Overview of Medications to Treat Addiction in Primary Care

OVERVIEW OF
MEDICATIONS TO
TREAT ADDICTION IN
PRIMARY CARE

Prepared by
CASAColumbia®
February 2014

Outline
• Introduction

• Addiction Involving:
− Tobacco/Nicotine
− Alcohol
− Opioids
− Other Drugs
• Further Considerations
© CASAColumbia 2014

2

INTRODUCTION


3

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


4

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)

5

Stabilization
• Withdrawal in some cases can be lifethreatening
• 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


6

Addiction Treatment
• Treat addiction as a primary disease

• Address tobacco/nicotine, alcohol & other drugs
• Manage co-occurring disorders

dopamine
transporters


7

Combined Treatment
• Medications &
psychosocial therapies
• Can increase retention
in treatment

• Can decrease relapse
rates


8

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


9

Specialist Referral
Consider for Complex Cases
• Addiction medicine physicians
find a doctor near you
• Addiction psychiatrists
find a doctor near you

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


10

ADDICTION INVOLVING
TOBACCO/NICOTINE


11

FDA-Approved Meds
Tobacco/Nicotine
• varenicline (Chantix)
• bupropion (Zyban, Wellbutrin)
• nicotine replacement therapy
(e.g., patch, gum, lozenge,
inhaler, nasal spray)
• combinations
• combine with psychosocial therapies

12

varenicline
(Chantix)

• 3X higher odds of
smoking cessation7
• Nicotinic acetylcholine
receptor partial
agonist8
• Superior to bupropion
& single-form nicotine
replacement therapy9

13

varenicline
(Chantix)

• Begin 1wk prior to
target quit date
• Starting dose 0.5mg
QD x 3dy
• Up to 1mg BID x 12wk
extension of 12wk


14

varenicline
(Chantix)

• 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


15

bupropion
(Zyban, Wellbutrin)

• 2X higher odds of
smoking cessation11

• Inhibits
norepinephrine &
dopamine uptake12


16

bupropion
(Zyban, Wellbutrin)

• Begin 1wk prior to
target quit date
• Starting dose 150mg
QD x 3dy
• Up to 150mg BID
x 7-12wk extension
of 12wk


17

bupropion
(Zyban, Wellbutrin)

• 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

18

nicotine replacement
(Nicoderm, Nicorette, Commit, Nicotrol)

• 1.5X to 2X higher odds of smoking cessation13
• Nicotine without exposure to other toxins


19


• Contraindications: severe angina, postmyocardial infarction, pregnancy,
hypersensitivity
• Side Effects: minimal except nasal spray (local
irritation, cough, headache, dyspepsia)
• Combination long-acting (e.g., patch) & shortacting (e.g., gum) better than single form13


20


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


21


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

22

ADDICTION INVOLVING
ALCOHOL


23

FDA-Approved Meds
Alcohol
• acamprosate (Campral)
• disulfiram (Antabuse)
• naltrexone (ReVia, Depade,
Vivitrol)
• combine with psychosocial
therapies


24

acamprosate
(Campral)

• Improves abstinence
& treatment
retention14
• May modulate
glutamate & GABA15


25

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


26

disulfiram
(Antabuse)

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

27

disulfiram
(Antabuse)

• Causes diaphoresis,
headache, dyspnea,
hypotension, palpitations,
nausea, vomiting (when
using alcohol)
• Monitoring by spouse,
supervisor, etc. is highly
recommended

28

disulfiram
(Antabuse)

• 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

29

naltrexone
(ReVia, Depade, Vivitrol)

• Decreases drinking by
83% over placebo17
• FDA-approved for
alcohol or opioids
• Mu opioid receptor
inhibitor
• Genetic factors affect
efficacy

30

naltrexone

• 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


31

naltrexone

• 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


32

ADDICTION INVOLVING
OPIOIDS


33

FDA-Approved Meds
Opioids

• 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


34

buprenorphine/naloxone

• 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

35

buprenorphine/naloxone

• 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

36

methadone
(Methadose)

• Reduced use & better
treatment retention21
• Long-acting opioid
agonist
• Distributed only by
licensed facilities


37

methadone
(Methadose)

• 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


38

methadone
(Methadose)

• Contraindications: respiratory depression,
severe asthma, ileus, hypersensitivity
• Side Effects: QT prolongation, respiratory
depression


39

ADDICTION INVOLVING
OTHER DRUGS


40

FDA-Approved Meds
Other Drugs

• Currently no FDA-approved
medications for addiction
involving other drugs
• Research & development
ongoing for marijuana,
cocaine, others
• Combine with psychosocial
therapies

41

FURTHER CONSIDERATIONS


42

For Prescription Drugs
Always consider risks of
addiction if prescribing
• Opioids
• Benzodiazepines

• Stimulants
• Other addictive
prescription drugs


43

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

44

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)


45

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


46

References
11. 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.

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.
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.


47

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.


48

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