Drugs for Treating Drug Addiction by Barry Zevin MD

1. Drugs For Treating Drug Addiction Barry Zevin MD Tom Waddell Health Center San Francisco Department of Public Health Homeless Programs Board Certified Internal Medicine Board Certified Addiction Medicine Barry_Zevin@sfdph.org

2. Disclosures And Disclaimer • Barry Zevin accepts no payments, samples, or gifts from any pharmaceutical companies • The opinions expressed here are those of the presenter • All information regarding medications expressed here should be checked out!

3. Drugs for Treating Drug Addiction? • What’s the difference between a drug and a medication anyway? • If a medication could treat addiction, how would we know it was working? • Why have the results of this been “disappointing” so far? Disappointing to who?

4. 3 Flavors of Outcomes • Traditional Abstinence Paradigm • Neurobiology of Addiction Paradigm • Harm Reduction Paradigm

5. What Would an Effective Medication Look Like From a Harm Reduction Point of View?

6. What is FDA Approved For Treating Addiction? • Tobacco: nicotine replacement, bupropion, verenicline • Alcohol: chlordiazapoxide (specific regimen for withdrawal), diazapam (specific regimen regimen for withdrawal), oxazapam (specific regimen regimen for withdrawal), disulfiram, acamprosate, naltrexone • Opioids – heroin: naltrexone, methadone only in NTP, buprenorphine • Opioids – prescription opioids: naltrexone, methadone only in NTP, buprenorphine • Stimulants – methamphetamine: none • Stimulants – cocaine: none • Benzodiazepine, carisoprodol, GHB, Other sedative-hypnotics: none • Marijuana: none • Process Addictions – gambling, porno, shopping, etc.: none

7. FDA Approved For Indications Other Than Addiction • Tobacco: clonidine, nortryptaline • Alcohol: benzodiazepines, topiramate, ondansetron, valproate, other aeds, baclofen, • Opioids – heroin: clonidine, other prescription opioids • Opioids – prescription opioids: clonidine, other prescription opioids • Stimulants – methamphetamine: baclofen, other psychostimulants, mirtazapine, bupropion, venlafaxine, topiramate, other aeds • Stimulants – cocaine: baclofen, naltrexone, topiramate, other aeds • Marijuana: gabapentin, pregabalin • Process Addictions – gambling, porno, shopping, etc.: naltrexone

8. Other Non FDA Approved Substances Used to Treat Addiction • Tobacco: Herbs (lobelia, St. Johns wort, oat straw, valerian, ginseng) • Alcohol: cannabis • Opioids – heroin: heroin, ibogaine • Opioids – prescription opioids: ibogaine • Stimulants – methamphetamine: cannabis • Stimulants – cocaine: cannabis • Marijuana: ? • Process Addictions – gambling, porno, shopping, etc.: ?

9. Relevant Outcomes • Safe / comfortable withdrawal • Abstinence / relapse prevention • Controlled use • Reduced heavy use / Less using days / Less use overall • Reduce harm related to mode of use, impurity of substance • Prevent overdose • Better mental health • Better quality of life • Reduce mortality • Retention in treatment • Reduce craving • Anti-depressant • Better cognition / Maintain cognitive function • Reset tolerance • Turn on or off effects of drug as needed • Reduce criminal activity

10. What Works? • Good evidence • Scientific study • Experience of practitioners and patients • Relevant outcomes • Reasonable safety – benefits outweigh adverse effects • Acceptability to patients • Acceptable cost for benefit • Conversely what doesn’t work is defined by absence of evidence, irrelevant outcomes, risk, and lack of acceptability to potential patients, unavailable due to high cost

11. What Works? • BZD treatment of alcohol withdrawal • Thiamine to prevent WKS • Treatment of co-occurring mental health disorders – esp. if treatment adds additional / symptomatic benefits and has reasonable safety and acceptability • Depression treatment • Psychosis treatment • ADHD treatment • Anxiety disorders

12. What Works? • Naloxone to reverse opioid overdose • Buprenorphine, methadone maintenance to treat opioid dependence • Nicotine replacement with gradual tapering to treat tobacco dependence • Nicotine patch plus short acting nicotine • Nicotine replacement to reduce smoking even in people not ready to quit • Bupropion or nortryptaline to treat tobacco dependence • Varenicline to treat tobacco dependence

13. What’s Worth Trying? Less Evidence / Less Relevant Outcomes / Higher Risk / Less Acceptability • Placebo for any indication • Cannabis to treat various addictions • Alcohol • Baclofen, various aed’s to treat alcohol withdrawal • Naltrexone for alcohol dependence • Disulfiram for alcohol dependence when there is strong family or other support for witnessed dosing • Acamprosate for alcohol dependence • Ondansetron for alcohol dependence esp in strong family history / early onset drinkers • Tobacco • Nicotine replacement used indefinitely • Verenicline for patients with underlying mental health disorders (in patients who can be followed up closely)

14. What’s Worth Trying? Less Evidence / Less Relevant Outcomes / Higher Risk / Less Acceptability • Opioids • Clonidine for Opioid withdrawal (along with various other symptomatic medications) • Naltrexone for opioid dependence (in “highly motivated”?) • Stimulants • Baclofen for cocaine or methamphetamine dependence (esp if chronic pain / muscle spasm) • Psycho-stimulants for stimulant dependence in the absence of ADHD • Disulfiram for cocaine dependence esp in alcohol drinkers who are willing to stop (not for actively drinking unable / unwilling to stop) • Process addictions • Naltrexone

15. What Doesn’t Work? • Anti-depressants for stimulant dependence when depression is not present • Dopamine agonists (egbromocriptine, amantadine, pergolide) or most aed’s for stimulant dependence • Disulfiram for alcohol dependence in settings in which daily dosing cannot be assured • Naltrexone for opioid dependence in “less motivated” patients • SSRI’s in type II (early onset – strong family history) alcoholism • Worse outcomes than placebo • Ultra-rapid opioid detox

16. Thank You to All My Colleagues at Tom Waddell Health Center and Our Many Partners Thank You to My Patients Who I Learn From Every Day