When Naltrexone Fails for Opioid Use Disorder
Switch to opioid agonist therapy with buprenorphine or methadone, as these medications represent the evidence-based first-line treatment for opioid use disorder and should be offered when naltrexone is ineffective. 1
Understanding Naltrexone's Limited Efficacy
Naltrexone has demonstrated limited success in most populations with opioid use disorder, showing effectiveness primarily in highly motivated groups such as healthcare professionals who cannot or do not wish to take continuous opioid agonist therapy. 1, 2 The medication works by blocking mu opioid receptors, preventing the euphoric effects of opioids and providing time for patients to consider relapse consequences, but this mechanism requires exceptional patient adherence and motivation. 1, 2
Immediate Next Steps
Transition to Opioid Agonist Therapy
Offer buprenorphine or methadone maintenance therapy combined with behavioral interventions as the standard evidence-based treatment for opioid use disorder. 1
Buprenorphine can be prescribed in office-based settings by physicians who obtain a SAMHSA waiver, making it more accessible than methadone which requires certified opioid treatment programs. 1
For pregnant patients specifically, buprenorphine (without naloxone) or methadone has been associated with improved maternal outcomes and should be offered. 1
Critical Safety Consideration
Patients discontinuing naltrexone face significantly increased risk of opioid overdose and death due to decreased opioid tolerance. 1, 2 This makes the transition period particularly dangerous and requires:
- Immediate overdose education 2
- Provision of naloxone for overdose reversal 1
- Close monitoring during the transition 2
Referral and Coordination
If you cannot provide buprenorphine or methadone treatment yourself:
Arrange for the patient to receive care from a substance use disorder treatment specialist or SAMHSA-certified opioid treatment program. 1
Assist patients in finding qualified treatment providers and arrange follow-up, ensuring ongoing care coordination. 1
Never dismiss patients from your practice due to substance use disorder, as this adversely affects patient safety and represents patient abandonment. 1
Available Resources
- SAMHSA's buprenorphine physician locator (http://buprenorphine.samhsa.gov/bwns_locator) 1
- SAMHSA's Opioid Treatment Program Directory 1
- SAMHSA's Provider Clinical Support System for expert consultation 1
Why Naltrexone May Have Failed
The medication requires complete opioid abstinence before initiation and daily adherence (or monthly injections), which proves challenging for most patients. 1, 2 Unlike buprenorphine or methadone, naltrexone provides no agonist effect to reduce cravings or withdrawal symptoms, relying entirely on blocking the rewarding effects of opioids if used. 1, 2
Behavioral Therapy Integration
Regardless of medication choice, combine pharmacotherapy with behavioral interventions such as cognitive behavioral therapy, contingency management, or mutual help groups. 1 Psychosocial care significantly reduces treatment dropout rates and ongoing substance use. 2