Pharmacotherapy options for treating opioid use disorder

Pharmacotherapy options for treating opioid use disorder

Sara Maki, PharmD, Minnesota Community Care

Background: Misuse of prescription pain medications, illicit use of fentanyl or illicit drugs such as heroin contribute to the rising rate of opioid-related overdose deaths. In 2017, the Center for Disease Control and Prevention reported that approximately 130 people died every day from an overdose. This number is only rising. As discussed in a therapy update published recently in the American Journal of Health-System Pharmacists, treatment for opioid use disorder (OUD), including methadone and buprenorphine, has been shown to “reduce opioid cravings, increase treatment retention, reduce illicit opioid use, and increase overall survival.” Yet, medication-assisted treatment remains underprescribed and inaccessible to many patients. Barriers from the provider perspective may include prescribing restrictions and unfamiliarity with the current treatment options. 

Buprenorphine, methadone, and naltrexone are all considered first-line agents for the treatment of OUD by the American Society of Addiction Medicine National Practice Guideline and are FDA-approved for this indication. The choice of treatment should be a shared decision between patients and clinicians, with careful assessment of preferred treatment setting, physical dependence potential, past experiences with treatment, and evidence supporting efficacy and safety of the therapeutic options.  

Evidence: Buprenorphine is a partial opioid agonist that is available in multiple dosage forms, including sublingual tablets or strips, implant, and injection. Buprenorphine has the advantage of being more accessible than methadone, as it can be prescribed in an office-based setting by a DATA-waivered provider and filled in any community pharmacy. It also has fewer drug interactions and can be co-formulated with naloxone to prevent misuse. Fiellen et al. studied the efficacy of buprenorphine as maintenance therapy versus short-term taper in a primary-care based setting. Patients who were tapered off buprenorphine were more likely to use opioids (per self-report and urine toxicology screens). Patients in the taper group also had fewer consecutive weeks of opioid abstinence compared with those who were maintained on buprenorphine (mean abstinence in weeks, 2.70 [95% CI, 1.72-3.75] vs. 5.20 [95% CI, 4.16-6.20]). Patients who had their buprenorphine tapered were less likely to complete the 14-week trial (6 of 57 [11%] vs 37 of 56 [66%]; P <0.001).

Methadone, a full opioid agonist, can also be used to treat OUD. It may be a preferred treatment for patients who benefit from supervision of daily dosing and associated wraparound services because it is only available through certified Opioid Treatment Program facilities. However, risks include more respiratory depression and sedation than buprenorphine, along with a risk for QT prolongation. Dosing is complicated by a long half life, variable absorption, and high dose requirements to achieve full opioid receptor blockade. Mattick and colleagues demonstrated in a systematic review that methadone use was significantly more effective than placebo in preventing heroin use (RR in 6 RCTs, 0.66; 95%CI, 0.56-0.87), but did not result in lower mortality (RR in 4 RCTs, 0.48; 95% CI, 0.1-2.39). A later systematic review by the same authors concluded that methadone was superior to buprenorphine in retaining patients in treatment (RR in 5 double-blind trials, 0.83; 95% CI, 0.72-0.95). 

Naltrexone, a competitive antagonist of opioid receptors, is approved for treatment of OUD, but may not be preferred due to poor adherence outcomes. However, the oral formulation is the least expensive of all treatment options and may be appropriate for highly motivated patients who are able to take the medication daily. Initiation of the monthly depot injection can be challenging, as patients must be opioid free for 7-10 days to prevent precipitation of withdrawal. Minozzi and colleagues performed a systematic review to evaluate oral naltrexone for OUD, in which they found that naltrexone was not superior to other therapeutic options, but data was not statistically significant for the measures of retention in treatment, abstinence from illicit drug use, or adverse effects. 

Discussion and Clinical Impact: Koehl and colleagues determined that there is not sufficient evidence to make a definitive recommendation on whether buprenorphine or methadone is a more effective treatment to reduce opioid use, decrease mortality from overdose, increase daily functioning, or maintain patients in treatment. The important next step in treating OUD is expanding services to reach more patients. Choice of treatment must be a shared decision between patients and their care team, with careful consideration of previous treatment, future priorities, treatment setting, availability of medication, and potential for continuing care. 


  1. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Opioid overdose: understanding the epidemic. Published December 19, 2018. Accessed August 12, 2019. 

  2. Koehl JL, Zimmerman DE, Bridgeman PJ. Medications for management of opioid use disorder. Am J of Health-System Pharm. 2019;76(15):1097-1103. 

  3. American Society of Addiction Medicine. National practice guideline for the use of medications in the treatment of addiction involving opioid use. 2015. Published June 1, 2015. Accessed July 23, 2019. 

  4. Fiellen DA, Schottenfeld RS, Cutter CJ, Moore BA, Barry DT, O’Connor PG. Primary care-based buprenorphine taper vs maintenance therapy for prescription opioid dependence. JAMA Intern Med. 2014;174(12):1947-1954. 

  5. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev. 2009;3.

  6. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;2.

  7. Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev. 2011;2.