonings involving opioid analgesics in the United States, NCHS data brief, no 22. Hyattsville, MD: National Center for Health Statistics Vital Signs: Overdoses of Prescription Opioid Pain Relievers United States, MMWR Volume 60, No. 43. pp November 4, 2011 Death Rates* for Three Selected Causes of Injury National Vital Statistics System, United States, Center for Disease Control, Morbidity and Mortality Weekly, November 21,

7 The Neurochemistry of Addiction Dopamine: Amphetamines, cocaine, alcohol Serotonin: LSD, alcohol Endorphins: Opioids (heroin and narcotics), alcohol GABA: Benzodiazepines, alcohol Glutamate: Alcohol Acetylcholine: Nicotine, alcohol Endocannabinoids: Marijuana, alcohol SCREENING Alcohol What is Low-Risk Drinking?: Females < 7 drinks per week < 3 drinks per occasion Males < 14 drinks per week < 4 drinks per occasion Adults over 65 years of age < 7 drinks per week < 3 drinks per occasion 5

8 Alcohol What constitutes 1 drink?* Beer 12 ounces Shot 1.5 ounces Wine 5 ounces * The definition of a standard drink varies from country to country and study to study; the above is the WHO definition, and is used by the SBIRT initiative What is a standard drink? One 12oz. Can/Bottle of Beer A single shot (1.5 oz.) of distilled spirits (gin, vodka, rum, etc ) A glass of wine (5 oz.) or a small glass of sherry DSM-IV SUD Substance Abuse 1 or more of the following at the same time in a 12-month period: Recurrent use resulting in failure to fulfill major role obligations Recurrent use in situations that are physically hazardous Recurrent legal problems resulting from use Continued use despite having persistent social or interpersonal problems caused or exacerbated by the substance Does not meet criteria for Dependence Substance Dependence 3 or more of the following at the same time in a 12-month period: Tolerance Withdrawal Taken in larger amounts or over longer period than intended Persistent desire or unsuccessful efforts to cut down Great deal of time spent in obtaining, using, and recovering from substance Important activities are given up as a result of substance use Use continues despite knowledge of physical or psychological problem that is caused or exacerbated by the substance 6

9 DSM-V Substance Related Disorders A major overhaul of the DSM-IV criteria for substance use includes the following: Substance Use Disorder (SUD) is a single disorder, measured on a continuum from mild to severe, that combines the DSM-IV abuse and dependence criteria with the following two exceptions: DSM-IV recurrent legal problems has been removed New criterion for craving or a strong desire or urge to use has been added Each specific substance is addressed as a separate use disorder (e.g. alcohol use disorder, opiate use disorder) Cannabis and Caffeine withdrawal are new for DSM-V Gambling disorder has been added DSM-V Substance Use Disorder SUD is accompanied by criteria for intoxication, withdrawal, substance/medication-induced disorders and unspecified substanceinduced disorders. The severity of SUD in DSM-V is based on criteria endorsed: 2-3 mild disorder 4-5 moderate disorder 6 or more severe disorder Helps define SUD as a continuum and removes confusion regarding dependence with addiction when in fact dependence can be a normal body response to a substance Additional modifiers and specifies exist as well. Substance INTOXICATION & WITHDRAWAL are different codes and are dependent on the severity of the SUD National Institute on Alcohol Abuse and Alcoholism NIH Publication No November

10 Question # 2 A 67 year old male with was brought to the emergency department after his friend found him confused at home. The patient typically drinks up to 12 cans of beer daily but has increased over the past 2 months. He has had some falls while intoxicated over the past year and has tried to cut down but hasn t been able to do so. His family has been encouraging him to cut down and he has been unsuccessful. He decided to stop drinking and his last drink was about 20 hours ago. When found, the patient referred to his friend as his wife who has been deceased for 2 years. Which of the following is most accurate? (A) The patient meets diagnostic criteria for moderate alcohol use disorder and is beginning to have delirium tremens (B) The patient meets diagnostic criteria severe alcohol use disorder and is beginning to have delirium tremens (C)The patient meets diagnostic criteria for moderate to severe alcohol use disorder and is beginning to have alcohol hallucinations (D) Naltrexone, thiamine and folate should be given to the patient prior to treatment with lorazepam (E) None of the above Alcohol Alcohol Withdrawal Syndromes Pathophysiology of ETOH withdrawal Abrupt withdrawal unmasks compensatory over-activity of the nervous system. Alters levels of GABA, Norepinephrine and Serotonin Minor Withdrawal Symptoms Due to CNS and sympathetic hyperactivity Usually present within 6 hrs of drinking cessation Insomnia, tremulousness, anxiety, GI upset, HA, diphoresis, palpitations, or anorexia Resolve within hours consistent from one episode to the next 8

11 Alcohol Withdrawal Syndromes Withdrawal Seizures Usually tonic-clinic convulsions within 48 hours of last drink 3% of chronic alcoholics have withdrawal seizures of which 3% develop status epilepticus Usually a singe episode. Recurrent or prolonged seizures require investigation of another source Alcohol Withdrawal Syndromes Alcoholic Hallucinations Often mistaken for delirium tremens (DTs) Hallucinations that develop hrs from abstinence and resolve within hrs (which is when DTs typically begin) Usually visual but can be auditory and tactile Usually associated with specific hallucinations and not global clouding of the sensorium (as with DTs) Alcohol Withdrawal Syndromes Delirium Tremens Occurs in 5% of pts experiencing withdrawal Hallucinations, disorientation, tachycardia, HTN, low grade fever, agitation, and diaphoresis. Typically begin between 48 & 72 hrs and last one to five days Mortality rate of 5% death usually from arrhythmias or complicating illnesses such as pneumonia 9

12 Treatment Inpatient vs outpatient For all patients: 1. Thiamine 100mg oral/iv daily (before glucose containing fluids to avoid Wernicke encephalopathy) 2. Folate 1 mg oral for 3 days Outpatient Pharmacotherapy for ETOH Dependence Three agents approved by FDA for adjunctive therapy for the treatment of alcohol dependence (other agents exist) Naltrexone Pure opioid receptor antagonist Blunts pleasurable effects of alcohol and reduces cravings Reduces relapse and number of drinking days CAUTION: Will cause opiate withdrawal! BLACK BOX WARNING-acute hepatic toxicity Naltrexone PO (ReVia ) / IM Depot (Vivitrol ) Typical starting and maintenance oral dose is 50mg daily High risk patients should start at 12.5mg or 25mg and titrate up OR 380mg IM q 4 weeks 10

13 Outpatient Pharmacotherapy for ETOH dependence Acamprosate (Campral) Structural analog of GABA Decreases excitatory glutameric neurotransmission during withdrawal 666 mg TID. May need to adjust if pt has diarrhea Disulfiram (Antabuse) Deterrent- causes flushing, nausea, vomiting, tachycardia, dyspnea, HA, blurred vision, vertigo and anxiety minutes after ingestion of ETOH Indications for inpatient alcohol detoxification Indications for inpatient alcohol detoxification - History of severe withdrawal symptoms - History of alcohol withdrawal seizures or DTs - Multiple past detoxifications - Other medical or psychiatric illness - Recent high levels of alcohol consumption - Lack of reliable support network - Pregnancy Myrick,H. Treatment of alcohol withdrawal. Alcohol Health and Research World, 1998, Vol.22 Issue 1, Treatment Gradual Tapering Regimen - predetermined dosing schedule for several days as the medication is gradually discontinued (mostly used outpatient) 11

14 Treatment One of the following: 1. Chlordiazepoxide (Librium ) mg every 6 hours for 4 doses then mg every 6 hours for 8 doses 2. Diazepam (Valium ) 10-20mg every 6 hours for 4 doses then 5-10mg every 6 hours for 8 doses 3. Lorazepam (Ativan ) 2-4 mg every 6 hours for 4 doses then 1-2 mg every 8 hours for 8 doses (medication of choice with hepatic dysfunction) 4. Carbamazepine (Tegretol ) 200 mg QID x 1 day 200 mg TID x 1 day 200 mg BID x 1 day 200 mg BID x 1 day 200 mg daily x 2 days Asplund.C. Three regimens for alcohol withdrawal and detoxification. The Journal of Family Practice. July Vol. 53. Treatment Fixed Schedule Regimen 1. Diazepam (Valium ) Dose: mg PO q1h prn while awake Endpoint: until adequate Sedation 2. Lorazepam (Ativan ) Dose: 1-2 mg IV q1h prn while awake for 3-5 days Endpoint: until adequate Sedation 3. Chlordiazepoxide (Librium ) Dose: 50 to 100 mg PO/IM/IV q4h (max: 300 mg/day) Endpoint: until adequate Sedation Associated with overmedication Moses,S. Alcohol Withdrawal. Treatment Symptom-Triggered Regimen - Pt withdrawal score is determined hourly or bihourly and the medication is administered only when the score is elevated >8 on clinical withdrawal scale 12

15 Treatment Clinical Institute Withdrawal Assessment Revised Scale (CIW-Ar) <10: Very mild withdrawal 10-15: Mild withdrawal 16-20: Modest withdrawal >20: Severe withdrawal Smith,M. Management of alcohol intoxication and withdrawal. Principles of Addiction Medicine. 4th edition Additional Interventions Phenobarbital or propofol for refractory DTs May require mechanical ventilation and ICU admission Phenothiazines and butyrophenones (including Haldol) AVOID- lower seizure threshold Anticonvulsants- controversial if effective. Most seizures are self limited and do not require medication Consider phenytoin Question # 3 The five A s Model for treating tobacco abuse and dependence include all of the following except A Ask about tobacco use on every patient B Advise to quit C Assess willingness to made a quit attempt D Assist in the quit attempt E Arrange for nicotine support group 13

16 Nicotine Nicotine Tobacco is the chief avoidable cause of illness and death in our society Accounts for more than 435,000 deaths/yr 45 million smokers in the United States 70% of them want to quit 20 million attempt to quit each year, unaided only 4-7% are successful Dependence among users Difficulty achieving abstinence nicotine>heroin>cocaine>alcohol>caffeine (alcohol=cocaine=heroin=nicotine)>caffeine Tolerance (alcohol=heroin=nicotine)>cocaine>caffeine Physical alcohol>heroin>nicotine>cocaine>caffeine withdrawal severity Deaths Importance in user's daily life Prevalence nicotine>alcohol>(cocaine=heroin)>caffeine (alcohol=cocaine=heroin=nicotine)>caffeine caffeine>nicotine>alcohol>(cocaine=heroin) 14

17 The 5 A's Model for Treating Tobacco Use and Dependence Ask about tobacco on every patient Advise to quit. Assess willingness to make a quit attempt. Assist in quit attempt Arrange follow up First-Line Medications Nicotine Replacement Therapy (NRT) -Patch (OTC) -Gum (OTC) -Lozenge (OTC) -Oral Inhaler (Rx) -Nasal Spray (Rx) Non-Nicotine Medications -Varenicline (Chantix, Rx) -Bupropion Hydrochloride (Rx) NRT Medications Use high enough dose Scheduled dosing better than PRN Can be combined with Bupropion Don t combine with Varenicline Can be combined with each other Have very few contraindications Have no drug-drug interactions 15

18 Dosing: < 10 cigs/day: 14 mg patch 10 cigs/day: 21 mg patch Length of Treatment: -Up to 12 weeks Pros: -Easy, good compliance -Continuous nicotine delivery -OTC Cons: -Slow onset of action -Skin reaction -Insomnia Nicotine Patch Dosing: 2mg < 25 cigarettes/day 4mg > 25 cigarettes/day Length of Treatment: 8-10 weeks Nicotine Gum Use: - Chew and park (Slow, buccal absorption) - Acidic foods absorption Pros: -Flexible dosing (every 1-2 hours, up to 24 pieces/day) -Keeps mouth busy -OTC Cons: -Need to use correctly (chew and park) -Nausea, Heartburn Mouth and throat burning Nicotine Lozenge Dosing: Based on Time To First Cigarette (TTFC) 4 mg if 30 mins TTFC 2mg > if 30 mins TTFC Length of Treatment: 12 weeks Use: -Allow to dissolve (Don t Chew but Suck like a hard candy.) Pros: -Flexible dosing (Up to 20 lozenges/ day) More discreet than gum -Keep mouth busy -OTC Cons: Need to use correctly (don t chew, suck) May cause insomnia, some nausea, hiccups, heartburn, coughing 16

19 Nicotine Nasal Spray Dosing: 1-2 doses per hour 1 does = 2 spays (1 spray/nostril) Use enough to control withdrawal symptoms Length of Treatment: 3-6 months weeks (PDR) Use: -Spray (don t sniff, swallow, or inhale) -PRN or fixed-schedule (1-2 doses/hour) Pros: -Rapid delivery though nasal mucosa -Flexible dosing (up to 40 doses) Cons: -Nasal irritation, rhinitis, coughing, & watering eyes. -Rx needed Non-Nicotine Pharmacotherapy First-line non-nrt medications FDA approved -Bupropion (Zyban/Wellbutrin) -Varenicline (Chantix) Others (nortriptyline, clonidine) Bupropion Hydrochloride Dopamine and norepinephrine (noradrenaline) effects Reduces cravings, withdrawal Improved abstinence rates in trials Less weight gain while using Start 7-10 days prior to quit date Continue 7-12 weeks or longer ( > 6 months) 17

20 Bupropion Precautions Contraindicated: seizure disorder, eating disorders, electrolyte abnormalities, MAO use OK with SSRIs NOT dangerous to smoke while taking Monitor blood pressure Side effects: Insomnia (40%) Dry mouth Headaches Rash Varenicline (Chantix) Action at 4 2 nicotine receptor Partial agonist/antagonist Releases lower amounts of dopamine into brain than smoke Reduces withdrawal Not as addictive as smoke Blocks nicotine from binding to receptor Prevents reward of smoking Varenicline (Chantix) In 2008 FDA added a warning regarding the use of varenicline noting that depressed mood, agitation, changes in behavior, suicidal ideation, & suicide have been reported in patients attempting to quit smoking while using varenicline. FDA recommends that: 1. Patients tell their healthcare provider about any history of psychiatric illness prior to starting this medication 2. Clinicians monitor patients for changes in mood and behavior when prescribing this medication 18

21 Electronic Cigarettes Introduced into US in 2007 Use has tripled among teens from No FDA regulations (yet) Can be purchased online No age restrictions Solvents used to dissolve nicotine are irritants and may be carcinogenic Companies don t disclose all ingredients of their electronic cigarette Electronic Cigarettes E-cigs vs. placebo helped with abstinence from smoking traditional cigs 30 days or less but not long term Surpasses all other forms of tobacco in youth population Flavors that might appeal to younger age group (chocolate, bubble gum ) Question # 4 Which of the following is the most commonly abused illicit drug in the US? A lorazepam B cannabinoids (marijuana) C opiates (heroin and pain medication) D alcohol E cocaine 19

22 Marijuana Marijuana Marijuana is the most commonly abused illicit drug in the United States Long-term marijuana abuse can lead to addiction; compulsive drug seeking and abuse despite its known harmful effects upon social functioning Long-term marijuana abusers trying to quit report irritability, sleeplessness, decreased appetite, anxiety, and drug craving, all of which make it difficult to quit Effect on Mental Health: Causes increased rates of anxiety, depress, SI, and schizophrenia. National Institute on Drug Abuse (NIDA) Website; Question # 5 An intoxicated patient is brought to the emergency department. Ocular examination reveals miosis. This patient was most likely using which of the following substances? (A) alcohol (B) cocaine (C) opioids (D) PCP (E) sedatives 20

23 Opiates Opiate Addiction Pharmacologic Interventions Opiate Agonists Methadone Partial Agonist, Partial agonist/antagonist buprenorphine buprenorphine/naloxone Antagonist Naltrexone (Vivtrol ) Why are opioid medications used to treat opioid addictions? Common myth is that all medications used to treat addictions are simply substituting one addiction for another Research has found that addiction to opioids results in significant changes in brain chemistry and function. Some of these changes may be permanent, meaning some individuals may require an opiate to bind to their changed receptors in order to function normally. Medication therapy significantly helps individuals stay in treatment more consistently, stay healthier, stay out of legal trouble, and generally function well in society. 21

24 Naltrexone (Vivitrol ) Naltrexone is a opiate antagonist Tightly blocks mu opioid receptors FDA approved for treating alcohol dependence and opiate dependence Decreases cravings in patients who abuse alcohol Comes in oral and IM depot formulations oral used to trial naltrexone prior to committing to IM IM- (Vivitrol ) depot formulation that is given monthly. If patients use opiates while on, no high. CAUTION: Will cause opiate withdrawal BLACK BOX WARNING-acute hepatic toxicity What is buprenorphine? Buprenorphine is a partial agonist of the mu opioid receptor Binds to and activates the receptor Partial agonists have a ceiling effect: larger doses do not produce greater highs-- has a very low risk of abuse and overdose. How does being a partial agonist safeguard against abuse? Features of Suboxone include: buprenorphine mixed with the antagonist naloxone (not in pregnancy) It must be taken correctly (dissolved under the tongue) to work correctly. If injected, the naloxone will bind to the receptors and put the person into rapid withdrawal. If it is swallowed without dissolving, there is no effect. When taken correctly, will act as an agonist and reduce craving and withdrawal symptoms. Once ceiling effect is achieved, other opioids such as heroin, are not able to bind to the receptors and therefore will produce no effects. If administered while using other opiates, it may act as an antagonist and put the person into immediate withdrawal. 22

25 References Creating Opportunities for Reducing Alcohol Related Harm in the Veteran Community; Session 6: Brief Intervention. Version 2.3. Department of Veterans Affairs, Australia. December 2002 < Thomas Babor, John Higgins-Biddle. Brief Intervention for Hazardous and Harmful Drinking-A Manual for Use in Primary Care. World Health Organization, Department of Mental Health and Substance Dependence Gentilello et al. Alcohol Interventions in a Trauma Center as a Means of Reducing Risk of Injury Recurrence. Annals Surgery 1999;230: National Survey on Drug Use and Health (NSDUH) sponsored by the U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA), Office of Applied Studies (OAS). National Institute on Drug Abuse (NIDA) Website; Gold, MS and Aronson, MD. Treatment of Alcohol Use and Dependence. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, Weinhouse, GL. Alcohol Withdrawal Syndromes. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, Motivational Interviewing: Resources for clinicians, researchers and trainers. Interaction Techniques. Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May American Academy of Family Physicians. Studies Suggest E-Cigarettes Don't Aid Long-term Smoking Cessation: American Family Physician. June