Update and Review of Medication Assisted Treatments for Opiate and Alcohol Use Disorders Richard N. Whitney, MD Medical Director Addiction Services Shepherd Hill Newark, Ohio Medication Assisted Treatment of Addiction Which patients? Which diagnoses? Which medication? How long? Fit in with program philosophy? Affordability? Prescribers in area? Proven efficacy? OK with 12 Step groups? How do I refer patients? Why is this Still a Controversial Subject in 2015??? This topic elicits strong negative reactions from many persons in recovery as well as treatment professionals with an anti medication bias. Many in the addiction treatment field as well as other medical fields suggest that using medications in the treatment of addictive disease is replacing one drug addiction with another. 1
Why is this Still a Controversial Subject in 2015??? How do we reconcile the incompatibility between the scientific literature which clearly documents the benefits of medication assisted therapies and the widespread resistance against appropriate pharmacotherapy among treatment professionals? Scientific evidence clearly demonstrates the short and, most importantly, the long term efficacy of medications used in the treatment of addictive disease, especially alcohol and opiate use disorders. Why is this Still a Controversial Subject in 2015??? Even in the face of increasingly serious national epidemics of opioid and alcohol use disorders, medication assisted therapies are underutilized. Studies have found that only about 30% of licensed addiction treatment programs offer any of the medications approved for opioid addiction, and only about 50% of potentially eligible patients within these program receive any of these medications. 18 Why is this Still a Controversial Subject in 2015??? Should we not strongly promote therapies which produce both favorable outcomes (abstinence, treatment compliance and retention, decreased medical and physical complications) as well as indirect benefits (reduced criminal behavior and legal involvement, family reunification, increased employment, improved physical health and overall quality of life)? 2
Addiction is a Brain Based Disease 3
Depression is a Brain Based Disease Anxiety is a Brain Based Disease 4
Schizophrenia is a Brain Based Disease Normal Brain Schizophrenic Brain 5
Abstinence Based Treatment Only? Would we recommend only non medication therapy for other serious brain based, life disruptive, potentially fatal illnesses like depression, severe anxiety and/or panic disorder, or schizophrenia? If so, would we do so in what we believe is the patient s best interests, or in our own best interest or because that is how we ourselves were treated? Would that recommendation change depending upon the longevity and severity of the patient s disease, or if our current treatment plan was not successful in alleviating the patient s symptoms? Opposition to Medication Assisted Therapy Implies rejection of disease model itself Substitution of one drug for another Drug free state is only valid treatment goal Substantial amounts of research have shown that this drug free state is neither achieved nor sustained by many heroin addicts, 4 and numerous studies support the efficacy of FDA approved medications in patients with alcohol use disorders. Substance Use Disorders Addiction to alcohol as well as to pharmaceutical opiates, heroin, and other opioid drugs, are nationally prominent problems producing significant suffering, substantial tragic and expanding levels of morbidity and mortality, as well as significant costs to society, especially in law enforcement and healthcare. 6
Substance Use Disorders Effective medications are available to treat alcohol and opiate addiction, but they are substantially underutilized. We in the addiction field need to evaluate the safety effectiveness of these medications, and recommend them appropriately to our patients with addictive disease. Medication Assisted Therapy for Alcohol Addiction Medications for Alcohol Addiction Antabuse (disulfiram) Naltrexone ReVia Vivitrol Campral (acamprosate) Anticonvulsants Other agents 7
Antabuse (disulfiram) FDA Approved Pharmacotherapies for Alcohol Dependence: Older Options Drug Class Disulfiram (Antabuse ) Naltrexone (ReVia ) Mini Profile Inhibits aldehyde dehydrogenase When taken with alcohol, [acetaldehyde] leads to nausea, dizziness, headache, flushing Decreases desire to drink Poor tolerability profile Black box warning, safety issues Opioid antagonist Binds to opioid receptors, thus blocking alcohol reward pathways Black box warning, safety issues 8
Disulfiram: Indications and Usage Patients with an alcohol use disorder who manifest significant problems in initiating or sustaining abstinence Those persons with addiction to alcohol who need a really good reason not to drink Persons who manifest alcohol abuse who really need to not drink (e.g.: hazardous occupations) Disulfiram: Indications and Usage Persons without alcohol use disorders but who wish to avoid high risk drinking Patientswithout a diagnosed alcohol use disorder for whom alcohol use in any amount serves as a trigger for relapse to their drug of choice Persons with co occurring cocaine dependence (??) Disulfiram: Mechanism of Action Inhibition of aldehyde dehydrogenase enzyme Alcohol then cannot proceed on its normal metabolic path to acetate Aldehyde builds up in a 1:1 response to the dose of ethanol presented Dose response phenomenon, so a trivial dose of EtOH (e.g.: inhaled fumes) results in a minor build up of acetaldehyde, and minor symptoms only 9
Disulfiram: Mechanism of Action A behavioral therapy more than a pharmacological therapy Effective but not always efficacious a patient has to swallow it for the medication to work Double blind studies show it s no better than placebo unless medication administration is monitored Disulfiram: Dosing 250 mg daily is most common dose Usually started 125 mg nightly for 4 8 nights Can give 500 mg three times weekly Monitoring of dosing is key! Aqueous suspension (250 mg/5 ml) can improve adherence (i.e., pill cannot be cheeked ) 10
Disulfiram: Adverse Effects Hepatotoxicity with long term treatment need to check liver function tests after initiating treatment May cause sedation, increase in depression or psychosis, cognitive impairment, i or worsening of dementia Metallic or garlic like taste or breath often reported Sensory neuropathy with long term therapy Disulfiram: Alcohol Reaction Hypotension, flushing, tachycardia, diaphoresis and dyspnea (shortness of breath) Severe headache, nausea, vomiting, abdominal pain, sulfur or garlic odor on breath Agitation, dysarthria (difficulty in speaking), chorea (abnormal involuntary movements) and lethargy Disulfiram: Therapeutic Approach May be used short term or long term May be used episodically, as for high risk circumstances (e.g., business trips, vacations) Optimal duration of use unclear Does not need to be tapered 11
Naltrexone: Oral Formulations (ReVia ) FDA Approved Pharmacotherapies for Alcohol Dependence: Other Options Drug Class Disulfiram (Antabuse ) Naltrexone (ReVia ) Mini Profile Inhibits aldehyde dehydrogenase When taken with alcohol, [acetaldehyde] leads to nausea, dizziness, headache, flushing Decreases desire to drink Poor tolerability profile Black box warning, safety issues Opioid antagonist Binds to opioid receptors, thus blocking alcohol reward pathways Black box warning, safety issues Naltrexone: Patient Selection Diagnosis of alcohol use disorder Strongly positive family history of AUD Strong subjective cravings for alcohol Strong subjective reward from alcohol An expressed desire to be in recovery and a willingness to engage in and complete treatment 12
Naltrexone: Contraindications Acute hepatitis or liver failure Persons on methadone maintenance therapy or buprenorphine maintenance therapy (due to opiate receptor blockade) Current or proximate need to be on opioid analgesic therapy (e.g.: upcoming major surgery) History of significant adverse effects or history of allergy to naltrexone Naltrexone: Purported Mechanism Competitive antagonist at mu opioid receptor Blocks endogenous opioid mediated release of dopamine in the nucleus accumbens in response to EtOH, thus blocking EtOH induced deuphoria Blunts rewarding effects of alcohol in humans Reduces subjective cravings and reduces return to heavy drinking 13