Medication-First Approach to Treating Opioid Use Disorder
Read this and more on the Opioid Crisis – in our Journal, KC Medicine.
Many studies show the effectiveness of medications over abstinence; primary care practices can provide treatment.
By Doug Burgess, MD
In the United States, drug overdoses, the majority of which are related to opiates, kill around 64,000 people every year.1 If current trends continue for the next five to six years, the number of drug overdose deaths in the 21st century will approach one million people.
Present-day drug overdose deaths exceed those numbers seen during the peak of the HIV/AIDS epidemic. However, unlike the HIV/AIDS epidemic, deaths related to drug overdose have not fallen, even though highly effective treatments exist (Fig. 1). In fact, recent data indicates that from 2016-2017, deaths related to drug overdose have increased by 22% over the previous year.
MEDICATION FIRST MODEL
While the reasons for the continued increase in overdose deaths are varied, one of the major contributing factors is a lack of access to evidence-based treatment. With close to two million people identified as having an opioid use disorder, specialty clinics lack the capacity to meet this volume on their own. Additionally, the treatment provided at specialty care clinics varies greatly from site to site. Patients are frequently required to participate in intensive psychosocial interventions as a condition of being prescribed medications.
If patients do receive medications, their treatment often consists of detoxification followed by abstinence-based treatment that is associated with relapse rates over 90%.5,6 A 2003 study by Kakko et al. compared treatment with buprenorphine to detoxification followed by intensive psychosocial interventions without buprenorphine treatment.
While the numbers in the study were small, 75% of participants treated with buprenorphine were still in treatment at one year, but no participant remained in the psychosocial-intervention-only group. Within two weeks, 75% of participants in this group had dropped out of treatment and, even more alarmingly, 20% of them were dead by the conclusion of the study.
Treating opioid use disorders within primary care settings offers many advantages. In addition to increased capacity and ease of access, patients may feel less stigmatized if their care is delivered in a traditional medical setting. Additionally, opioid use disorders are often first diagnosed in primary care clinics so access to readily available treatment can reduce barriers and cut down on delays in starting treatment.
There is ample evidence supporting the effectiveness of treating opioid use disorders within a traditional medical setting. In 1997, France responded to a marked rise in opioid overdoses by approving buprenorphine treatment without requiring specialized training or certification. Among primary care providers, 20% began to offer this treatment in their standard practice locations. This increase in buprenorphine prescriptions was correlated to a decrease in opioid-related mortality. Similar results have been demonstrated in the United States. In Baltimore, increased treatment with buprenorphine, and to a lesser extent methadone, resulted in over a 50% reduction in overdose deaths.
Some clinicians may be reluctant to treat opioid use disorders in a primary care setting due to a lack of immediate access to psychosocial interventions such as group therapy and individual counseling. However, a recent Cochrane review found that there was no impact on retention in treatment or illicit opioid use when intensive psychosocial interventions were added to methadone or buprenorphine alone.6 Another study found a 75% reduction in illicit opioid use as measured by urine toxicology screens when wait-listed patients were provided with bridge buprenorphine. They received minimal interventions outside of treatment with buprenorphine.
Psychosocial interventions will continue to play an important role in the treatment of opioid use disorders and should be offered to patients. However, the research demonstrates that the most effective treatment for opioid use disorders is medication. This evidence supports a new approach to the treatment of opioid use disorders where there is rapid access to medications with minimal barriers to starting and continuing treatment. This model has been referred to as the “Medication First” model because it emphasizes the use of medication as an essential first step in engaging patients in treatment. Providing medication up front allows patients to participate in other interventions without suffering through opioid withdrawal. It also decreases the likelihood that they will die while awaiting intake at a specialty clinic.
INITIATING TREATMENT OF OPIOID — USE DISORDER
Screening instruments such as the Drug Abuse Screening Test (DAST)can be useful in identifying individuals who warrant further assessment. Further evaluation needs to establish a diagnosis of Opioid Use Disorder according to the DSM-512 or Opioid Dependence Syndrome according to The International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10).
It is important to distinguish between patients who may be exhibiting symptoms of physical dependence and those with an opioid use disorder. Patients with physical dependence may be successful with a gradual taper of opioids and alternative pain management strategies. The American Society of Addiction Medicine (ASAM) National Practice Guidelines provides a comprehensive overview of considerations when evaluating patients for opioid use disorder. Special consideration should be given in screening for infectious diseases (hepatitis, HIV and tuberculosis), acute trauma, pregnancy and cellulitis or abscesses.
Laboratory testing should include a complete blood count, liver function tests, urine toxicology and tests for hepatitis C and HIV. Testing for other sexually transmitted infections and pregnancy is considered on a case-by-case basis. Patients should undergo screening for other substance use and any co-occurring mental health conditions.
A thorough review of active medications should be completed. Concomitant prescription of benzodiazepines should be used with extreme caution in patients with an opioid use disorder. The FDA recently reviewed risk data on the combined use of benzodiazepines and methadone or buprenorphine. In August of 2017, they issued a drug safety warning that identified an increased risk of serious side effects but concluded that “the opioid addiction medications buprenorphine and methadone should not be withheld from patients taking benzodiazepines or other drugs that depress the central nervous system (CNS).”
MEDICATIONS — USED IN THE TREATMENT OF OPIOID — USE DISORDERS
There are three classes of medication with FDA approval for the treatment of opioid use disorders: full opioid agonists, partial opioid agonists and full opioid antagonists. All three have proven efficacy but vary significantly in their mechanism of action and initiation procedures. The choice of which agent to use is based on a number of factors including access to treatment, previous patient experience and clinician assessment. The goal of treatment is to reduce mortality, decrease use of illicit substances, prevent withdrawal and cravings, and reduce the symptoms associated with illicit opioid use. Treatment should be continued for as long as the patient is benefiting, remains at risk for relapse, has no serious side effects and wants to remain in treatment.
All patients with an opioid use disorder should be counseled on the use of naloxone. This is covered by most insurance companies and is available in Missouri without a prescription. The CDC recommends naloxone be made available to all patients prescribed more than 50 morphine milligram equivalents per day.
While methadone can be prescribed in the management of pain, methadone for the treatment of opioid use disorder can only be provided by opioid treatment programs (OTPs). A recent search of the U.S. Substance Abuse and Mental Health Administration’s opioid treatment program directory identified 16 OTPs in the state of Missouri, all of which were located in metropolitan areas. In cases where hospitalization is required and a patient would be unable to present to their OTP, their methadone can be provided after verification of dosage with the treating OTP.
Methadone is a full agonist at the mu opioid receptor and has a long half-life which limits the euphoria as well as peaks and valleys which can contribute to misuse. When starting treatment at an OTP, individuals are required to present on a daily basis to have methadone dispensed. The dosage is titrated until withdrawal symptoms and cravings resolve. After they are stabilized, patients are able to earn take-home doses based on their progress in the program. After one year, they are eligible for up to two weeks of take-home treatment and after two years, they can take home up to four weeks.
Important considerations in treating individuals who are receiving methadone include the potential for QT prolongation and interactions with other medications which can significantly increase or decrease methadone metabolism. Periodic EKGs may be useful in monitoring patients with conditions that predispose them to cardiac arrhythmias. A review for potentially harmful medication interactions should be completed prior to starting or stopping any medications.
The Drug Abuse Treatment Act of 2000 (DATA) allows practitioners to prescribe buprenorphine in any clinic location including offices, community hospitals, health departments and correctional facilities. Providers must first receive a waiver from the Drug Enforcement Administration which requires them to complete eight hours of training, offer referral for psychosocial interventions and keep a log of the patients they are treating at any given time. They are limited to 30 patients in the first year, 100 patients in their second year and 275 patients after that.
Buprenorphine is available in several formulations which are dissolved under the tongue. Many of these options contain naloxone which has poor oral bio-availability but acts as an abuse deterrent. A new extended-release formulation was also approved by the Food and Drug Administration in December 2017. This is a long-active injectable which is administered every four weeks.
Buprenorphine acts as a partial agonist at the mu opioid receptor site and an antagonist at the kappa opioid receptor site. Given that it acts as a partial agonist, there is a lower risk of overdose and respiratory suppression. Most individuals experience a ceiling effect at 24-32 mg; higher dosages do not produce a greater effect. Buprenorphine binds with high affinity to mu-opioid sites so consideration must be given to the management of acute pain. Buprenorphine’s high affinity for mu opioid receptors also means that prescription opioids may have significantly reduced efficacy in treating acute pain. Non-opioid pain medications and nerve blocks will continue to be effective alternatives.
Care must also be taken when starting people on buprenorphine. Individuals must be in mild to moderate opioid withdrawal before the buprenorphine is initiated or they could experience precipitated withdrawal due to buprenorphine displacing other opioids in the body. In order to avoid this, the medication should be started at 2-4 mg and titrated gradually, with additional dosages taken every 1-2 hours until symptoms of withdrawal and opioid cravings resolve. For a more detailed explanation of the induction process, refer to the ASAM’s National Practice Guideline.
The induction process can be completed in-office, but recent trends have moved towards providing appropriate patients with a small supply of buprenorphine along with instructions on how to complete the induction at home. This can help to decrease the burden placed on primary care clinics, and many patients feel more comfortable completing the process at home. There have been over 1,100 cases of home induction reported in the medical literature16 and there are several studies which support the safety of this approach. The consensus opinion of ASAM’s National Practice Guideline Committee supports the use of home induction.
Naltrexone works as a full antagonist at the mu opioid receptor site. It requires that patients be abstinent from opioids for 7-10 days which can make it difficult to initiate in individuals who are likely to experience significant withdrawal symptoms. However, unlike treatment with methadone or buprenorphine, naltrexone does not produce withdrawal symptoms if it is suddenly discontinued. Adherence with oral formulations tends to be poor, but it is also available in a long-acting formulation that is administered every four weeks. This has been shown to be effective in helping people maintain abstinence and possibly reduce cravings for opioids. There have been some rare cases of liver toxicity associated with naltrexone, so liver function tests should be performed periodically and in cases where there are signs and symptoms of toxicity. In situations where acute pain management is required, opioids will be ineffective, but non-opioid pain medications and nerve blocks will continue to be effective alternatives.
THE BIG PICTURE
The opioid epidemic is the most severe substance-use-related epidemic in the history of the United States. Traditional approaches to treatment have been ineffective, and deaths continue to accumulate. Communities that have expanded access to effective treatments by extending services to standard medical settings have demonstrated a remarkable reduction in mortality rates. It is imperative that our medical community reduce unnecessary barriers and obstacles to accessing lifesaving medication. While the medications may be new or unfamiliar to some, with time and practice, they can become as easy to use as many of the medications currently prescribed during routine office visits.
Doug Burgess, MD, is medical director for outpatient psychiatry at Truman Medical Centers and assistant professor of psychiatry at the University of Missouri-Kansas City. He can be reached at (816) 374-1875, firstname.lastname@example.org.
- Wide-ranging online data for epidemiologic research (WONDER. Atlanta, GA: CDC, National Center for Health Statistics; 2000-2016. Available at http://wonder.cdc.gov.
- Centers for Disease Control and Prevention (CDC), National Center for Health Statistics (2017). Drug overdose deaths in the United States, 1999-2016. NCHS Data Brief
- NCHS, National Vital Statistics Estimates for 2017 are based on provisional data. Estimates for 2015 and 2016 are based on final data (available from: https://www.cdc.gov/nchs/ nvss/mortality_public_use_data.htm).
- Prescription Opioid Use, Misuse and Use Disorder in S. Adults. Annals of Internal Medicine. 2017; 167(5).
- Volkow ND, Frieden TR, Hyde PS, Cha Medication-assisted therapies- tackling the opioid-overdose epidemic. New England Journal of Medicine, 2014; 370 (22), 2063-66.
- Mattick RP, Kimber J, Breen C, Davali M. Bupreorphine maintenance placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2(2). 2008.
- Kakko J, et 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomized, placebo-controlled trial. Lancet. 2003; 361, 662–668.
- Carrieri MP, et Buprenorphine use: the international experience. Clinical Infectious Diseases 2006; 43: Supplement 4, S197-S215.
- Schwartz RP, et al. Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, 1995–2009. American Journal of Public 2013; 103(5): 917-922.
- Sigmon SC., et al. Bridging waitlist delays with interim buprenorphine treatment: Initial feasibility. Addictive 2015; 51: 136-142.
- Yudko E, Lozhkina O, Fouts A comprehensive review of the psychometric properties of the Drug Abuse Screening Test. J Subst Abuse Treat. 2007; 32: 189-198.
- American Psychiatric Diagnostic and Statistical Manual of Mental Disorders, 5th edition Washington, D.C.: American Psychiatric Association; 2013.
- World Health The ICD-10 classification of mental and behavioral disorders: clinical descriptions and diagnostic guidelines. 1992. http://www.who.int/ (last accessed 13 September 2017).
- Kampman K, Jarvis American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. Journal of Addiction Medicine. 2015; 9(5): 358-367. doi:10.1097/ ADM.0000000000000166.
- FDA Drug Safety Sept. 20, 2017. https:// www.fda.gov/Drugs/DrugSafety/ucm575307.htm
- Gunderson Models of Buprenorphine Induction. PCSS MAT Training. Online Module
- Cunningham CO, Giovanniello A, Li X, et A comparison of buprenorphine induction strategies: patient-centered home-based inductions versus standard-of-care office-based inductions. J Subst Abuse Treat. 2011; 40: 349–356.
- Lee JD, Grossman E, DiRocco D, et Home buprenorphine/ naloxone induction in primary care. J Gen Intern Med. 2009; 24: 226–232. Lee JD, Vocci F, Fiellin DA. Unobserved “Home” Induction Onto Buprenorphine. J Addict Med. 2014; 8: 299-308.
- Gibson AE, Doran CM, Bell JR, et A comparison of buprenorphine treatment in clinic and primary care settings: a randomized trial. Med J Aust. 2003.179:38–42.
- Krupitsky E, Nunes EV, Ling W, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind,placebo-controlled, multicentre randomized trial. Lancet. 2011; 377: 1506-1513.
- Syed YY, Keating GM. Extended-release intramuscular naltrexone (VIVITROL®): a review of its use in the prevention of relapse to opioid dependence in detoxified CNS Drugs. 2013; 27: 851-861.