What are the recommended treatments for opioid dependency?

Treatment of Opioid Dependency

Clinicians should offer or arrange medication-assisted treatment (MAT) with buprenorphine or methadone combined with behavioral therapies as first-line treatment for opioid use disorder. 1

First-Line Medication-Assisted Treatment

Buprenorphine (Preferred for Most Settings)

• Buprenorphine or buprenorphine-naloxone combination is highly effective for preventing relapse and maintaining abstinence in patients with opioid use disorder, including those with prescription opioid dependence. 1
• The standard approach involves stabilization on sublingual/buccal buprenorphine (8-24 mg daily) for at least 7 consecutive days before considering transition to long-acting formulations. 2
• Long-acting injectable buprenorphine (Sublocade) can be initiated after stabilization, with first two monthly doses at 300 mg followed by maintenance doses of 100 mg monthly. 2
• Buprenorphine has a ceiling effect for respiratory depression, making it safer than full agonists with lower risk of fatal overdose. 3
• This medication can be prescribed in office-based settings by physicians who complete 8 hours of training and obtain a DEA waiver. 1

Methadone (Gold Standard for Severe Cases)

• Methadone maintenance therapy remains the gold standard with the strongest evidence for reducing opioid use and retaining patients in treatment. 4
• Methadone can only be dispensed through federally certified Opioid Treatment Programs (OTPs) registered by SAMHSA and DEA. 5
• This restriction limits accessibility but provides structured, supervised treatment for patients with severe opioid use disorder. 1

Behavioral Therapies (Essential Component)

• All medication-assisted treatment must be combined with behavioral therapies to optimize outcomes. 1, 2
• Cognitive behavioral therapy (CBT) has been shown to reduce opioid misuse, increase retention during maintenance therapy, and improve compliance after detoxification. 1
• Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use without medication support. 6

Alternative Medication: Naltrexone

When to Consider Naltrexone

• Naltrexone is most appropriate for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy. 7
• Extended-release injectable naltrexone (Vivitrol, 380 mg monthly) shows more promise than oral formulations due to improved adherence. 7
• Naltrexone has advantages of no misuse potential, no diversion risk, and no overdose risk from the medication itself. 4

Critical Safety Requirements for Naltrexone

• Patients must be completely opioid-free for 7-10 days (short-acting opioids) or up to 2 weeks (buprenorphine/methadone) before starting naltrexone to avoid precipitated withdrawal. 8
• Precipitated withdrawal can be severe enough to require ICU admission, with symptoms including confusion, hallucinations, significant fluid losses, and cardiovascular instability. 8
• Perform naloxone challenge test if any question of occult opioid dependence exists, though this is not completely reliable. 8
• Monitor liver function tests at baseline and every 3-6 months due to hepatotoxicity risk. 7

Naltrexone Limitations

• Oral naltrexone demonstrates poor adherence and increased mortality rates compared to agonist therapies. 4
• Patients who discontinue naltrexone have markedly increased risk of fatal overdose due to decreased opioid tolerance. 8
• Cannot be used in patients requiring opioids for pain control as it blocks analgesic effects. 7

Treatment Algorithm

Step 1: Assessment and Diagnosis

• Assess for opioid use disorder using DSM-5 criteria (≥2 criteria within 12 months indicating problematic pattern causing impairment or distress). 1
• Evaluate for concurrent benzodiazepine use, which significantly increases risk of fatal respiratory depression. 1
• Screen for comorbid psychiatric conditions and other substance use disorders. 1

Step 2: Medication Selection Priority

1. First choice: Buprenorphine/buprenorphine-naloxone for most patients due to office-based availability, favorable safety profile, and proven efficacy. 1, 9
2. Second choice: Methadone for patients with severe opioid use disorder, prior buprenorphine failure, or need for highly structured treatment. 4, 6
3. Third choice: Extended-release naltrexone only for highly motivated patients who refuse agonist therapy and can safely complete opioid-free period. 7, 4

Step 3: Initiation Protocol

• For buprenorphine: Begin when patient shows mild-moderate withdrawal symptoms to avoid precipitated withdrawal. 2
• For methadone: Initiate in certified OTP with appropriate dosing titration. 5
• For naltrexone: Ensure 7-10 day opioid-free period minimum, consider naloxone challenge, monitor closely for precipitated withdrawal. 8

Step 4: Concurrent Behavioral Treatment

• Arrange evidence-based psychotherapy (CBT preferred) alongside medication treatment. 1
• Address comorbid mental health conditions with appropriate non-benzodiazepine treatments. 1
• Coordinate care with mental health professionals and addiction specialists. 1

Special Populations

Adolescents and Young Adults

• The American Academy of Pediatrics recommends offering medication-assisted treatment to adolescents with severe opioid use disorder. 1
• Buprenorphine is FDA-approved for patients 16 years and older. 1
• Extended-release naltrexone may be considered for adolescents, particularly those with co-occurring alcohol use disorder. 1

Pregnant Women

• Buprenorphine monotherapy (not combination with naloxone) has been associated with improved maternal outcomes in pregnant women with opioid use disorder. 2
• Medication-assisted therapy during pregnancy is strongly preferred over continued opioid use or withdrawal. 2

Common Pitfalls to Avoid

• Never taper opioids and benzodiazepines simultaneously - taper opioids first due to greater risks of benzodiazepine withdrawal. 1
• Do not start naltrexone without ensuring adequate opioid-free period, as precipitated withdrawal can be life-threatening. 8
• Avoid medication-assisted detoxification alone without maintenance therapy, as outcomes are similarly poor to behavioral interventions alone. 6
• Do not fail to provide naloxone for overdose prevention to all patients with opioid use disorder. 2
• Never abruptly discontinue maintenance therapy without close monitoring and support, as this dramatically increases overdose risk. 8

Addressing Treatment Barriers

• Insurance coverage limitations for buprenorphine and limited OTP capacity often create access barriers. 1
• Primary care providers should obtain buprenorphine prescribing waivers to increase treatment availability, especially in rural areas. 2, 10
• Identify local treatment resources and work to ensure sufficient community treatment capacity. 1
• Combat stigmatization that makes treatment less accessible through provider education and patient advocacy. 10