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Treatment of Opioid Use Disorder

Sarah Wakeman, MD, FASAM Medical Director,

Mass General Substance Use Disorder Initiative Assistant Professor, Harvard Medical School

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Disclosures

Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest

to disclose.

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Components of Treatment for Opioid use Disorder

Pharmacotherapy

• Full opioid agonist: methadone

• Partial opioid agonist: buprenorphine

• Opioid antagonist: naltrexone

Psychosocial/behavioral

• Levels of care – Outpatient, IOP/PHP,

residential

• Modalities – CBT, MI/MET, CM, TSF

Peer-based Recovery Support

• AA, NA, SMART recovery

• Recovery coaches

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Similar to Management of Diabetes

• No cure

• Goal is euglycemia and prevention of acute and chronic complications

• Individualized treatment plans and targets

• Treatment includes: – Medication

– Lifestyle changes

– Regular monitoring for complications

– Behavioral support

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Pharmacology of Treatments

Antagonist (naltrexone)

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Details of Treatment

• Agonist treatment consists of daily methadone or buprenorphine – Stable level of opioid effect is experienced as neither

intoxication nor withdrawal, but as “normal” – Requires waivered prescriber or opioid treatment program

• The aims of agonist maintenance treatment include: – reduction or cessation of illicit opioids and associated risks – improvement in psychological and physical health

• Antagonist treatment consists of once monthly injection – Anyone can prescribe naltrexone

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Detoxification versus Maintenance

• Pharmacological management: – tapering with methadone or buprenorphine

– sudden opioid cessation and use of alpha-2 adrenergic agonists to relieve symptoms

• Most patients resume opioid use within six months of detoxification

• Detoxification alone should not be promoted as effective treatment

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Behavioral Treatments

• Evidence-based interventions either skills-based or utilize incentives

• Goal to engage people in treatment, change attitudes and behaviors related to substance use, and increase skills to manage stress & cravings

• Cognitive-behavioral therapy: – skills to manage cravings, identify and avoid high risk situations, utilize

self-monitoring

• Motivational Enhancement Therapy: – resolve ambivalence through eliciting reasons for change,

strengthening motivation, and developing a plan for change

• Contingency Management: – rewards for engaging in treatment or not using substances

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Opioid Agonist Treatment Saves Lives

Maryland: 50% reduction in overdose death with opioid agonist treatment

France: 79% reduction in overdose death opioid agonist treatment

Schwartz RP et al. Am J Public Health. 2013 May;103(5):917-22 Carrieri MP et al. Clin Infect Dis. 2006 Dec 15;43 Suppl 4:S197-215

www.mghcme.org Kimber J et al. BMJ 2010;341:bmj.c3172

25% of patients never on agonist tx will be dead within 25 years vs 6% of those with 5+ yrs of cumulative agonist tx

Opioid Agonist Treatment Saves Lives

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Opioid Agonist Therapy Reduces Recurrence

Clark RE et al. J Subst Abuse Treat. 2015 Oct;57:75-80

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Most Patients Achieve Remission

Weiss et al. Drug Alc Depend. 2015;150:112-9.

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Hser et al. Addiction. 2016 Apr;111(4):695-705.

Early Use During Treatment Expected

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Treatment Must Be Ongoing

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Kakko et al. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in

Sweden: a randomised, placebo-controlled trial. The Lancet, Volume 361, Issue 9358, 2003, 662 - 668

Poor Outcomes Without Maintenance

Treatment group: •Highly significant ASI reduction •75% negative tox screens •75% retained in treatment •No deaths

Control group: •0% retained in treatment •20% died

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Relapse Common After Taper

Sigmon et al. JAMA Psychiatry. 2013;70(12):1347-1354.

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Hospitalized patients

• Initiating methadone in hospital:

– 82% present for follow-up addiction care

• Initiating buprenorphine vs detox:

– Bupe: 72.2% enter into treatment after discharge

– Detox : 11.9% enter treatment after discharge

J Gen Intern Med. Aug 2010; 25(8): 803–808; JAMA Intern Med 2014 Aug;174(8):1369-76.)

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Treatment in the ER

• 78% vs 37% engaged in buprenorphine treatment

• Fewer days of self-reported opioid use

D'Onofrio et al. JAMA 2015 Apr 28;313(16):1636-44

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Treatment in Primary Care

No difference in self reported opioid use, opioid abstinence, study completion, or cocaine abstinence between the 2 groups

Fiellin DA et al. Am J Med 126:1 2013

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Extended Release Naltrexone

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•61% received all six injections •Strict selection criteria, paid $385-820 •Time to relapse significantly longer in NTX group:

•10.5 weeks versus 5.0 weeks (P<0.001)

•Relapse in 43% NTX vs 64% controls (P<0.001) •No difference between groups after treatment completion

N Engl J Med 2016; 374:1232-1242

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Agonist versus Antagonist Treatment

• Oral naltrexone ineffective

• Extended-release naltrexone more effective than placebo

• No direct comparisons between extended-release naltrexone and methadone or buprenorphine

• Retention rates worse with naltrexone

Bart G. J Addict Dis. 2012;31(3):207-25.

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Compulsory Residential Treatment vs Voluntary Methadone Maintenance:

Median Time to Relapse 31 vs 352 days

Wegman MP et al. Lancet Glob Health 2016

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Incentives Increase Naltrexone Adherence

• Contingency group: 43% increase in adherence; 10% -14% increase in opioid-negative urine samples

• Two-thirds of scheduled doses were not taken when incentives for adherence were not provided

Jarvis BP et al. Addiction, 2016

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Buprenorphine Implant Non-inferior

• Responders:

– 96.4% receiving buprenorphine implants

– 87.6% receiving sublingual buprenorphine

• 85.7% receiving implants and 71.9% receiving sublingual maintained opioid abstinence

Rosenthal et al. JAMA. 2016;316(3):282-290

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Buprenorphine Injection

SC injection, 28 day sustained release, variable dosing

Nasser AF et al. J Clin Psychopharmacol 2016;36: 18–26

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You Need a Pulse to Get Into Recovery!

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WHO Guidelines

• “Of all the treatments, opioid agonist maintenance treatment, combined with psychosocial assistance is most effective… psychosocial services should be made available to all patients, although those who do not take up the offer should not be denied effective pharmacological treatment.”

http://www.who.int/substance_abuse/publications/opioid_dependence_guidelines.pdf

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Thank you!

• @DrSarahWakeman

• swakeman@partners.org