Treatment ofOpioid Use Disorders

Chief Clinical Officer Clinical Professor of PsychiatryGeorgetown University School of

MedicineUniversity of Maryland School of

Medicine

George Kolodner, M.D.

Opioid Terminology

• Opiates: naturally occurring in opium poppy (morphine, codeine)

• *Opioids: broader term includes naturally occurring plus synthetics (heroin, methadone, oxycodone)

• Narcotics: legal term, includes cocaine

Paradox: Relatively Harmless But Lethal

• Not tissue toxic– Compare to alcohol and tobacco– Infectious diseases linked to non-sterile needles– Malnutrition linked to dietary neglect

• Acute death by overdose– Downregulation of receptors during periods of

abstinence lead to re-sensitizing of CNS respiratory centers in brain stem

Opioid Cautions and Reassurances

• 400 BC. Hippocrates: “Use sparingly”

• 1853. Hypodermic syringe– “Decrease addiction by avoiding stomach”

• 1898. Bayer Heroin– “Less addictive than morphine for coughs”

– Compare to Bayer Aspirin

19th C. Opioid Medication Epidemic

• 1870s – 80s: Overuse of hypodermic injection by physicians

• 1890’s – 1910s: Change to more balanced prescribing patterns through education and pressure by reform minded physicians and pharmacists

– NEJM 373:22, 2095-7, 2015. David Courtwright, Preventing and Treating Narcotic Addiction

Criminalization of Opioid Addiction

• 1915: Harrison Narcotic Act was intended to keep narcotic transactions within legitimate medical channels

– Actually implemented by Treasury Department in a way that interfered with treatment of addiction

• The treatment of addiction is “outside the realm of legitimate medical interest.”

– Webb et al vs. United States, 1919

Legal to treat pain with opioids but not the addiction which sometimes developed

Opioid Related Overdose Deaths United States, 1999-2013

Death Rates by Age Group from Overdoses of Heroin or Prescription Opioid Pain Relievers (OPR)

SOURCE: CDC. Increases in Heroin Overdose Deaths — 28 States, 2010 to 2012

MMWR. 2014, 63:849-854

Rates of Opioid Sales & OD Deaths1999–2013

0

1

2

3

4

5

6

7

8

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Source: National Vital Statistics System, DEA’s Automation of Reports and Consolidated Orders System

Government Responses

• 2007: FDA given broader powers by Congress to deal with “epidemic” of opioid prescribing– Risk Evaluation and Mitigation Strategies

(“REMS”)

• 2015: Maryland Board of Physicians mandate for one hour of CME per renewal cycle

• 2016: Center for Disease Control CDC Guidelines for Prescribing Opioids for Chronic Pain

Risk Evaluation and Mitigation Strategies (“REMS”)

• Refers to a variety of measures, beyond traditional package labeling, that the FDA can take to minimize the risks of a particular medication

• Major focus has been on extended release, long acting (ER/LA) opioids

– Development of new formulations to reduce diversion

– Education of prescribing physicians

CDC Guidelines: Prescription of Opioid Medications for Chronic Pain (January, 2016)

1. Non-pharmacologic and non-opioid pharmacologic therapies are preferred

2. Before starting, discuss risks and benefits, reasonable goals for pain and functioning, and have plan for discontinuation

3. Begin with immediate-release instead of extended-release/long-acting (ER/LA) opioids

4. Periodically reevaluate and work to lower dose or discontinue

CDC Guidelines: Prescription of Opioid Medications for Chronic Pain (January, 2016)

5. Use urine testing before starting and periodically thereafter

6. Use Prescription Drug Monitoring Program (PDMP)

7. Avoid using opioids for patients taking benzodiazepine medication

8. Screen for history of substance use disorder

Confusion Between “Physical Dependence” and “Addiction”

• To try reduce confusion, diagnostic terminology was changed in DSM-5 from:

• “Opioid (etc.) Dependence/Abuse” to

• “Opioid (etc.) Use Disorder”

• “Abuse” = “Mild”

• “Dependence” = “Moderate or Severe”

Physical Dependence

• Onset of withdrawal symptoms upon the cessation of a substance

– Unmasks neuro-adaptations that have occurred in response to use of substance

• Neurobiology

– Locus coeruleus (noradrenergic)

Irritability, increased heart rate and BP, hyperalgesia

– Reward centers (dopaminergic)

Anhedonia, depression

Operational Diagnosis of Addiction

• Continued use of psychoactive substances despite a pattern of adverse consequences

– Substance use is under poor control and increases in volume

– The substance occupies a central place in the person’s life and leads to behavior that is out of character and violates the person’s usual values

• Diagnosis is based on the consequences of using – not on the amount or frequency

32

2317 15

11 9 95 4

Percentage of Substance Users Who Become Addicted, by Substance

Change in Substance Use by Kolmac Patients

1989 2016

Cocaine 44% 9%

Opioids 6% 31%

Marijuana 6% 17%

Benzodiazepines

2% 8%

Treatment of Opioid Use Disorders

• Withdrawal management is needed more frequently than with substances other than tobacco

• “Abstinence-based” treatment has been less successful than for other substances

• Controversy about the balance between therapy and medication

• Controversy about the role of agonist and antagonist medication

Agonists and Antagonists

• Full agonist: attaches to opioid receptor and fullyactivates it

– Opium, morphine, codeine, oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), methadone

• Antagonist: attaches to opioid receptor and blocks it instead of activating it

– Naltrexone (Revia, Vivitrol)

• Partial agonist: attaches to opioid receptor, partially activates and blocks it

– Buprenorphine (Suboxone)

Antagonists

• Naloxone (“Narcan”)

– Reverses opioid overdose

– Immediate effect with short duration

– Injectable or nasal

• Naltrexone

– Used for relapse prevention

– Used long term (months to years)

– Formulations

• Oral (“Revia”)

• Depot injection lasts for 1 month (“Vivitrol”)

Opioids For Addiction Treatment:A Change of Approach

• Methadone– 1937. Developed in Germany for pain

– 1971. Approved in USA for detoxification and maintenance of opioid addicts

– Highly restricted use – regulated programs (OTP)

– Now taken by about 250,000 patients in US

• Buprenorphine– 1978. Parenteral formulation for pain

– 2000 – 2003. Approval for addiction treatment

– Available for office based use by “waivered” prescribers• Initially only physicians but now also NPs and PAs

– Now taken by about 1,000,000 patients in US

Buprenorphine FDA ApprovalDEA Schedule III

• For pain

– Parenteral (Buprenex)

– Transdermal (Butrans)

• For addiction (buprenorphine waiver and DEA “X” number required)

– Sublingual (Suboxone, Zubsolv, generic)

– Buccal (Bunavail)

Advantages of Buprenorphine

1. Safer from overdose

– Ceiling on respiratory depression

• Benzodiazepines raise ceiling

2. Rarely causes euphoria unless taken IV

– Partial mu agonist

3. Blocks most other opioids

– High affinity for receptor sites

4. Can eliminate all withdrawal symptoms including craving

Experience with Buprenorphine at Kolmac

• Compared to naltrexone

– Doubling of completion rate in rehabilitation phase

• No reduction in completion rate of non-opioid patients

– Substantial participation in continuing care phase

– Reduction in overdose deaths

• Improves the patient’s ability to do the psychological work of recovery

– Ancillary not curative

Buprenorphine vs. Methadonein Pregnancy

• Same incidence of neonatal abstinence syndrome (NAS)

• Less severe NAS with buprenorphine– 89 % less medication

– 43% fewer hospital days

• More discontinuation of buprenorphine than methadone because of dissatisfaction with medication

• Methadone still the official standard of care

Resistance to MAT in Recovery Community

• Narcotics Anonymous

• 12-Step based residential rehabilitation programs

• Hazelden/Betty Ford Breaking ranks

• Forcing redefinition of “recovery”

– William White: www.williamwhitepapers.com

Modern Addiction Recovery

kolmac.com/category/articles

Send requests for addiction topics to:

gkolodner@kolmac.com

Thank You!