Overview of Medications to Treat Addiction in Primary Care

OVERVIEW OF MEDICATIONS TO

TREAT ADDICTION IN PRIMARY CARE

Prepared byCASAColumbia®

February 2014

Outline

• Introduction• Addiction Involving:

− Tobacco/Nicotine− Alcohol− Opioids− Other Drugs

• Further Considerations

INTRODUCTION

Addiction

For background information on addiction Addiction Medicine: Closing the Gap between Science and Practice1

Addiction

For information on screening, diagnosis, treatment planning & management

Overview of Addiction Medicine for Primary Care2 (62 Slides)

Overview of Addiction Medicine for Primary Care: Supplement3 (30 Pages)

Stabilization

• Withdrawal in some cases can be life-threatening

• Medical management for stabilization/detoxification may be required

• Details for these topics can be found on Pages 88-92 of the CASAColumbia® report Addiction Medicine: Closing the Gap between Science and Practice1

Addiction Treatment

• Treat addiction as a primary disease• Address tobacco/nicotine, alcohol & other drugs• Manage co-occurring disorders

dopamine transporters

Combined Treatment

• Medications & psychosocial therapies

• Can increase retention in treatment

• Can decrease relapse rates

Combined Treatment

• To achieve the best results medications should be combined with psychosocial therapies

• Research studies illustrate the effectiveness of various combinations of treatment4-6

• Details for psychosocial therapies can be found on Pages 102-106 of the CASAColumbia® report Addiction Medicine: Closing the Gap between Science and Practice1

Specialist Referral

• Addiction medicine physicians find a doctor near you

• Addiction psychiatrists find a doctor near you

Addiction medicine physician: http://www.abam.net/find-a-doctorAddiction psychiatrist: https://application.abpn.com/verifycert/verifyCert.asp?a=4

Consider for Complex Cases

ADDICTION INVOLVING TOBACCO/NICOTINE

FDA-Approved Meds

• varenicline (Chantix)• bupropion (Zyban, Wellbutrin)• nicotine replacement therapy (e.g., patch, gum, lozenge, inhaler, nasal spray)• combinations• combine with psychosocial therapies

Tobacco/Nicotine

varenicline(Chantix)

• 3X higher odds of smoking cessation7

• Nicotinic acetylcholine receptor partial agonist8

• Superior to bupropion & single-form nicotine replacement therapy9

• Begin 1wk prior to target quit date

• Starting dose 0.5mg QD x 3dy

• Up to 1mg BID x 12wk extension of 12wk

• Black Box Warning: neuropsychiatric events• Common Side Effects: headache, insomnia,

nausea, abnormal dreams• FDA Warning: increased risk of CV events in

patients with known CVD• Meta-analyses show no increased risk of

neuropsychiatric events9 or cardiac events9-10

bupropion(Zyban, Wellbutrin)

• 2X higher odds of smoking cessation11

• Inhibits norepinephrine & dopamine uptake12

• Begin 1wk prior to target quit date

• Starting dose 150mg QD x 3dy

• Up to 150mg BID x 7-12wk extension of 12wk

• Black Box Warning: neuropsychiatric events• Contraindications: seizure disorder /

predisposition; abrupt cessation of alcohol / sedatives; risky use / addiction involving alcohol

• Common Side Effects: insomnia, tachycardia, weight loss, headache, lower seizure threshold

• Meta-analysis shows no increased risk of neuropsychiatric events9

nicotine replacement(Nicoderm, Nicorette, Commit, Nicotrol)

• 1.5X to 2X higher odds of smoking cessation13

• Nicotine without exposure to other toxins

• Contraindications: severe angina, post-myocardial infarction, pregnancy, hypersensitivity

• Side Effects: minimal except nasal spray (local irritation, cough, headache, dyspepsia)

• Combination long-acting (e.g., patch) & short-acting (e.g., gum) better than single form13

Dosing for 1 cigarette 1mg of nicotine• Patch (OTC): 7/14/21mg, q12-24hr, 8wk taper• Gum (OTC): 2/4mg, q1-2hr, 3mo taper• Lozenge (OTC): 2/4mg, q1-2hr, 3mo taper• Inhaler (Rx): 6-16 cartridges, q24hr, 3-6mo taper• Nasal Spray (Rx): 1-2 sprays, q1hr, 3-6mo taper

Delivery method characteristics• Patch (OTC): only long-acting method• Gum (OTC): “chew & park” technique crucial;

should not be used with acidic food or liquids• Inhaler (Rx): beneficial for behavioral rituals• Nasal Spray (Rx): fastest absorption, most side

effects

ADDICTION INVOLVING ALCOHOL

FDA-Approved Meds

• acamprosate (Campral)• disulfiram (Antabuse)• naltrexone (ReVia, Depade,

Vivitrol)• combine with

psychosocial therapies

Alcohol

acamprosate(Campral)

• Improves abstinence & treatment retention14

• May modulate glutamate & GABA15

acamprosate(Campral)

• Begin once abstinent for >24hr if possible• Dose at 666mg TID x 6mo• Safe even with severe hepatic disease• Contraindication: severe renal disease• Common Side Effects: diarrhea, fatigue

disulfiram(Antabuse)

• Best efficacy with routine use in monitored systems given high rates of noncompliance16

• Aldehyde dehydrogenase inhibitor

• Causes diaphoresis, headache, dyspnea, hypotension, palpitations, nausea, vomiting (when using alcohol)

• Monitoring by spouse, supervisor, etc. is highly recommended

• Starting dose: 250-500mg QD x 1-2wk• Maintenance dose: 125-500mg QD x 6mo• Clinicians often start & maintain at 250mg QD• Remains active 14 days after discontinuation• Contraindications: severe myocardial occlusive

disease, psychosis, hypersensitivity• Side Effects: hepatitis, psychosis

naltrexone(ReVia, Depade, Vivitrol)

• Decreases drinking by 83% over placebo17

• FDA-approved for alcohol or opioids

• Mu opioid receptor inhibitor

• Genetic factors affect efficacy

• Only begin after abstinence from opioids >7dy• Starting oral dose

25mg QD (Day 1), 50mg QD (Day 2)• Maintenance oral dose 50mg QD x 6mo• Depot dose 380mg IM q4wk: better compliance• Trial of at least 3mo recommended

• Black Box Warning: hepatotoxicity• Contraindications: acute hepatitis, liver failure,

prescribed opioids• Side Effects: headache, GI distress, syncope,

LFT elevation• Literature review suggests no increased risk for

causing or worsening hepatic disease18-19

ADDICTION INVOLVING OPIOIDS

FDA-Approved MedsOpioids

• buprenorphine/naloxone (Subutex, Suboxone, Zubsolv)

• methadone (Methadose)• naltrexone (ReVia, Depade,

Vivitrol)*• combine with

psychosocial therapies* details for naltrexone included on previous slides for addiction involving alcohol

buprenorphine/naloxone(Subutex, Suboxone, Zubsolv)

• Reduced use & better treatment retention20

• Partial opioid agonist + opioid antagonist• Exercise caution in quantities prescribed per

visit due to potential for misuse• Special training required in order to prescribe• See details under section “For Physicians” at

buprenorphine.samhsa.gov

buprenorphine/naloxone(Subutex, Suboxone, Zubsolv)

• Starting dose

8mg QD (Day 1)16mg QD (Day 2-3)

• Maintenance dose 12-16mg QD• Contraindication: hypersensitivity• Side Effects: respiratory

depression, headache, pain, insomnia, GI symptoms

methadone(Methadose)

• Reduced use & better treatment retention21

• Long-acting opioid agonist

• Distributed only by licensed facilities

• Starting dose 20-40mg QD• Maintenance dose 80-120mg QD• Dose may be less depending on baseline opioid

use• Must follow licensed facility protocol, e.g., EKGs

• Contraindications: respiratory depression, severe asthma, ileus, hypersensitivity

• Side Effects: QT prolongation, respiratory depression

ADDICTION INVOLVING OTHER DRUGS

FDA-Approved MedsOther Drugs

• Currently no FDA-approved medications for addiction involving other drugs

• Research & development ongoing for marijuana, cocaine, others

• Combine with psychosocial therapies

FURTHER CONSIDERATIONS

For Prescription Drugs

Always consider risks of addiction if prescribing• Opioids• Benzodiazepines• Stimulants• Other addictive

prescription drugs

For Adolescent Patients

• Only buprenorphine/naloxone is FDA-approved for 16 years & older

• All other medications are FDA-approved for 18 years & older

• Adolescent treatment should focus more on psychosocial therapies

For Elderly Patients

• Monitor for drug-drug interactions• For renal insufficiency adjust dosing of

varenicline, bupropion, acamprosate, methadone

• For hepatic insufficiency adjust dosing of bupropion, buprenorphine/naloxone, methadone, naltrexone (contraindication if severe)

References1. CASAColumbia. Addiction medicine: closing the gap between science and practice. 2012 Jun. http://

www.casacolumbia.org/addiction-research/reports/addiction-medicine

2. CASAColumbia. Addiction medicine: primary care clinical guide. 2013 Aug. http://www.casacolumbia.org/health-care-providers/guide

3. CASAColumbia. Addiction medicine: primary care clinical guide supplement. 2013 Aug. http://www.casacolumbia.org/health-care-providers/guide-supplement

4. Amato L, et al. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD005031.

5. Anton RF, et al. Naltrexone combined with either cognitive behavioral or motivational enhancement therapy for alcohol dependence. J Clin Psychopharmacol. 2005 Aug;25(4):349-57.

6. Feeney GF, et al. Cognitive behavioural therapy combined with the relapse-prevention medication acamprosate: are short-term treatment outcomes for alcohol dependence improved? Aust N Z J Psychiatry. 2002 Oct;36(5):622-8.

7. Fiore MC, et al. Clinical practice guideline. Treating tobacco use and dependence: 2008 update. U.S. Department of Health and Human Services, 2008 May.

8. U.S. Food and Drug Administration. Highlights of prescribing information for Chantix (varenicline). 2013 Feb. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021928s030lbl.pdf

9. Cahill K, et al. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013 May 31;5:CD009329.

10. Prochaska JJ, et al. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ 2012; 344:e2856.

References11. Hughes JR, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000031.

12. U.S. Food and Drug Administration. Prescribing information: Zyban (bupropion hydrochloride). 2012 Jan. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020711s036lbl.pdf

13. Stead LF, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012 Nov 14;11:CD000146.

14. Rösner S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004332.

15. U.S. Food and Drug Administration. Highlights of prescribing information for Campral (acamprosate calcium). 2012 Jan. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021431s015lbl.pdf

16. Laaksonen E, et al. A randomized, multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence. Alcohol Alcohol. 2008 Jan-Feb;43(1):53-61.

17. Rösner S, et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD001867.

18. Brewer C, et al. Naltrexone: report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literature. Addict Biol. 2004 Mar;9(1):81-7.

19. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Naltrexone: LiverTox Clinical and Research Information on Drug-Induced Liver Injury. http://livertox.nih.gov/Naltrexone.htm

20. Mattick RP, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD002207.

21. Mattick RP, et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD002209.

Acknowledgements

• Margot Cohen contributed much of the research and writing for these materials.

• The following subject-matter experts served as external reviewers for these materials: Kevin Kunz, M.D., M.P.H., Frances Levin, M.D., Charles O’Brien, M.D., Ph.D.

• Funding was provided by The Joseph A. Califano, Jr. Institute for Applied Policy.

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