āļ§ัāļ™āđ€āļŠāļēāļĢ์āļ—ี่ 6 āļ˜ัāļ™āļ§āļēāļ„āļĄ āļž.āļĻ. 2568

Opioid Use Disorder (OUD)

ðŸĐš Opioid Use Disorder (OUD)

🔎 Introduction

  • OUD = chronic relapsing illness āļˆāļēāļ misuse āļ‚āļ­āļ‡ opioids (prescribed, diverted āļŦāļĢืāļ­ illicit āđ€āļŠ่āļ™ heroin, fentanyl)
  • āļŠ่āļ‡āļœāļĨ morbidity āđāļĨāļ° mortality āļŠูāļ‡āļĄāļēāļ (overdose, infection, trauma)
  • Treatment goals = reduce relapse options: methadone, buprenorphine, naltrexone āđāļĨāļ° psychosocial interventions

📊 Epidemiology

  • Epidemic āļ•ั้āļ‡āđāļ•่ 1990s āļ—ั้āļ‡ illicit āđāļĨāļ° prescribed opioids
  • Synthetic opioid overdose (fentanyl) āđ€āļžิ่āļĄāļ‚ึ้āļ™āļ•่āļ­āđ€āļ™ื่āļ­āļ‡
  • āļœู้āļ›่āļ§āļĒ OUD āļˆāļģāļ™āļ§āļ™āļĄāļēāļāđ€āļĢิ่āļĄāļˆāļēāļ misuse prescription opioids
  • Pregnant OUD āđ€āļžิ่āļĄāļ‚ึ้āļ™ neonatal abstinence syndrome āđ€āļžิ่āļĄ

Risk factors

  • Personal/substance use history
  • Younger age
  • Chronic pain with opioid therapy
  • Mental disorders
  • Childhood abuse/neglect

ðŸĐđ Practical Recommendations for Safe Prescribing

ðŸŽŊ āđƒāļŠ้ multimodal analgesia first
Opioids āđ€āļ›็āļ™ adjunct āđ€āļ—่āļēāļ™ั้āļ™

Clinical Strategy

Rationale

āđƒāļŠ้ lowest effective dose

āļĨāļ” tolerance/misuse

āļĢāļ°āļĒāļ°āļŠั้āļ™āļ—ี่āļŠุāļ” (3 āļ§ัāļ™ āđ€āļŦāļĄāļēāļ°āļŠāļĄāļ—ี่āļŠุāļ”, 7 āļ§ัāļ™ max)**

āļĨāļ” transition long-term

Avoid long-acting opioids & avoid tramadol* for acute pain

Risk long-term / overdose

Reassess pain function goals

āļĨāļ” unnecessary continuation

Prescribe naloxone if risk factors present

āļĨāļ” fatal overdose

*Tramadol: āđāļĄ้āļ–ูāļāļĄāļ­āļ‡āļ§่āļē mild āđāļ•่āļ‚้āļ­āļĄูāļĨāļŦāļĨāļēāļĒāļŠุāļ”āļŠี้āļ§่āļē Risk persistent use āļŠูāļ‡āļāļ§่āļē immediate-release opioids āļ­ื่āļ™āđ†


⚙️ Pharmacology

Mechanism

  • Opioids bind mu receptors analgesia, euphoria, respiratory depression
  • Chronic exposure neuroadaptation tolerance, physical dependence, withdrawal
  • Rapid BBB penetration in heroin quick “high”

Genetic concern

  • CYP2D6 ultrarapid metabolizer codeine morphine toxicity risk

🧑‍⚕️ Clinical Manifestations

Presentations:

1.       Acute intoxication miosis, sedation (“nodding”), respiratory depression

2.       Withdrawal lacrimation, rhinorrhea, yawning, GI symptoms, piloerection

3.       No acute symptoms but impaired social/health function

Severe OUD life centered around drug seeking, legal & social problems


🚑 Health Consequences

Major complications:

  • Infections: cellulitis, abscess, endocarditis, osteomyelitis, HIV, Hep B/C
  • GI effects: opioid-induced constipation, narcotic bowel syndrome
  • Pain: opioid-induced hyperalgesia
  • Neuro: heroin-associated leukoencephalopathy, opioid amnestic syndrome
  • Liver fibrosis
  • Overdose death āļ­āļĒ่āļēāļ‡āļŠัāļ”āđ€āļˆāļ™
  • Trauma: MVAs, falls fracture risk (esp. early in treatment)
  • Cancer risk (related exposures: hepatitis, smoking)

📈 Disease Course

  • ~50% of heroin users develop OUD
  • āļœู้āđƒāļŠ้ opioid analgesics 10–20% āļžัāļ’āļ™āļēāđ€āļ›็āļ™ OUD
  • High relapse rate āļŦāļēāļāđ„āļĄ่āļĄี maintenance therapy

🧊 Screening & Assessment

āđāļ™āļ°āļ™āļģāļ„ัāļ”āļāļĢāļ­āļ‡ āđƒāļ™āļœู้āļ›่āļ§āļĒāļ—ี่āļĄี risk āļŦāļĢืāļ­ evidence āļ‚āļ­āļ‡ opioid misuse
āļ•ัāļ§ screening tools:

  • RODS (8 items)
  • OWLS (4 items, āļŠāļģāļŦāļĢัāļš long-term opioid Rx)

History

  • Substances used, route (IV risk āļŠูāļ‡āļŠุāļ”), tolerance, last use
  • Spending behavior āļ„āļ§āļēāļĄāļĢุāļ™āđāļĢāļ‡āļ‚āļ­āļ‡ dependence
  • Treatment history, legal/social consequences

Physical Exam

  • Track marks, septal perforation, murmurs (IE), hepatomegaly, lymphadenopathy

Labs

  • Urine drug screen: morphine/heroin detectable 1–3 days
    • Heroin-specific 6-MAM
    • Fentanyl, methadone, buprenorphine āļ•้āļ­āļ‡āļ•āļĢāļ§āļˆāđ€āļ‰āļžāļēāļ°
  • Infection screening: HIV, Hep A/B/C, syphilis, TB
  • CBC, LFTs

Prescription Monitoring Program āļ›้āļ­āļ‡āļัāļ™ doctor shopping


🧠 Diagnosis (DSM-5-TR)

OUD = 2/11 criteria āļ āļēāļĒāđƒāļ™ 12 āđ€āļ”ืāļ­āļ™
āđāļš่āļ‡āđ€āļ›็āļ™ mild (2–3), moderate (4–5), severe (6)
(āđƒāļŠ้ table DSM-5-TR OUD criteria āđƒāļ™āļāļēāļĢāļ§ิāļ™ิāļˆāļ‰ัāļĒ)

āļŦāļĨัāļāļāļēāļĢāļˆāļģāļ‡่āļēāļĒ 4 āļāļĨุ่āļĄāļ­āļēāļāļēāļĢ:

1.       Loss of control

2.       Social impairment

3.       Risky use

4.       Pharmacologic: tolerance & withdrawal


ðŸ’Ą Key Clinical Takeaways

āļ›āļĢāļ°āđ€āļ”็āļ™

āļ‚้āļ­āļ„āļ§āļĢāļĢู้

āļœู้āļ›่āļ§āļĒ OUD āļ•āļēāļĒāđƒāļ™āļ­ัāļ•āļĢāļēāļŠูāļ‡

overdose, trauma

Rapid tolerance āđƒāļŠ้āđ€āļžื่āļ­āļัāļ™ withdrawal

āļĄāļēāļāļāļ§่āļēāļ•้āļ­āļ‡āļāļēāļĢ euphoria

Fentanyl āļāļģāļĨัāļ‡āđ€āļ›็āļ™āļ•ัāļ§āļ‚ัāļš overdose epidemic

āļ•āļĢāļ§āļˆ urine āļ•้āļ­āļ‡āļŠั่āļ‡āđ€āļ‰āļžāļēāļ°

Maintenance treatment (methadone/buprenorphine)

āļĨāļ” mortality āđāļĨāļ° relapse āļ­āļĒ่āļēāļ‡āļĄีāļ™ัāļĒāļŠāļģāļ„ัāļ

Infection screening & vaccination

āļŠāļģāļ„ัāļāļĄāļēāļāđƒāļ™ IVDU


Treatment for Opioid Use Disorder (OUD)

1. āļŦāļĨัāļāļ„ิāļ”āļ—ั่āļ§āđ„āļ›

  • āļœู้āļ›่āļ§āļĒāļŠ่āļ§āļ™āđƒāļŦāļ่ (āļĢāļ§āļĄāļ–ึāļ‡āļ„āļ™āļ—ี่āļœ่āļēāļ™ medically supervised withdrawal āđāļĨ้āļ§) āļĄัāļāļ•้āļ­āļ‡āļāļēāļĢ long-term treatment āđ€āļžื่āļ­āļĨāļ”āļāļēāļĢāļāļĨัāļšāđ„āļ›āđƒāļŠ้āļ‹้āļģ (relapse)
  • First-line = āđƒāļŠ้āļĒāļē (Medication for OUD, MOUD) + adjunct psychosocial treatment
    • āļĒāļēāļ—ี่āđƒāļŠ้: methadone, buprenorphine, naltrexone (oral / LAI)
    • āļšāļēāļ‡āļĢāļēāļĒāļ­āļēāļˆāđƒāļŠ้āđāļ•่āļĒāļē āļŦāļĢืāļ­āđāļ•่ psychosocial āļ•āļēāļĄāļ‚้āļ­āļˆāļģāļัāļ”āđāļĨāļ°āļ„āļ§āļēāļĄāļ•้āļ­āļ‡āļāļēāļĢāļœู้āļ›่āļ§āļĒ

2. āļ่āļ­āļ™āđ€āļĢิ่āļĄāļāļēāļĢāļĢัāļāļĐāļē

2.1 Shared decision-making

  • āļ­āļ˜ิāļšāļēāļĒāļ•ัāļ§āđ€āļĨืāļ­āļ: methadone, buprenorphine, naltrexone, psychosocial āļĨ้āļ§āļ™ āđ†
  • āđ€āļ™้āļ™āļ§่āļē pharmacotherapy āļĨāļ” mortality āđāļĨāļ° relapse āļ­āļĒ่āļēāļ‡āļŠัāļ”āđ€āļˆāļ™ āđāļ•่āđ€āļ›ิāļ”āđ‚āļ­āļāļēāļŠāđƒāļŦ้āļ„āļ™āđ„āļ‚้āđ€āļĨืāļ­āļāđāļ™āļ§āļ—āļēāļ‡
  • āļ„āļ™āđ„āļ‚้āļ—ี่ treatment āļ•āļĢāļ‡āļัāļš “preference” āļĄี outcome āļ”ีāļāļ§่āļē

2.2 āļ›āļĢāļ°āđ€āļĄิāļ™āļ„āļ§āļēāļĄāļĢุāļ™āđāļĢāļ‡ OUD

  • āđƒāļŠ้ DSM-5-TR OUD criteria āđāļš่āļ‡ mild / moderate / severe
  • āđƒāļ™āļ—āļēāļ‡āļ›āļิāļšัāļ•ิ āđ€āļ™้āļ™:
    • āļĄี physical dependence āļŦāļĢืāļ­āđ„āļĄ่
    • āļ–้āļēāļĄี tolerance āļŠัāļ” + withdrawal āļŠัāļ” āļ–ืāļ­āđ€āļ›็āļ™ moderate–severe OUD
  • DSM-5-TR opioid withdrawal = 3 āđƒāļ™āļāļĨุ่āļĄāļ­āļēāļāļēāļĢ:
    • dysphoric mood, N/V, muscle aches, lacrimation/rhinorrhea, pupillary dilation/piloerection/sweating, diarrhea, yawning, fever, insomnia
  • āļ›āļĢāļ°āđ€āļĄิāļ™āđ€āļŠāļĄāļ­āļ§่āļē āļĢāļ°āļ”ัāļš physical dependence āļŠูāļ‡āđāļ„่āđ„āļŦāļ™ (āđ€āļŠ่āļ™ āđƒāļŠ้ fentanyl āļ‚āļ™āļēāļ”āļŠูāļ‡)

2.3 Education & overdose prevention

  • āđƒāļŦ้ education āđ€āļĢื่āļ­āļ‡ overdose + āđāļˆāļ naloxone āđƒāļŦ้āļœู้āļ›่āļ§āļĒ/āļ„āļĢāļ­āļšāļ„āļĢัāļ§
  • āļĒิ่āļ‡āļŠāļģāļ„ัāļāđƒāļ™āļœู้āļ—ี่ āđ„āļĄ่āđƒāļŠ้ MOUD āđ€āļŠี่āļĒāļ‡ overdose āļŠูāļ‡āļāļ§่āļē

3. Initial Treatment Strategy

3.1 āļāļĨุ่āļĄāļĄี physical dependence (moderate–severe OUD)

āđāļ™āļ§āļ—āļēāļ‡āļ—ี่āđāļ™āļ°āļ™āļģ

  • āđƒāļŦ้ pharmacotherapy + psychosocial intervention
    • āļ”ีāļāļ§่āļē MOUD alone āļŦāļĢืāļ­ psychosocial alone

āđ€āļŦāļ•ุāļœāļĨāđƒāļŦ้ MOUD āđ€āļ›็āļ™ first-line

  • āļĨāļ” relapse
  • āđ€āļžิ่āļĄ retention
  • āļĨāļ” all-cause mortality & suicide

3.2 āđ€āļĨืāļ­āļāļĒāļē – agonist vs antagonist

āļ—āļģāđ„āļĄāļˆึāļ‡ prefer agonist (methadone / buprenorphine) > naltrexone

1.       āļĨāļ” mortality āđ„āļ”้āļŠัāļ”āđ€āļˆāļ™

o   meta-analysis: āļŠ่āļ§āļ‡āļ—ี่āđ„āļ”้āļĢัāļš opioid agonist mortality āļĨāļ”āļĨāļ‡āđ€āļืāļ­āļšāļ„āļĢึ่āļ‡āđ€āļ—ีāļĒāļšāļัāļšāđ„āļĄ่āđ„āļ”้āļĢัāļāļĐāļē

2.       āđ„āļĄ่āļ•้āļ­āļ‡āļĢāļ­āļ–āļ­āļ™āļĒāļēāđ€āļ•็āļĄāļ—ี่āļ่āļ­āļ™āđ€āļĢิ่āļĄ

o   āđ€āļĢิ่āļĄ methadone/buprenorphine āđ„āļ”้āđāļĄ้āļĒัāļ‡āđƒāļŠ้ opioid āļ­āļĒู่

o   āđāļ•่ naltrexone āļ•้āļ­āļ‡āļœ่āļēāļ™ withdrawal āđ€āļ•็āļĄ āđ† 7–10 āļ§ัāļ™ āļĒāļēāļāđƒāļ™ real world, induction fail āļŠูāļ‡

3.       Outcome

o   āļœู้āļ—ี่ “induce LAI naltrexone āđ„āļĄ่āļŠāļģāđ€āļĢ็ā relapse āđ€āļĢ็āļ§

o   āļ–้āļēāļœ่āļēāļ™ induction āđ„āļ”้āđāļĨ้āļ§ LAI naltrexone efficacy āđƒāļāļĨ้āđ€āļ„ีāļĒāļ‡ buprenorphine


4. āļāļēāļĢāđ€āļĨืāļ­āļāļĢāļ°āļŦāļ§่āļēāļ‡ Buprenorphine vs Methadone

āļŦāļĨัāļāđƒāļŠ้āđ€āļĨืāļ­āļ

  • āļĢāļ°āļ”ัāļš dependence (āđ‚āļ”āļĒāđ€āļ‰āļžāļēāļ° fentanyl/high-potency use)
  • āļ›āļĢāļ°āļ§ัāļ•ิ response āļ•่āļ­āļāļēāļĢāļĢัāļāļĐāļēāđ€āļ”ิāļĄ
  • āđ‚āļ­āļāļēāļŠāļāļēāļĢ misuse/diversion āļ‚āļ­āļ‡ buprenorphine
  • āļāļēāļĢāđ€āļ‚้āļēāļ–ึāļ‡ OTP / āļ„āļĨิāļ™ิāļāļ—ี่āļˆ่āļēāļĒ methadone
  • āļ„āļ§āļēāļĄāļ•้āļ­āļ‡āļāļēāļĢāđ‚āļ„āļĢāļ‡āļŠāļĢ้āļēāļ‡āđāļĨāļ°āļāļēāļĢāļ”ูāđāļĨāđƒāļāļĨ้āļŠิāļ”āļ‚āļ­āļ‡āļ„āļ™āđ„āļ‚้

4.1 āļˆุāļ”āđ€āļ”่āļ™ buprenorphine

  • Partial agonist āđ€āļŠี่āļĒāļ‡ respiratory depression āđāļĨāļ° overdose āļ•่āļģāļāļ§่āļē
  • āđƒāļŠ้āđ„āļ”้āđƒāļ™ office-based practice (āđ„āļĄ่āļ•้āļ­āļ‡ OTP; āļ‚้āļ­āļāļģāļัāļš X-waiver āļ–ูāļāļĒāļāđ€āļĨิāļāđƒāļ™āļŠāļŦāļĢัāļ)
  • drug–drug interaction āļ™้āļ­āļĒāļāļ§่āļēāļĄัāļāļˆāļ°āļ›āļĨāļ­āļ”āļ ัāļĒāļāļ§่āļēāđƒāļ™āļœู้āļ›่āļ§āļĒ comorbidity āđ€āļĒāļ­āļ°
  • āđ€āļŦāļĄāļēāļ°āļัāļš:
    • moderate OUD
    • āļĄี access āļŦāļĄāļ­āļ—ี่āļŠั่āļ‡āļĒāļēāđ„āļ”้
    • āļĄีāđ‚āļ„āļĢāļ‡āļŠāļĢ้āļēāļ‡āļŠีāļ§ิāļ•āļžāļ­āļŠāļĄāļ„āļ§āļĢ (work, family support)

4.2 āļˆุāļ”āđ€āļ”่āļ™ methadone

  • Full agonist āđ€āļŦāļĄāļēāļ°āļัāļš:
    • high physical dependence (āđ€āļŠ่āļ™ āđƒāļŠ้ fentanyl, āđƒāļŠ้āļ‚āļ™āļēāļ”āļŠูāļ‡āļĄāļēāļ™āļēāļ™)
    • āđ€āļ„āļĒ fail āļŦāļĢืāļ­ divert buprenorphine
  • Retention āļ”ีāļāļ§่āļē buprenorphine (āļ­ัāļ•āļĢāļēāļ­āļĒู่āđƒāļ™āđ‚āļ›āļĢāđāļāļĢāļĄāļ™āļēāļ™āļāļ§่āļē)
  • āđƒāļŦ้āđƒāļ™ OTP āļĄีāđ‚āļ„āļĢāļ‡āļŠāļĢ้āļēāļ‡āļāļēāļĢāļ”ูāđāļĨ (frequent visit, support)

4.3 āļ‚้āļ­āļ„āļ§āļĢāļĢāļ°āļ§ัāļ‡

  • Methadone
    • QTc prolongation / torsade risk
    • lethal dose āļŠāļģāļŦāļĢัāļš opioid-naive āļ•่āļģ (~50 mg) diversion āļ­ัāļ™āļ•āļĢāļēāļĒ
  • Buprenorphine
    • partial agonist āđ€āļžāļ”āļēāļ™ effect āļ­āļēāļˆāđ„āļĄ่āļžāļ­āđƒāļ™āļ„āļ™āļ—ี่ dependence āļŠูāļ‡āļĄāļēāļ

5. Psychosocial Interventions

āđāļ™āļ§āļ—āļēāļ‡

  • āđāļ™āļ°āļ™āļģ” āđƒāļŦ้āļ—ุāļāļ„āļ™āļĄี psychosocial service āļĢ่āļ§āļĄ MOUD āđāļ•่āđ„āļĄ่ “āļšัāļ‡āļ„ัāļšāļŦāļĒุāļ”āļĒāļē” āļŦāļēāļāđ„āļĄ่āļĢ่āļ§āļĄ
  • āļ›āļĢāļ°āđ€āļ āļ—āļ—ี่āđƒāļŠ้:
    • CBT
    • Motivational interviewing
    • Contingency management
    • Family therapy
    • SUD counseling, peer support, housing case management āļŊāļĨāļŊ

āļŦāļĨัāļāļāļēāļ™

  • āļ‡āļēāļ™āļ§ิāļˆัāļĒ “āļœāļŠāļĄ” āļšāļēāļ‡āļŠุāļ”āđ„āļĄ่āļžāļš benefit āļŠัāļ”
  • meta-analysis āļŦāļĨāļēāļĒāļ‡āļēāļ™āļžāļšāļ§่āļē adjunct psychosocial:
    • āļĨāļ” dropout
    • āļĨāļ” illicit opioid use āļĢāļ°āļŦāļ§่āļēāļ‡āļĢัāļāļĐāļē
    • āļĨāļ” missed visits

āđƒāļŠ้āđāļ™āļ§āļ„ิāļ”:

  • āļ–้āļē āļ•āļ­āļšāļŠāļ™āļ­āļ‡āļĒāļēāđ„āļĄ่āļ”ี / partial response āđ€āļ™้āļ™āđ€āļžิ่āļĄ psychosocial
  • āļ–้āļēāļ—āļģāđ„āļ”้ āđƒāļŦ้āđ€āļĨืāļ­āļ intervention āļ„ุāļ“āļ āļēāļžāļŠูāļ‡ āđ€āļŠ่āļ™ contingency management, personalized psychosocial plan

6. Mild OUD (āđ„āļĄ่āļĄี physical dependence āļŠัāļ”āđ€āļˆāļ™)

  • āđāļ™āļ°āļ™āļģ opioid antagonist (āļ™ัāļĨāđ€āļ—āļĢāļāđ‚āļ‹āļ™) + psychosocial
    • LAI naltrexone monthly āđ€āļ›็āļ™āļ•ัāļ§āđ€āļĨืāļ­āļāļŦāļĨัāļ
    • oral naltrexone āđ€āļŦāļĄāļēāļ°āļัāļšāļ„āļ™āđ„āļ‚้ motivation āļŠูāļ‡ āđāļĨāļ°āļĄีāļāļēāļĢāļāļģāļัāļšāļāļēāļĢāļิāļ™āļĒāļē
  • āļ‚้āļ­āļ”ีāļ‚āļ­āļ‡ naltrexone āđƒāļ™ mild OUD:

1.                   āļšāļĨ็āļ­āļ„ mu receptor āđƒāļŠ้ opioid āļ‹้āļģāļ็ “āđ„āļĄ่āđ„āļ”้ high”

2.                   āđ„āļĄ่āļŠāļĢ้āļēāļ‡ physical dependence āđ€āļžิ่āļĄ (āļ–้āļēāļĒัāļ‡āđ„āļĄ่āļĄี)

3.                   āļ–้āļēāļ—āļ™āđ„āļĄ่āđ„āļ”้ āļŦāļĒุāļ”āđāļĨ้āļ§ switch āđ„āļ› methadone/buprenorphine āļ‡่āļēāļĒāļāļ§่āļē reverse direction


7. āļœู้āļ›่āļ§āļĒāļ—ี่āļ›āļิāđ€āļŠāļ˜āļĒāļē (MOUD)

  • āđ„āļĄ่āđāļ™āļ°āļ™āļģ āđƒāļŠ้ psychosocial alone āđ€āļ›็āļ™ first-line āđƒāļ™ moderate–severe OUD
  • āđāļ•่āđƒāļ™ mild OUD āļ—ี่āđ€āļĨืāļ­āļāđ€āļ­āļ‡, āļĄีāļ›āļĢāļ°āļ§ัāļ•ิ response āļ”ี, support strong psychosocial alone “āļ­āļēāļˆāļžิāļˆāļēāļĢāļ“āļēāđ„āļ”้”
  • āđƒāļŠ้ multimodal program:
    • weekly SUD counseling
    • mutual help groups (āđ€āļŠ่āļ™ NA) āļŦāļĨāļēāļĒāļ„āļĢั้āļ‡āļ•่āļ­āļŠัāļ›āļ”āļēāļŦ์
    • CBT / contingency management
  • āđ€āļ™้āļ™:
    • overdose prevention + naloxone
    • āļ„ุāļĒāđ€āļĢื่āļ­āļ‡ benefit āļ‚āļ­āļ‡ MOUD āļ•่āļ­āđ€āļ™ื่āļ­āļ‡ āđ€āļ›ิāļ”āđ‚āļ­āļāļēāļŠāđƒāļŦ้āđ€āļĢิ่āļĄāđƒāļ™āļ­āļ™āļēāļ„āļ•

8. Monitoring & Assessment of Response

8.1 āļāļēāļĢāļ•ิāļ”āļ•āļēāļĄ

  • Buprenorphine: āļŠ่āļ§āļ‡āđāļĢāļāļĄัāļ follow āļĢāļēāļĒāļŠัāļ›āļ”āļēāļŦ์ āđ€āļžื่āļ­āļ›āļĢัāļš dose
  • Methadone: āļŠāļēāļĄāļēāļĢāļ–āļ›āļĢāļ°āđ€āļĄิāļ™āļ–ี่āļāļ§่āļē (daily) āđƒāļ™ OTP
  • āļ—ุāļ visit:
    • āļ‹ัāļ substance use, craving, negative consequences
    • āļ›āļĢāļ°āđ€āļĄิāļ™ infection, pain, mental health
    • Urine drug screen āđ€āļ›็āļ™āļĢāļ°āļĒāļ°

8.2 āđ€āļāļ“āļ‘์āļ•āļ­āļšāļŠāļ™āļ­āļ‡

  • āđ€āļ›้āļēāļŦāļĄāļēāļĒāļŦāļĨัāļ:
    • abstinence 6 āđ€āļ”ืāļ­āļ™ āļˆāļēāļ illicit opioids
    • āđ„āļĄ่āļĄี heavy alcohol use
  • āļœāļĨāļ—ี่ “āļ–ืāļ­āļ§่āļēāļĒāļ­āļĄāļĢัāļšāđ„āļ”้” āđ€āļŠ่āļ™:
    • āļ­āļĒู่āđƒāļ™ treatment āļ•่āļ­āđ€āļ™ื่āļ­āļ‡āđāļĨāļ°āļิāļ™āļĒāļēāđ„āļ”้
    • āļĨāļ”āļ„āļ§āļēāļĄāļ–ี่āļāļēāļĢāđƒāļŠ้
    • āļĨāļ” craving
  • Failure signal:
    • urine āđāļ—āļšāļ—ุāļāļ„āļĢั้āļ‡ positive
    • āļ‚āļēāļ”āļ™ัāļ”āļš่āļ­āļĒ, diversion, āđ„āļĄ่āļิāļ™āļĒāļē

9. Management of Inadequate Response

āļ—ุāļāļ„āļ™

  • āđ€āļžิ่āļĄāļŦāļĢืāļ­āļ•่āļ­āļĒāļ­āļ” psychosocial (āđ€āļžิ่āļĄ frequency / āđ€āļžิ่āļĄ modality / āđ€āļžิ่āļĄāļĢāļ°āļ”ัāļš care residential āļŊāļĨāļŊ)

9.1 āļœู้āļ—ี่āļ­āļĒู่āļšāļ™ agonist (methadone / buprenorphine)

1.       Optimize dose āļ่āļ­āļ™ (āļĒัāļ‡āđƒāļŠ้āđāļĨ้āļ§ positive āđ€āļžิ่āļĄ dose)

2.       āļ–้āļēāđƒāļŠ้ daily buprenorphine āđāļĨ้āļ§āļĒัāļ‡āđ„āļĄ่āļ”ี:

o   āđ€āļĨืāļ­āļ methadone (āļ–้āļē dependence āļŠูāļ‡, āļ•้āļ­āļ‡āļāļēāļĢ agonism āļĄāļēāļ) āļŦāļĢืāļ­

o   LAI buprenorphine (āđāļ้āļ›ัāļāļŦāļē adherence)

3.       āļ–้āļē fail methadone & LAI buprenorphine:

o   āļžิāļˆāļēāļĢāļ“āļē LAI naltrexone āļŦāļĨัāļ‡ medically supervised withdrawal

4.       Switch āļĢāļ°āļŦāļ§่āļēāļ‡ methadone buprenorphine:

o   āļˆāļēāļ bup methadone āļ‡่āļēāļĒ (āđ€āļĢิ่āļĄ methadone āđ„āļ”้āđ€āļĨāļĒ)

o   āļˆāļēāļ methadone bup āļ•้āļ­āļ‡āđ€āļ§้āļ™āļŦāļĨāļēāļĒāļ§ัāļ™ (āļŦāļĢืāļ­āđƒāļŠ้ microdosing induction)

9.2 āļœู้āļ—ี่āđƒāļŠ้ antagonist (naltrexone)

  • Oral fail āļĨāļ­āļ‡ LAI naltrexone
  • Fail āļ—ั้āļ‡ oral + LAI āđ€āļ›āļĨี่āļĒāļ™āđ€āļ›็āļ™ buprenorphine āļŦāļĢืāļ­ methadone (āļ–้āļē dependence āļŠูāļ‡)

9.3 Psychosocial alone

  • āļ–้āļē 30 āļ§ัāļ™āđāļĨ้āļ§āļĒัāļ‡āđƒāļŠ้āļ‹้āļģāļ‹้āļ­āļ™ āđ€āļ™้āļ™āđ€āļžิ่āļĄ motivation āđƒāļŦ้āđ€āļĢิ่āļĄ MOUD
  • āļ–้āļēāļĒัāļ‡āļ›āļิāđ€āļŠāļ˜ āđ€āļžิ่āļĄ intensity āļ‚āļ­āļ‡ psychosocial (visit āļ–ี่āļ‚ึ้āļ™, āđ€āļžิ่āļĄ modality)

9.4 āļ›ัāļāļŦāļē adherence

  • āđƒāļŠ้ supervised dosing (āđ‚āļ”āļĒāļ„āļĢāļ­āļšāļ„āļĢัāļ§ / staff)
  • āļ–้āļē daily adherence āļĒัāļ‡āđāļĒ่ āđ€āļ›āļĨี่āļĒāļ™āđ€āļ›็āļ™ long-acting formulations
    • LAI naltrexone
    • LAI buprenorphine

10. Refractory Cases & Harm Reduction

  • āļĒัāļ‡āļ„āļ‡āđ€āļ™้āļ™ retention in treatment āđ€āļžāļĢāļēāļ°āļĨāļ” all-cause mortality āđāļĨāļ° overdose
  • āđƒāļŠ้:
    • long-acting meds
    • methadone dose āđ€āļŦāļĄāļēāļ°āđƒāļ™āļĢāļēāļĒ dependence āļŠูāļ‡
    • contingency management
    • case management + harm reduction
  • Harm reduction:
    • syringe services / safer use supplies
    • HIV/HCV testing & linkage
    • housing / social care navigation

āļšāļēāļ‡āļ›āļĢāļ°āđ€āļ—āļĻāļĄี heroin-assisted treatment āļŠāļģāļŦāļĢัāļšāļœู้āļ—ี่ fail āļ•āļĨāļ­āļ”āļˆāļēāļ methadone/bup āđāļ•่āļĒัāļ‡āđ€āļ›็āļ™āđ‚āļ›āļĢāđāļāļĢāļĄāđ€āļ‰āļžāļēāļ°āđāļĨāļ°āļĄีāļ‚้āļ­āļ–āļāđ€āļ–ีāļĒāļ‡āļŠูāļ‡


11. Duration of Therapy

  • āļĄāļ­āļ‡ OUD āđ€āļ›็āļ™ chronic, relapsing disease āđ€āļ™้āļ™ continuing care model
  • āđƒāļ„āļĢāļ—ี่ respond āļ”ี:
    • āļ–้āļēāļ•้āļ­āļ‡āļāļēāļĢāļ­āļĒู่āļšāļ™ MOUD āļ•่āļ­ āļŠāļ™ัāļšāļŠāļ™ุāļ™ “indefinite”
    • āļ–้āļēāļ•้āļ­āļ‡āļāļēāļĢāļŦāļĒุāļ”:
      • āļŦāļĨัāļ‡ free āļˆāļēāļāļāļēāļĢāđƒāļŠ้āļŠāļēāļĢ + āļŠีāļ§ิāļ•āļ„āļ‡āļ—ี่ (āļ‡āļēāļ™ āļ„āļ§āļēāļĄāļŠัāļĄāļžัāļ™āļ˜์) 6–12 āđ€āļ”ืāļ­āļ™
      • taper methadone/bup āļŠ้āļē āđ† āļŦāļĨāļēāļĒāđ€āļ”ืāļ­āļ™ (6 āđ€āļ”ืāļ­āļ™āļ‚ึ้āļ™āđ„āļ›)
      • naltrexone āļŦāļĒุāļ”āđ„āļ”้āđ€āļĨāļĒ
  • āļ–้āļēāđ€āļĢิ่āļĄ taper āđāļĨ้āļ§āļĄี craving/āđƒāļŠ้āļ‹้āļģ/āđ€āļ„āļĢีāļĒāļ”āļŦāļ™ัāļ āļŦāļĒุāļ” taper āđāļĨāļ°āļāļĨัāļšāđ„āļ› dose āļ่āļ­āļ™āļŦāļ™้āļē

12. Special Populations

12.1 āļŦāļĨัāļ‡ medically supervised withdrawal

  • first choice: LAI naltrexone + psychosocial
  • āļ–้āļēāđ€āļ„āļĒāļ•āļ­āļšāļŠāļ™āļ­āļ‡āļ”ีāļัāļš methadone/bup āļĄāļēāļ่āļ­āļ™ āđ€āļĨืāļ­āļāļ•āļēāļĄāļ›āļĢāļ°āļ§ัāļ•ิ
  • āļĢāļ°āļ§ัāļ‡: āļĨāļ” tolerance āđ€āļŠี่āļĒāļ‡ overdose āļ–้āļē relapse āļ”้āļ§āļĒ dose āđ€āļ”ิāļĄ

12.2 Pregnancy

  • First-line: methadone āļŦāļĢืāļ­ buprenorphine
  • āđ„āļĄ่āđāļ™āļ°āļ™āļģāđƒāļŦ้āđƒāļŠ้ naltrexone āļŦāļĢืāļ­ withdrawal alone āđ€āļ›็āļ™ first-line
  • āđ€āļ™้āļ™āļ”ูāđāļĨāđ€āļ‰āļžāļēāļ°āļ—āļēāļ‡ OB–Addiction

12.3 Hospitalized Patients

āļ–้āļēāļāļģāļĨัāļ‡āđ„āļ”้ MOUD āļ­āļĒู่āđāļĨ้āļ§

  • āļžāļĒāļēāļĒāļēāļĄ continue āđ€āļ”ิāļĄ
  • āļ–้āļēāļĒัāļ‡āļĒืāļ™āļĒัāļ™ dose āđ„āļĄ่āđ„āļ”้:
    • āđƒāļŦ้ methadone 30 mg āļŠั่āļ§āļ„āļĢāļēāļ§āđ€āļžื่āļ­āļัāļ™ withdrawal
    • buprenorphine āļ›āļĨāļ­āļ”āļ ัāļĒāļāļ§่āļēāđ€āļĢื่āļ­āļ‡ respiratory depression āļĄัāļāđƒāļŦ้āļ•āļēāļĄ dose āļ—ี่āļ„āļ™āđ„āļ‚้āļĢāļēāļĒāļ‡āļēāļ™āđ„āļ›āļ่āļ­āļ™

āļ–้āļēāđ€āļ›็āļ™ untreated OUD

  • admission āđ€āļ›็āļ™ “āđ‚āļ­āļāļēāļŠāļ—āļ­ā āđ€āļĢิ่āļĄ MOUD
    • initiation āđƒāļ™āđ‚āļĢāļ‡āļžāļĒāļēāļšāļēāļĨ + link to OPD/OTP āļĨāļ” illicit use, āļĨāļ” discharge against medical advice, āļĨāļ” readmission, āļĨāļ” overdose

12.4 QTc prolongation

  • QTc 500 ms āđ€āļĨี่āļĒāļ‡ methadone āđƒāļŠ้ buprenorphine āļŦāļĢืāļ­ naltrexone

12.5 Pain management

  • acute / chronic pain āđƒāļ™āļ„āļ™āđ„āļ‚้āļ—ี่āļĄี OUD āļŦāļĢืāļ­āļ­āļĒู่āļšāļ™ MOUD āļ•้āļ­āļ‡ consult āļŦāļĢืāļ­āđƒāļŠ้ protocol āđ€āļ‰āļžāļēāļ° (multimodal analgesia, adjustment methadone/bup)

12.6 Psychiatric comorbidities

  • āļĢัāļāļĐāļē OUD + psychiatric disorder āļžāļĢ้āļ­āļĄāļัāļ™
  • āđƒāļŠ้ care coordination; comorbidity āļ—ี่āļžāļšāļš่āļ­āļĒ: depression, anxiety, PTSD, personality disorders, insomnia, SUD āļ­ื่āļ™ āđ†

🧠 Opioid Use Disorder (OUD): Pharmacotherapy

🔎 Key Principles

  • OUD āđ€āļ›็āļ™ chronic relapsing illness āļ•้āļ­āļ‡āļāļēāļĢ long-term MOUD + psychosocial support
  • MOUD (Medication for OUD) = first-line treatment āļŠāļģāļŦāļĢัāļšāđāļ—āļšāļ—ุāļāļ„āļ™
  • āļ„āļ§āļĢāļ—āļģ shared decision-making āļšāļ™āļžื้āļ™āļāļēāļ™āļ„āļ§āļēāļĄāļĢุāļ™āđāļĢāļ‡āļ‚āļ­āļ‡āđ‚āļĢāļ„ āļāļēāļĢāļžึ่āļ‡āļžāļēāļĢ่āļēāļ‡āļāļēāļĒ (physical dependence) āļ›āļĢāļ°āļ§ัāļ•ิāļāļēāļĢāļĢัāļāļĐāļē drug availability āđāļĨāļ°āļ„āļ§āļēāļĄāļ•้āļ­āļ‡āļāļēāļĢāļ‚āļ­āļ‡āļœู้āļ›่āļ§āļĒ

1) Medication Choices (MOUD)

✔️ 1. Buprenorphine (Partial mu-agonist)

āđ€āļŦāļĄāļēāļ°āļัāļš:

  • OUD āļĢāļ°āļ”ัāļš moderate
  • āļœู้āļ›่āļ§āļĒāļ—ี่āđ€āļ‚้āļēāļ–ึāļ‡āļāļēāļĢāļĢัāļāļĐāļēāđƒāļ™āļ„āļĨิāļ™ิāļāļ—ั่āļ§āđ„āļ›āđ„āļ”้
  • āļœู้āļ—ี่āļĄีāļ„āļ§āļēāļĄāđ€āļŠี่āļĒāļ‡ overdose āļˆāļēāļ methadone
  • āļāļēāļĢāļĢัāļāļĐāļēāđƒāļ™ ED / inpatient / outpatient

Advantages

  • Lower overdose risk
  • Prescribed in office setting
  • Fewer drug interactions
  • āļĄี long-acting injectable (LAI) āļŠ่āļ§āļĒāđ€āļĢื่āļ­āļ‡ adherence

Formulations

  • Sublingual buprenorphine-naloxone most common
  • Buprenorphine monoproduct āļāļĢāļ“ีāđāļž้ naloxone (rare)
  • LAI formulations
    • Sublocade (monthly)
    • Brixadi (weekly/monthly)

Standard Induction

  • āđ€āļĢิ่āļĄāđ€āļĄื่āļ­āđ€āļ‚้āļēāļŠู่ mild–moderate withdrawal (COWS 5)
  • Day 1: 4 mg reassess āđ€āļžิ่āļĄāđ„āļ”้āļ–ึāļ‡ 8 mg
  • Day 2: total dose āļ‚āļ­āļ‡āļ§ัāļ™āđāļĢāļ āđ€āļžิ่āļĄāļˆāļ™āļ–ึāļ‡ 16 mg (āļ‚ึ้āļ™āļ–ึāļ‡ 24–32 mg āđƒāļ™ fentanyl users)
  • Maintenance: 8–16 mg/day (āļšāļēāļ‡āļĢāļēāļĒāļ•้āļ­āļ‡āļ–ึāļ‡ 24–32 mg/day)

Alternative Inductions

  • Microdosing (Bernese method): useful
    • fentanyl users
    • switching from methadone
    • cannot tolerate withdrawal
  • Aggressive ED induction: up to 32 mg safely under supervision

Adverse Effects

  • nausea, headache, constipation
  • Dental issues (important FDA warning) āđāļ™āļ°āļ™āļģāļš้āļ§āļ™āļ›āļēāļāļŦāļĨัāļ‡āđƒāļŠ้
  • Precipitated withdrawal (rare even with fentanyl)
  • No significant QTc prolongation

Tapering

  • Slow taper over months
  • āļĨāļ”āļ„āļĢั้āļ‡āļĨāļ° 2 mg āļ—ุāļ 1–2 āļŠัāļ›āļ”āļēāļŦ์
  • āļŦāļĒุāļ” taper āļŦāļēāļāļĄี craving āļŦāļĢืāļ­ withdrawal

✔️ 2. Methadone (Full agonist)

āđ€āļŦāļĄāļēāļ°āļัāļš:

  • Severe OUD
  • āļœู้āļ—ี่āđƒāļŠ้ fentanyl / high physical dependence
  • āļœู้āļ—ี่āļ•āļ­āļšāļŠāļ™āļ­āļ‡āđ„āļĄ่āļ”ีāļŦāļĢืāļ­ divert buprenorphine
  • āļœู้āļ—ี่āļ•้āļ­āļ‡āļāļēāļĢāđ‚āļ„āļĢāļ‡āļŠāļĢ้āļēāļ‡āļāļēāļĢāļĢัāļāļĐāļē (OTP clinic)

Advantages

  • Best retention in treatment
  • Effective for high-dependence patients
  • Stronger agonist suppresses cravings better

Initiation

  • Start: 20–30 mg
  • āđ€āļžิ่āļĄāļ—ีāļĨāļ° 5–10 mg āļ—ุāļ 2–3 āļ§ัāļ™
  • First-day max = 50 mg (US federal regulation)

Maintenance

  • Effective dose = 60–120 mg/day
  • Fentanyl users āļ­āļēāļˆāļ•้āļ­āļ‡āļĄāļēāļāļāļ§่āļē 120 mg
  • Higher doses better retention & suppression of heroin/fentanyl use

Rapid Initiation (Fentanyl era)

  • Inpatients: up to 60 mg day 1, up to 100 mg by day 7
  • Outpatients: 70 mg by day 7 higher retention

Safety Concerns

  • QTc prolongation torsade possible
  • ECG before start IF: cardiac history, QTc >450, QT-prolonging drugs
  • Avoid methadone if QTc 500 msec unless benefits outweigh risks
  • High overdose risk (especially with BZD/alcohol)
  • Hyperalgesia possible
  • Multiple CYP450 interactions

Taper

  • Very slow taper: āļĨāļ” ~5 mg/week āļŦāļĢืāļ­āļŠ้āļēāļāļ§่āļē
  • āļŦāļĒุāļ” taper āļŦāļēāļāđ€āļิāļ” craving/withdrawal

✔️ 3. Naltrexone (Opioid antagonist)

āđ€āļŦāļĄāļēāļ°āļัāļš:

  • Mild OUD
  • āļœู้āļ—ี่āđ„āļĄ่āļ•้āļ­āļ‡āļāļēāļĢ opioid agonist
  • āļœู้āļ—ี่āļ•้āļ­āļ‡āļāļēāļĢāļĒāļēāļ›้āļ­āļ‡āļัāļ™ "reinforcing effect" āļŦāļēāļāļāļĨัāļšāđ„āļ›āđƒāļŠ้
  • āļœู้āļ—ี่āļœ่āļēāļ™ medically supervised withdrawal āđāļĨ้āļ§

Important

  • āļ•้āļ­āļ‡ withdraw opioids 7–10 āļ§ัāļ™ āļ่āļ­āļ™āđ€āļĢิ่āļĄ
  • āđƒāļŠ้ naloxone challenge āļŦāļēāļāđ„āļĄ่āļĄั่āļ™āđƒāļˆāļ§่āļēāļœู้āļ›่āļ§āļĒ abstinent

Forms

1.       Extended-release injectable naltrexone (LAI) 380 mg IM q4 weeks

o   More effective than oral naltrexone

o   Better retention

2.       Oral naltrexone 50 mg/day

o   Low adherence

o   Effective only with supervision

o   Rare hepatotoxicity (dose-related)

When to use

  • āļœู้āļ›่āļ§āļĒāđ„āļĄ่āļĒāļ­āļĄāļĢัāļš agonist therapy
  • Mild OUD (no physical dependence)
  • āļœู้āļ›่āļ§āļĒāļŦāļĨัāļ‡ detox āļ—ี่āļ•้āļ­āļ‡āļ›้āļ­āļ‡āļัāļ™ relapse

Risks

  • Loss of opioid tolerance high overdose risk if relapse
  • Injection site reactions

2) Choosing MOUD: Practical Algorithm

Clinical Scenario

Recommended Treatment

Severe OUD / fentanyl / high physical dependence

Methadone first-line

Moderate OUD

Buprenorphine

Poor adherence to daily meds

Long-acting buprenorphine (Sublocade/Brixadi) OR LAI naltrexone

Mild OUD, no dependence

LAI naltrexone (preferred)

Failed buprenorphine

Methadone

Failed methadone

Buprenorphine (microdosing) or LAI naltrexone (after detox)

Patient refuses meds

Psychosocial only (not first-line) + overdose education + naloxone


3) Management of Inadequate Response

1.       Optimize dose

o   Buprenorphine up to 24–32 mg

o   Methadone >100 mg if needed

2.       Add psychosocial interventions

o   CBT, motivational interviewing, contingency management

3.       Switch agent

o   buprenorphine methadone

o   methadone microdose buprenorphine

o   antagonist agonist if relapse

4.       Use LAI formulations

o   adherence problems

5.       Consider social determinants

o   housing, case management, syringe services


4) Special Populations

✔️ Pregnancy

  • Methadone or buprenorphine (agonists) = preferred
  • Avoid naltrexone (limited RCT data, risk of withdrawal)

✔️ Hospitalized Patients

  • Continue existing MOUD
  • If untreated start MOUD inpatient
    • improves retention
    • reduces AMA discharge
    • reduces overdose risk

✔️ QTc prolongation

  • Avoid methadone if QTc 500
  • Prefer buprenorphine or naltrexone

✔️ Co-occurring psychiatric disorders

  • Treat both OUD + psychiatric disorder simultaneously

5) Key Evidence

  • MOUD reduces all-cause mortality by 50–70%
  • Methadone best retention
  • Buprenorphine less overdose risk
  • LAI naltrexone better than oral naltrexone
  • Psychosocial + MOUD best outcomes

6) Clinical Takeaways for ER & OPD

ðŸŸĒ If patient in withdrawal:

Start buprenorphine 4 mg titrate to 8–16 mg day 1

ðŸŸĒ If patient uses fentanyl:

Consider higher doses (16–32 mg), microdosing, or methadone

ðŸŸĒ If nonadherent:

Switch to LAI buprenorphine or LAI naltrexone

ðŸŸĒ Always give overdose education + naloxone


 

āđ„āļĄ่āļĄีāļ„āļ§āļēāļĄāļ„ิāļ”āđ€āļŦ็āļ™:

āđāļŠāļ”āļ‡āļ„āļ§āļēāļĄāļ„ิāļ”āđ€āļŦ็āļ™