Medications for Opioid Use Disorder: Buprenorphine, Methadone, Naltrexone

Three FDA-approved medications treat opioid use disorder (OUD). Two of them, buprenorphine and methadone, reduce overdose mortality by approximately half compared to no treatment. The third, extended-release naltrexone, has a more specific role and is used less commonly as a first-line option for reasons explained below.¹²

These medications are not adjuncts or optional add-ons to treatment. For opioid use disorder, they are, in most clinical frameworks, the core of treatment. The rest of the plan, therapy, peer support, structured programming, is built around them.

Why medications matter so much for opioid use disorder

Opioid use disorder is different from most other substance use disorders in one specific way: untreated, it carries a substantial risk of fatal overdose, particularly in the current era, when most of the illicit opioid supply in the US contains fentanyl or fentanyl analogs.

Medications for opioid use disorder (MOUD) do two things simultaneously:

1. Reduce the acute risk of overdose death by stabilizing brain opioid receptors at a level that reduces craving, prevents withdrawal, and blocks the effects of additional illicit opioids.
2. Allow the person to engage in the rest of life, work, relationships, therapy, planning, because the daily experience of craving and withdrawal is no longer the dominant feature of each day.

Multiple large studies have shown that people receiving buprenorphine or methadone are approximately 50% less likely to die of overdose than people not receiving either.¹² This effect is not small, and it is the reason the clinical consensus across SAMHSA, CDC, the American Society of Addiction Medicine, the World Health Organization, and the National Academies of Sciences, Engineering, and Medicine is that MOUD should be available to every person with opioid use disorder who wants it.

Buprenorphine

What it is: A partial opioid agonist. Activates opioid receptors, but with a "ceiling effect", the effect plateaus at moderate doses, which makes overdose from buprenorphine itself much less likely than from full agonists like heroin, fentanyl, or methadone.

Common brand names: Suboxone (buprenorphine plus naloxone, sublingual), Subutex (buprenorphine alone, sublingual), Sublocade (monthly injection), Brixadi (weekly or monthly injection).

Who it fits: Most people with opioid use disorder. Clinical guidelines treat buprenorphine as a first-line option for the majority of patients.

How it is prescribed: Since the MAT Act of 2023 eliminated the X-waiver requirement, any clinician with a standard DEA registration can prescribe buprenorphine. It is filled at any community pharmacy and is available in primary care, outpatient substance use settings, hospital-based clinics, and via telehealth in most jurisdictions (under current DEA flexibilities).

How it is started: Traditionally, the patient waits until they are in moderate opioid withdrawal (typically 12 to 24 hours after last use, depending on the opioid) before taking the first dose, to avoid precipitated withdrawal. "Home induction" is common and well-documented. Newer protocols, including low-dose induction ("microdosing"), allow patients to start buprenorphine while still using other opioids, useful particularly in the fentanyl era.

What to expect: Once stabilized, most patients report resolution of cravings, prevention of withdrawal, and, often within days, a substantial return to baseline cognitive and emotional functioning. The medication does not produce euphoria in stabilized patients and does not interfere with work, driving, or daily life.

Risks and limitations: Diversion and misuse of buprenorphine do occur, but the risk profile is substantially safer than the street opioids the medication replaces. Liver function is typically monitored. Interactions with other sedatives (benzodiazepines, alcohol) warrant caution.

The red flag to know about: Some treatment programs require patients to taper off buprenorphine as a condition of admission. This practice is inconsistent with current ASAM 4th Edition standards and with the clinical evidence. Programs aligned with current guidelines continue MOUD across all levels of care, including residential and step-down.

Methadone

What it is: A full opioid agonist. Has been in use for opioid use disorder treatment since the 1960s and is the most thoroughly studied medication in this class.

How it is dispensed: In the US, methadone for opioid use disorder is restricted to federally certified Opioid Treatment Programs (OTPs). Patients typically begin with daily in-person dosing and, as they stabilize, earn take-home doses. A 2024 SAMHSA final rule substantially expanded take-home flexibilities, the first significant regulatory update in decades.³

Who it fits: Particularly well-suited to patients who have tried buprenorphine without adequate stabilization, patients with very high opioid tolerance (common in the fentanyl era), patients with long-standing opioid use disorder, and patients who do well in the structure of daily clinic contact.

What to expect: Once titrated to a therapeutic dose, patients typically report resolution of cravings and withdrawal and a return to functional daily life. Effective doses vary widely between individuals; the clinically appropriate dose is whatever stabilizes the patient and blocks craving. The research consistently shows that higher doses (60 to 120 mg/day and sometimes higher) produce better retention and outcomes than lower doses.

Risks and limitations: Respiratory depression is the major overdose risk, particularly during titration. Long half-life means accumulation over the first days of dosing. Interactions with other central nervous system depressants are a specific concern. Daily clinic dosing during the initial period is a logistical barrier for many.

Extended-release naltrexone (Vivitrol)

What it is: A full opioid antagonist. Blocks opioid receptors, preventing euphoria from any opioid taken while the medication is active. Does not cause physical dependence.

How it is dispensed: A monthly intramuscular injection. Administered in an office setting.

Who it fits: Patients who have completed a full opioid washout (7 to 10 days after last short-acting opioid, longer for long-acting opioids). Patients who prefer a non-agonist medication. Patients in settings where buprenorphine and methadone access is limited or contraindicated. Patients with certain occupational constraints around agonist medications.

What to expect: Once administered, the medication blocks opioid receptors for approximately four weeks. A patient who uses opioids during that period will experience significantly reduced effects. The blockade is not absolute, high doses can overcome it, sometimes with fatal consequences.

Risks and limitations: The opioid washout is a practical barrier for many patients, a period of withdrawal that is both uncomfortable and a time of substantial overdose risk if the patient returns to use. Loss of tolerance during the blockade means post-medication overdose risk is elevated if the patient uses opioids after discontinuing. Not shown to reduce overdose mortality in head-to-head comparisons with buprenorphine or methadone.¹

For these reasons, clinical guidelines generally position agonist medications (buprenorphine, methadone) as first-line for most patients, with extended-release naltrexone considered in specific circumstances.

What the medication does not do alone

Medications for opioid use disorder are central, but they do not address the full clinical picture. A good plan typically includes:

• Outpatient therapy, cognitive behavioral therapy for substance use, motivational interviewing, or similar evidence-based approaches. See CBT for SUD and motivational interviewing.
• Treatment of co-occurring conditions, depression, anxiety, PTSD, chronic pain. Untreated, these tend to drive return to use.
• Family and peer support, CRAFT for treatment-resistant loved ones, peer recovery coaching, mutual-help groups as the patient finds useful.
• Harm-reduction tools, naloxone in the home, knowledge of fentanyl contamination, never-use-alone resources if relapse occurs.
• Attention to social determinants, housing, work, financial stability, legal issues.

The medication stabilizes the biology. The rest of the plan is the rest of the plan. Medication plus a stable outpatient structure tends to outperform medication alone or therapy alone.

How to start

Practical steps for a patient or family considering MOUD:

1. Get an assessment. Any licensed clinician with substance use experience can provide one. Ask about all three medications, not just one.
2. Find a prescriber. For buprenorphine: primary care offices, outpatient substance use clinics, hospital-based programs, and most national telehealth services. For methadone: federally certified Opioid Treatment Programs (search SAMHSA's Behavioral Health Treatment Services Locator, findtreatment.gov). For extended-release naltrexone: any clinician able to administer IM injections, including primary care.
3. Verify insurance coverage. Most commercial plans, Medicaid, and Medicare cover MOUD. If cost is a barrier, sliding-scale Federally Qualified Health Centers (FQHCs) often provide it at reduced fees.
4. Start. For buprenorphine, home induction protocols are standard. For methadone, attendance at the OTP begins with daily dosing. For extended-release naltrexone, the first step is completing the opioid washout.
5. Stay. The single biggest predictor of outcome is retention. Retention is driven by medication adequacy (dose), coordination with therapy and primary care, and handling the inevitable setbacks without discharging the patient from care.

What to do if a program says no

Some treatment programs, particularly some residential programs and some older 12-step-oriented facilities, require patients to taper off MOUD as a condition of admission. This practice is inconsistent with the evidence and with current ASAM standards.

If a program requires this, keep looking. Programs that continue MOUD across all levels of care are operating at the current standard; those that do not are operating below it. See Questions to Ask a Program Before You Enroll.

The bottom line

For opioid use disorder, the medications are not optional adjuncts. They are the core of treatment, reduce overdose mortality by roughly half, and are accessible through primary care, outpatient clinics, and telehealth in most of the US. Buprenorphine is a first-line option for most patients; methadone is appropriate for a broad range of patients and particularly useful in some presentations; extended-release naltrexone has specific use cases. The plan around the medication matters, but the medication itself is the core.

What to read next

• Ways to Avoid Rehab: The Evidence-Based Guide
• The ASAM 4th Edition Criteria, Explained for Families
• Medications for Alcohol Use Disorder

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