What is medication‑assisted treatment (MAT) for substance use disorders, including its medications, dosing regimens, and required psychosocial components?

Medication-Assisted Treatment (MAT) for Substance Use Disorders

MAT is the combination of FDA-approved medications with evidence-based psychosocial interventions (such as cognitive behavioral therapy) to treat substance use disorders, primarily opioid use disorder, and this combined approach significantly reduces mortality, prevents overdoses, and improves treatment retention compared to behavioral therapy alone. 1, 2

Core Definition and Components

MAT consists of two essential elements that must be delivered together:

• Pharmacotherapy: FDA-approved medications that target the neurobiological mechanisms of addiction 3, 4
• Psychosocial interventions: Structured behavioral therapies including cognitive behavioral therapy (CBT), contingency management, motivational enhancement therapy, or other evidence-based counseling 5, 1, 6

Medication alone is insufficient—pharmacotherapy must be combined with counseling and behavioral therapies to provide comprehensive care. 1

FDA-Approved Medications for Opioid Use Disorder

Methadone (Full Opioid Agonist)

• Mechanism: Full mu-opioid receptor agonist that eliminates withdrawal symptoms and blocks euphoric effects of other opioids 1
• Efficacy: Remains the gold standard of care for opioid use disorder, with the strongest evidence for reducing opioid use and retaining patients in treatment 2
• Dosing: Administered daily under supervised conditions 1
• Critical restriction: Can only be dispensed through certified Opioid Treatment Programs (OTPs), not in general medical offices 1
• Age limitation: Restricted for patients younger than 18 years 1

Buprenorphine (Partial Opioid Agonist)

• Mechanism: Partial mu-opioid receptor agonist with high receptor affinity that reduces cravings and withdrawal while producing gentle opioid system stimulation, ameliorating the highs and lows of full agonists 5, 1
• FDA approval: Approved for patients 16 years and older since 2002 5
• Therapeutic dosing: 8-16 mg daily, with induction typically starting at 8 mg on Day 1, followed by 16 mg on Day 2 1, 6
• Administration: Sublingual tablets held under the tongue for 5-10 minutes until completely dissolved 6
• Formulations: Available as buprenorphine monotherapy (Subutex) or combined with naloxone (Suboxone) 6
• Prescribing access: Requires DEA waiver (X-waiver) but can be prescribed in general medical settings, making it more accessible than methadone 5, 7
• Pregnancy consideration: Buprenorphine monotherapy (without naloxone) is preferred over the combination product in pregnant patients 1
• Evidence: Extensive research demonstrates effectiveness in adults; growing clinical experience supports safety and efficacy in adolescents with no age-specific safety concerns identified 5, 2

Naltrexone (Opioid Antagonist)

• Mechanism: Opioid antagonist with high affinity for opioid receptors that blocks euphoric effects and reduces cravings 5, 1
• Key advantage: Very limited potential for misuse or diversion, unlike opioid agonists 5
• Formulations: Available as oral daily dosing or extended-release monthly injection, with the extended-release formulation reducing adherence burden 5
• Critical requirement: Patients must be completely opioid-free for a minimum of 7-10 days before initiation to avoid precipitated withdrawal 1
• Evidence limitations: Oral naltrexone demonstrates poor adherence and increased mortality rates; extended-release formulation shows more favorable early evidence 2
• Special populations: May be particularly useful for adolescents and young adults with co-occurring alcohol use disorder or those in unstable/unsupervised housing 5
• Adolescent evidence: Not yet rigorously studied in adolescents, but growing clinical experience and anecdotal reports support it as a promising practice 5

Required Psychosocial Components

Best practices in addiction treatment must include pharmacotherapy plus CBT or another evidence-based therapy, rather than usual clinical management or nonspecific counseling services. 5

Evidence-based behavioral interventions include:

• Cognitive Behavioral Therapy (CBT): Time-limited, multisession intervention targeting cognitive, affective, and environmental risks for substance use, providing training in behavioral self-control skills 5
• Contingency Management: Structured reinforcement approach 5, 1
• Motivational Enhancement Therapy: Patient-centered counseling to enhance motivation for change 5
• Relapse Prevention: Skills training to maintain abstinence 8

The evidence shows CBT combined with pharmacotherapy performs significantly better than usual care alone (effect size range 0.18-0.28), though CBT does not outperform other evidence-based modalities like motivational enhancement therapy or contingency management 5

Treatment Monitoring Requirements

• Regular urine drug testing: Essential for monitoring treatment progress and detecting non-prescribed substance use 1
• DSM-5 criteria assessment: Ongoing evaluation using standardized diagnostic criteria for substance use disorders 1
• Counseling frequency: Ranges from one hour per month to one hour per week depending on clinical setting and patient needs 6
• Clinical visits: Daily to weekly depending on treatment phase and medication type 6

Substances Covered by MAT

Strong Evidence for MAT:

• Opioid use disorder: Methadone, buprenorphine, naltrexone 1, 2, 3, 4
• Alcohol use disorder: Naltrexone, acamprosate, disulfiram 5
• Tobacco use disorder: FDA-approved pharmacotherapies exist 8

No Approved MAT:

• Cocaine use disorder: No FDA-approved medication-assisted therapy determined effective 8
• Stimulant use disorder: No FDA-approved medication-assisted therapy determined effective 8
• Cannabis use disorder: No FDA-approved pharmacotherapy; behavioral therapy remains the primary evidence-based approach 8

Clinical Outcomes and Prognosis

Opioid use disorder is a chronic relapsing neurologic disorder, but outcomes can be significantly improved with MAT, which reduces relapse rates, prevents overdoses, decreases mortality, and improves quality of life. 1, 2

Specific benefits demonstrated in clinical trials:

• At least doubles rates of opioid-abstinence outcomes compared to psychosocial treatment alone 2
• Reduces overdose deaths through maintained opioid tolerance and reduced illicit use 1, 2
• Decreases criminal activity associated with drug-seeking behavior 7
• Reduces infectious disease transmission (HIV, hepatitis C) by decreasing injection drug use 7
• Improves treatment retention: Patients stay engaged in care longer with MAT than behavioral therapy alone 2

Implementation in Clinical Practice

Primary Care Integration

• Primary care providers are well-positioned to provide MAT, particularly in rural settings where access to specialized addiction treatment is limited 7, 4
• Buprenorphine can be incorporated into outpatient family medicine practice using standardized protocols that allow office staff to work to the extent of their licensure 7
• Patient follow-up rates and number needed to treat are similar to other chronic medical conditions managed in primary care 7
• DEA waiver for buprenorphine prescribing can easily be obtained by family medicine and internal medicine providers 7, 3

Barriers to Address

Common obstacles limiting MAT access include:

• Confusion and stigma surrounding addiction treatment with medications 5
• Limited resources for both medication access and developmentally appropriate counseling 5
• Provider concerns about lack of mentorship and drug diversion 7
• Shortage of addiction medicine-trained providers especially in rural areas 7
• Transportation and cost-related issues for patients 7

Critical Pitfalls to Avoid

• Never prescribe medication without concurrent behavioral therapy: This violates the fundamental principle of MAT and reduces effectiveness 5, 1, 6
• Do not initiate naltrexone in patients not fully detoxified: Requires 7-10 days opioid-free to prevent precipitated withdrawal 1
• Avoid using naltrexone in patients requiring opioid pain management: It blocks pain relief from opioid agonists 8
• Monitor liver function with naltrexone: Check baseline and every 3-6 months due to hepatotoxicity risk 8
• Do not use buprenorphine/naloxone combination in pregnancy: Use buprenorphine monotherapy instead 1

Special Population Considerations

Adolescents and Young Adults

The American Academy of Pediatrics recommends that pediatricians consider offering MAT to adolescent and young adult patients with severe opioid use disorders or discuss referrals to other providers for this service. 5

• Buprenorphine is FDA-approved for ages 16 and older 5
• Access to developmentally appropriate substance use disorder counseling in community settings is essential 5
• Methadone has significant limitations for patients younger than 18 years 1

Pregnant Patients

• Buprenorphine monotherapy (Subutex) is preferred over buprenorphine/naloxone combination (Suboxone) 1
• Continued MAT during pregnancy is critical to prevent relapse and associated maternal-fetal complications 1