Considerations in Medication Assisted Treatment of

Opiate Dependence

Stephen A. Wyatt, D.O.Dept. of Psychiatry Middlesex Hospital

Middletown, CT

Disclosures

• Speaker Panels- None• Grant recipient - SAMHSA

Objectives• Review the development, science and

prescribing policies of the currently available medications for the treatment of opiate dependence.

• Understand the factors important in the decision of which treatment would be indicated.

• Understand the factors associated with the initiation of a treatment for opiate dependence.

Current Treatments

• Medically assisted withdrawal and abstinence.

• Methadone maintenance• Naltrexone: oral and injectable• Buprenorphine/naloxone

Historical Review• The 1914 Harrison Act was a commerce act

restricting the sales of narcotics, it excluded physicians treating patients

• In 1919 when the Harrison Act was ratified by the Supreme Court it excluded the treatment of opiate dependence: not considered a disease.‐ No longer was it legal for physicians to prescribe

opiates for maintaining opiate dependence or for the treatment of the disease.

‐ Medically assisted withdrawal of opiates and abstinence was the only legal treatment.

• The historical records identify the relapsing nature of this disease.

Historical Review• As the death rate from heroin injectors continued to

rise in the late 1950’s and early 1960’s, with a concurrent rise in associated crime, there was growing support for the establishment of opiate maintenance programs.

• There was an increase in federal funding for research into treating these patients.

• In 1962 Vincent Dole, MD received a grant to study the feasibility of opiate maintenance treatment. In1964 Marie Nyswander, MD, psychiatrist with experience in treating addicted patients joined the research team.

• Methadone was eventually selected as the most efficacious opiate for maintenance treatment.

Historical Review• The Comprehensive Drug Abuse Prevention

and Control Act of 1970 was a Nixon initiative in the evolution of the war on drugs.

• However, included was a Dept. of Health, Education, and Welfare authorization to improve drug abuse prevention and treatment.

• This included, under the direction of Jerome Jaffe MD, a federal effort to widen the availability of opiate maintenance programs.

Historical Review• The next approved medication for opiate

dependence was naltrexone approved in 1984. • As an opiate antagonist it blocks the opiate

receptor significantly changing the response to the administration of an opiate.‐ The lack of compliance and less reduction in craving

are thought to be the prominent problems associated with poor efficacy of the oral product.

• A sustained release form was determined to have an adequate safety profile and to be effective by the FDA in 2010.

Historical Review• With the establishment of DATA 2000 another

treatment option was made available. ‐ This act of Congress established that any schedule

III, IV, V controlled substance with FDA approval for treatment of opioid dependence could be prescribed by a “qualified” physician.

• This opened the door to buprenorphine products which are placed on schedule III.

• This resulted in availability of office based opiate dependent treatment with an agonist medication.

• This further broadened the availability of maintenance treatment.

Neurobiology: Methadone• Blocks the euphoric and sedating effects of other

opiates; • reduces the craving for other opioids• relieves symptoms associated with withdrawal

from opiates; • With stable dosing tolerance develops and does

not cause euphoria or intoxication, thus allowing a person to participate in normal daily activities including employment and family responsibilities;

• Has a long half life and is excreted slowly allowing for once a day dosing.

Methadone Treatment• Methadone maintenance treatment: a treatment

program in which addicted individuals receive daily doses of methadone.

• Multi-component treatment program‐ Encourages abstinence from other drugs of abuse

including alcohol‐ Resocialization – Sober supports‐ Vocational training‐ Coordination of healthcare

• HIV• Hepatitis C• Pregnancy

Methadone Treatment• Identified benefits

include: ‐ reduced or stopped use of

injection drugs; ‐ Reduced risk of acquiring

or transmitting diseases such as HIV, hepatitis B or C, bacterial infections, endocarditis, soft tissue infections, thrombophlebitis, tuberculosis, and STDs;

‐ possible reduction in sexual risk taking

‐ reduced risk of overdose‐ reduced mortality – the

median death rate of opiate-dependent individuals in MMT is 30 percent of the rate of those not in MMT;

‐ reduced criminal activity; ‐ improved family stability‐ Improved employment

potential; ‐ improved pregnancy

outcomes

CDC 2002

Methadone Treatment• Drawbacks

‐ Physical dependence, possibly strengthening neurobiological adaptation to opiate dependence.

‐ Daily administration at a licensed methadone treatment center is required in initial phase of treatment

‐ Early mild to moderate opiate like effects; e.g. sedation, reduction in cognitive awareness

‐ Long term maintenance effects on hormonal adaptations; reductions in testosterone, menstruation, calcium metabolism

‐ Drug/drug interactions‐ Neonatal abstinence syndrome in babies born to

methadone-maintained mothers

Neurobiology: Naltrexone

• Naltrexone, an opiate antagonist. ‐ Binds to the opiate receptor without activation

• Available as both oral and injectable formulations.‐ Oral typically daily administration, however may be given

on a three times per week schedule (Monday: 100 mg –Wednesday: 100 mg – Friday: 150 mg)

‐ Injectable form is given once monthly. • Evidence of reduction in opiate craving through a

combination of;‐ Reduced opiate receptor activation due to partial

endorphins blockade‐ Total blockade reducing initial consideration of opiate use.

• Injectable product resulting more positive results

Naltrexone TreatmentDrawbacks

• Blockade of opiate receptors interferes with opiate analgesia

• Opiate dependent patients must be detoxified from opiates before naltrexone can be started‐ If naltrexone is given to someone dependent on opioids,

opiate withdrawal with be precipitated • Compliance is the major drawback to the oral product.

‐ Patients can be maintained on observed three times a week ingestion of naltrexone with contingencies for non-compliance with positive results, e.g. criminal justice or health care worker programs.

• Injectable requires continued patient compliance after detoxification until administration.

Neurobiology: Buprenorphine

• Opioid Partial agonist‐ High affinity for mu opioid receptor ‐ Slow dissociation from receptor‐ Displaces other opioids from mu receptor

including Heroin‐ Improved safety profile due to reduction in

potential respiratory depression

Buprenorphine Treatment• Approved for office based treatment

‐ Allows for normalization of treatment in the primary care or behavioral health care settings.

‐ Allows for wider availability of agonist treatment for opioid dependence

• Opioid partial agonist properties reduce potential for overdose• Once a day administration• Fewer drug interactions described than for methadone

currently• Relative blocking of other opiates• Significant reduction in craving• Improved reentry into normal socialization• Helps to shift from drug abusing behavior to normal life

activities

Buprenorphine Treatment• Drawbacks

‐ Physical dependence, possible strengthening of the opiate dependence

‐ Potential diversion for abuse‐ Reduces the patients drive to put in place relapse

prevention behaviors due to the pharmacologic reduction in the drive to use other opiates.

‐ There is evidence of both hormonal adaptation. Neonatal abstinence syndrome can occur in babies born to mothers maintained on buprenorphine though less than that seen in the methadone treated patient.

Treatment Selection

• Logistical considerations‐ Lack of access to a methadone treatment center has been a

major limitation to this form of treatment‐ Buprenorphine has limitations in access due to a lack of

waivered physician availability though office based treatment has improved treatment access in rural areas in particular.

‐ Does a physician prescribing buprenorphine / naloxone has access to assistance with drug counseling in their community

‐ Need for detoxification from opiates prior to the administration of naltrexone. Can be a challenge due to relapse potential in the period following last dose of opioid and time necessary for opioid to be eliminated and physical dependence to resolve.

Treatment Selection • There is significant overlap in the indications of one form of therapy

over another.• Patients may have a strong bias to one form of treatment over

another. Honoring this when possible may improve compliance and effectiveness.

• Physician knowledge and level of comfort will also be a consideration.

• Patients with co-occurring medical or psychiatric illness need special consideration.‐ Poly substance abuse may need the daily oversight provided by MMT‐ Availability of buprenorphine in medical/behavioral health specialty

clinics can be an advantage in that one provider can provide medical care for multiple medical problems and opioid dependence

‐ The opportunity for the pregnant patient to be treated in an established methadone maintenance pregnancy program should be strongly considered if available. Buprenorphine has been shown to reduce both days of hospitalization for NAS and morphine dose need for treatment of NAS following delivery.

Treatment Selection

• Methadone‐ Access to a MMT treatment program‐ Better for patient in need of greater supervision‐ Those for whom the physician has:

• Greater concerns of diversion• Concerns regarding limited social supports available• Concerns about polysubstance abuse or dependence

‐ May be better for those with concurrent chronic pain and who may have periods where they need opioid analgesia.

Treatment Selection• Naltrexone

‐ For the patient currently abstinent with history of frequent relapse, opiate craving

• Recently incarcerated• Recently detoxified from opiate maintenance treatment

‐ Not anticipating surgical or other treatment, likely to need opioid analgesia.

‐ If the physician is not waivered to provide office based treatment of opioid dependence.

‐ Patient with evidence of being moderately compliant with treatment and could benefit from a monthly dosing.

‐ The injectable form can be coupled to strong contingencies that may improve compliance and outcomes.

Treatment Selection• Buprenorphine: Requires

‐ Access to waivered physician‐ Access to relapse prevention treatment to be

provided simultaneously with buprenorphine / naloxone treatment.

‐ Opportunity for coordination with other services both medical and psychiatric.

• The evidence of a reduction in drug-drug interactions with buprenorphine over methadone should be considered in those needing treatment or other medications that may alter methadone plasma concentrations (HIV HCV, Mental Illness).

‐ Moderate level of social supports available.‐ Concurrent chronic pain

Cost• Comparison of medication assisted treatment vs. no

medication for inpatient, outpatient, and pharmacy costs ‐ 29% lower for patients who received a medication for opioid

dependence versus patients treated without medication.• Injectable sustained release naltrexone had fewer opioid-

related and non–opioid-related hospitalizations than patients receiving oral medication.

• Total healthcare costs were not significantly different between oral or injectable naltrexone and buprenorphine/ naltrexone and were 49% lower than those for methadone.‐ This in part was a reflection on the increased co-morbidities in

the methadone population.

Baser, AJ of Managed Care, 2011

Medically Assisted Opioid Treatment

• Abstinence remains an option particularly in the young person or those with a low level of dependence.

• However:‐ There is strong evidence of improved outcomes

with medication assisted maintenance treatment‐ Patients should be made aware of their options‐ Treatment providers should be aware of these

medications to better educate patients and make appropriate treatment recommendations.

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