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Medication Assisted Treatment

for Opioid Epidemic

Dealing with the Opioid Epidemic -

A Training Resource

By Jim Messina, Ph.D., CCMHC, NCC, DCMHS-T

Medications Used to Treat Opioid Addiction

 

Should medications be used in the treatment of addiction?

  • Is this a scientific question?
  • Is this a philosophical question?
  • Is this a practical question?

 

Rationale for medication

  • Impact the physiology of addiction and dependence
  • Improve outcomes including retention and opioiduse
  • Protect against lapses, which should be expected
  • Reduce high rates of relapse
    • Without medications >80% of heroin addicts relapse within 30 days after detoxification

 

Medications for the treatment of opioid addiction

  1. Methadone – Full Agonist (See Note below) of Opioids
  2. Buprenorphine(bupe) - Partial Agonist of Opioids - suboxone, subutex, zubsolv, bunavail
  3. Extended release Naltrexone(XRNTX) – Antagonist of Opioids - Vivitrol

For Overdoses

  1. Naloxone - Narcan

NOTE: An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist.
Document
XR-Naltrexone: A Step-by-Step Guide (2017)

CDC recommendations for prescribing opioids for chronic pain outside of active cancer, palliative, and end-of-life care

 

Determining When to Initiate or Continue Opioids for Chronic Pain

1.Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate.

2.Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and should consider how therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety.

3.Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy.

 

Opioid Selection, Dosage, Duration, Follow-Up, and Discontinuation

1.When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids.

2.When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when increasing dosage to ≥50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to ≥90 MME/day.

3.Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than seven days will rarely be needed.

4.Clinicians should evaluate benefits and harms with patients within 1 to 4 weeks of starting opioid therapy for chronic pain or of dose escalation. Clinicians should evaluate benefits and harms of continued therapy with patients every 3 months or more frequently. If benefits do not outweigh harms of continued opioid therapy, clinicians should optimize other therapies and work with patients to taper opioids to lower dosages or to taper and discontinue opioids.

 

Assessing Risk and Addressing Harms of Opioid Use

1.Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder, higher opioid dosages (≥50 MME/day), or concurrent benzodiazepine use, are present.

2.Clinicians should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose. Clinicians should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

3.When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.

4.Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible.

5.Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

 
Document
CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016


Effectiveness of medications for opioid addiction

Methadone

–Multiple clinical trials and meta-analyses (e.g. Cochrane)

 Below 50% have 6-month abstinence retention

 

Buprenorphine

–Multiple clinical trials and meta-analyses (e.g.Cochrane)

50% have 6-month abstinence retention

 

Naltrexone

–Limited effectiveness in pill form

–Long acting injections and implants produce around 50% retention and sustained abstinence (e.g. Krupitskyet al., 2011)

 

Relapse prevention medications Improve outcomes

Reduced Drug use

Reduced Mortality

Reduced Criminal behavior and recidivism

Reduced HIV and HCV transmission

Reduced Hospitalization

Reduced Homelessness

Reduced Psychiatric symptoms

Increased Employment

Increased Treatment retention

Decreased Downstream costs

 

Choice of medication: Methadone vs Buprenophine vs XR-NTX (extended release naltrexone)

Patient preference and family preference

Failure of other treatments, try something new

Side effects, anxious anticipation

Long acting duration of XRNTX

Methadone and bupe intrinsically reinforcing

Methadone and bupe relieve withdrawal early

All 3 relieve cravings

More familiarity with methadone and bupe, positive and negative reputation

Partial blockade for bupe, full blockade for XRNTX

Strong opioid effects for methadone, pros and cons

Problems with acceptability of agonists

More tools in the toolbox

 

Duration of treatment?

Is there an optimal duration?

Evidence so far suggests longer is better, but care should be individualized

Retention under real world conditions is problematic

No reason to suppose pre-imposed limitations helpful

 

Relapse prevention medication Is the standard of care

But not everyone knows it yet

Persuading patients

Persuading families

Persuading criminal justice system

Persuading SUD providers, especially residential treatment

Persuading payers

Persuading the recovery community

 

A house divided

Why do we have philosophy in our field?

Big tent, all recovery voices matter

Treatment choice selection bias

Follow up observational bias

 

The power of language

“Drug-free” treatment

“Abstinence-based” treatment

Medication assisted treatment

Medication assisted recovery

Counseling-assisted medication

“Harm reduction”

Relapse-prevention medications

Anti-addiction medications

Is relapse prevention Medication Prescription just trading one addiction for another?

 

DSM Criteria for Substance Dependence

A maladaptive pattern of use leading to clinically significant impairment or distress, manifested by 3 or >of the following in a 12-month period:

1.  Tolerance (increased amounts or diminished effects)

2.  Withdrawal (withdrawal syndrome or use to relieve or avoid withdrawal) (Addictive Behaviors –loss of control)

3.  Efforts or desire to cut down or control use

4.  Taken Larger amounts or over a Longer period than intended

5.  Social, recreational or occupational activities given up

6.  Time spent in activities necessary to obtain the substance

7.  Use despite Persistent or recurrent Physical or Psychological problems  


Why medication? Can you be in recovery on medicines

1. Medicines just a crutch or band-aid

–Maybe. Like meetings or groups.

2. If the patients like it so much, there must be something wrong with it.

–But if they don’t utilize treatment, it almost doesn’t matter how good it is.

3. If medications are an “easy fix” will patients refuse needed psychosocial treatments and supports.

–Actually, they come to psychosocial treatment more.

4. If medications eliminate cravings will patients miss opportunity for needed cravings management?

–Academic if they relapse. Postpone until later when stronger. Remains an open question -maybe need high intensity skill building later in treatment course.

5. Abuse and diversion

–Real issue, needs to be managed, but not as problematic as scare stories make it out to be.

6. What about spiritual recovery instead of medicines?

–Why not both?

Limitations and unintended consequences Medications

Medication diversion

Inconsistency

Non-compliance

Dropout

Substandard practice

Side effects

Over-promising

Other substances

 

Additional adherence enhancements

Long acting formulations

Increased intensity and frequency of provider monitoring

Increased coordination and communication between medical and counseling staff

Role of concerned other in monitoring of adherence (eg: network therapy)

Supervised administration by caregiver or staff

Prescriptions left for counselor to distribute

Direct med administration up to daily

 

Integrated treatment: the role of non-medication modalities

One concept: medications synergize counseling and other tools by increasing retention, utilization, time not using

-Evidence mixed for benefit of counseling

-One study: methadone alone < + counseling < + enhanced services (job counseling, family involvement, psychiatry, medical) (McLellanet al. JAMA. 1993;269:1953-1959.)

-One study: no difference methadone with or without counseling (Schwartz et al. 2011.)

Emerging consensus: enhancement value for many but not all, need matching and stepped strategies

 

Settings and logistics

OTP (opiate treatment program) for methadone

OBOT (office based opioid treatment)

General healthcare vs specialty SUD

SAMHSA waiver for bupe

Nursing staff for XRNTX

 

Providing a full continuum of care

Inpatient detoxification and stabilization

Short term residential treatment

Long term residential treatment

Day treatment / partial hospitalization

Assisted living support for outpatient treatment (Individual Out Patient IOP “plus” Partial Hospitalization Program PHP “plus”)

Recovery housing

How the Opioid Epidemic affects Women

There is growing recognition that the United States is facing an epidemic due to an increase in opioid misuse, use disorders, and overdose, and that disparities exist between men and women with regard to both prescription opioid and heroin use. Although between 1999 and 2014 men were more likely than women to die of opioid overdoses, the gap in mortality has been closing. Between 1999 and 2010, overdose deaths from prescription pain killers increased more than 400% among women, compared to an increase of 237% among men. Although nonmedical use of prescription opioids among women has generally been decreasing since then, heroin use among women has been increasing, and increasing faster among women than among men. For example, between 2002 and 2013, heroin use among women increased 100% compared to an increase of 50% among men.

 

The picture of substance use is different for women compared to men. According to the Centers for Disease Control and Prevention (CDC), women are more likely to experience chronic pain and use prescription opioid pain medications for longer periods and in higher doses than men. Women tend to use substances differently than men, sometimes using a smaller amount of drugs for a shorter amount of time before they become dependent. For example, a national multisite effectiveness trial suggests that women who use opioids not only progress to dependence more quickly than men, but also experience more cravings than men. Psychological and emotional distress have also been identified as risk factors for hazardous prescription opioid use among women, but not among men. Many people with a substance use disorder may transition to injection drug use; thereby putting themselves at risk for viral hepatitis and HIV. Notably, new cases of hepatitis C among women increased more than 260% from 2010 to 2014, likely increasing the risk of perinatal hepatitis C transmission to their infants. Finally, women who are caregivers may face additional barriers to treatment for substance use disorders (SUDs), such as lack of childcare.
Document
2016 White Paper: Opioid Use, Misuse, and Overdose in Women

Treating Special Populations

A. Pregnancy

Unique opportunity and “motivational moment”

Methadone and buprenorphine improve:

–Maternal outcomes

–Fetal outcomes

Neonatal abstinence syndrome (NAS)

–Manageable

–Acceptable side effect

Bupeless NAS, preference for mono product (subutex)

Methadone better retention

 

B. Co-occurring psychiatric disorders

Very common in patients with SUD

Mood disorders especially common

Outcomes improved with treatment reciprocally

Most psychiatric medications compatible with relapse prevention medications with notable exception of sedative hypnotics

 

C Initiation of buprenorphine as a pain treatment strategy

At the transition from acute to chronic pain

Longer term strategy for patients with a history of opioid addiction

Possible transitional strategy for others

As part of an overall comprehensive rehabilitative approach

 

D. Focus on youth

This is a developmental disorder with adolescent onset

Addressing the problem early will maximize impact

Include and empower families to be part of the solution

Developmental barriers to treatment engagement

–Invincibility

–Immaturity

–Salience of burdens of treatment

Variable effectiveness of family leverage (or not) vs family abdication

Pushback against sense of parental dependence and restriction

Prominence of co-morbidity

 

Bottom line on use of Medications to Treat Opioid Addiction

Relapse prevention medications for opioid addiction should be the standard of care

3 good choices currently, more coming

Tailor medication and delivery and setting to individual patients

Some patients need more intensive support, structure, counseling, accountability; others not so much

Treatment works!!
What is Naloxone (Narcan)?
Naloxone is opioid antagonist (Note 1. below)
High affinity for mu receptor (Note 2. below)
Displaces bound agonist
Prevents other agonists from binding
Works within minutes
Lasts 20-90 mins
FDA approved for Intravenous (IV), subcutaneous (SC), intramuscular (IM) use
Recent FDA approved intranasal naloxone; also off-label intranasal use of naloxone for injection
Naloxone has been used for opioid reversal for 40 years in hospitals
Naloxone has been used for overdose in Emergency Departments and by paramedics for years
Since mid-1990s, provision for use outside medical setting for people at risk of overdose

NOTE 1.: An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist.

NOTE 2.: Opioids exert their pharmacological actions through three opioid receptors, mu, delta and kappa whose genes have been cloned (Oprm, Oprd1 and Oprk1, respectively). Opioid receptors in the brain are activated by a family of endogenous peptides which are released by neurons.

Opioid Overdose Prevention Programs (OOPP)

Started 1996, first program in Chicago
Started in harm prevention programs
OOPP train people at risk for overdose how to prevent overdose as well as how to recognize and respond to overdose
Participants are trained to seek help (call 911), rescue breath, administer naloxone IN or IM, and stay with the person who has overdosed

How to Train Participants in an Opioid Overdose Prevention Program before prescribing Naloxone Rescue Kits:
Have you ever had an accidental overdose?
What were the circumstances, what happened, how did you survive?
Have you ever witnessed an overdose? What did you do?
What do you do to protect yourself from overdose?
What are some risk factors for overdose?
Have you heard about naloxone/Narcan for reversal of overdose?

What is in a Rescue Kit?
Two doses of naloxone or devices
Two syringes or mucosal atomizing devices (MAD)
Instructions on use
May also include
  • Alcohol swabs
  • Face shields
  • Gloves
Videos on Use of Naloxone
LIVE! Using Injectable Naloxone to Reverse Opiate Overdose at: https://www.youtube.com/watch?v=U1frPJoWtkw&feature=player_embedded

Prescribe to Prevent: Prescribe Naloxone to Save a Life: http://prescribetoprevent.org/patient-education/videos/
Instructional Website on Naloxone: http://www.getnaloxonenow.org/index.aspx