ðĐš Opioid Use Disorder (OUD)
ð Introduction
- OUD =
chronic relapsing illness āļāļēāļ misuse āļāļāļ
opioids (prescribed, diverted āļŦāļĢืāļ illicit āđāļ่āļ heroin, fentanyl)
- āļŠ่āļāļāļĨ morbidity āđāļĨāļ° mortality āļŠูāļāļĄāļēāļ (overdose, infection, trauma)
- Treatment
goals = reduce relapse →
options: methadone, buprenorphine, naltrexone āđāļĨāļ° psychosocial
interventions
ð Epidemiology
- Epidemic
āļั้āļāđāļ่ 1990s āļั้āļ illicit āđāļĨāļ° prescribed opioids
- Synthetic
opioid overdose (fentanyl) āđāļิ่āļĄāļึ้āļāļ่āļāđāļื่āļāļ
- āļู้āļ่āļ§āļĒ OUD āļāļģāļāļ§āļāļĄāļēāļāđāļĢิ่āļĄāļāļēāļ misuse
prescription opioids
- Pregnant
OUD āđāļิ่āļĄāļึ้āļ → neonatal abstinence syndrome āđāļิ่āļĄ
Risk factors
- Personal/substance
use history
- Younger
age
- Chronic
pain with opioid therapy
- Mental
disorders
- Childhood
abuse/neglect
ðĐđ Practical
Recommendations for Safe Prescribing
ðŊ āđāļ้ multimodal
analgesia first
→ Opioids āđāļ็āļ
adjunct āđāļ่āļēāļั้āļ
|
Clinical Strategy |
Rationale |
|
āđāļ้ lowest
effective dose |
āļĨāļ tolerance/misuse |
|
āļĢāļ°āļĒāļ°āļŠั้āļāļี่āļŠุāļ (≤3
āļ§ัāļ āđāļŦāļĄāļēāļ°āļŠāļĄāļี่āļŠุāļ, ≤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: āđāļĄ้āļูāļāļĄāļāļāļ§่āļē mild āđāļ่āļ้āļāļĄูāļĨāļŦāļĨāļēāļĒāļุāļāļี้āļ§่āļē Risk persistent use āļŠูāļāļāļ§่āļē
immediate-release opioids āļื่āļāđ
⚙️ 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
ð§⚕️ 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
ð 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 ↑ āļāļĒ่āļēāļāļัāļāđāļāļ
- Trauma:
MVAs, falls → fracture
risk ↑ (esp. early in
treatment)
- Cancer
risk ↑ (related
exposures: hepatitis, smoking)
ð Disease Course
- ~50%
of heroin users develop OUD
- āļู้āđāļ้ opioid analgesics →
10–20% āļัāļāļāļēāđāļ็āļ OUD
- High
relapse rate āļŦāļēāļāđāļĄ่āļĄี maintenance therapy
ð§Š Screening &
Assessment
āđāļāļ°āļāļģāļัāļāļāļĢāļāļ āđāļāļู้āļ่āļ§āļĒāļี่āļĄี
risk āļŦāļĢืāļ evidence āļāļāļ opioid
misuse
āļัāļ§ screening tools:
- RODS
(8 items)
- OWLS
(4 items, āļŠāļģāļŦāļĢัāļ long-term opioid Rx)
History
- Substances
used, route (IV risk āļŠูāļāļŠุāļ), tolerance, last use
- Spending
behavior → āļāļ§āļēāļĄāļĢุāļāđāļĢāļāļāļāļ 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 →
āļ้āļāļāļāļĢāļ§āļāđāļāļāļēāļ°
- Infection
screening: HIV, Hep A/B/C, syphilis, TB
- CBC,
LFTs
Prescription Monitoring Program → āļ้āļāļāļัāļ doctor
shopping
ð§ Diagnosis (DSM-5-TR)
OUD = ≥2/11 criteria āļ āļēāļĒāđāļ 12
āđāļืāļāļ
āđāļ่āļāđāļ็āļ mild (2–3), moderate (4–5), severe (≥6)
(āđāļ้ table DSM-5-TR OUD criteria āđāļāļāļēāļĢāļ§ิāļิāļāļัāļĒ)
āļŦāļĨัāļāļāļēāļĢāļāļģāļ่āļēāļĒ 4 āļāļĨุ่āļĄāļāļēāļāļēāļĢ:
1.
Loss of control
2.
Social impairment
3.
Risky use
4.
Pharmacologic: tolerance & withdrawal
ðĄ Key Clinical Takeaways
|
āļāļĢāļ°āđāļ็āļ |
āļ้āļāļāļ§āļĢāļĢู้ |
|
āļู้āļ่āļ§āļĒ OUD āļāļēāļĒāđāļāļัāļāļĢāļēāļŠูāļ |
overdose, trauma |
|
Rapid tolerance → āđāļ้āđāļื่āļāļัāļ withdrawal |
āļĄāļēāļāļāļ§่āļēāļ้āļāļāļāļēāļĢ euphoria |
|
Fentanyl āļāļģāļĨัāļāđāļ็āļāļัāļ§āļัāļ overdose
epidemic |
āļāļĢāļ§āļ urine āļ้āļāļāļŠั่āļāđāļāļāļēāļ° |
|
Maintenance treatment (methadone/buprenorphine) |
āļĨāļ mortality āđāļĨāļ° relapse āļāļĒ่āļēāļāļĄีāļัāļĒāļŠāļģāļัāļ |
|
Infection screening & vaccination |
āļŠāļģāļัāļāļĄāļēāļāđāļ IVDU |
Treatment for Opioid Use Disorder
(OUD)
1. āļŦāļĨัāļāļิāļāļั่āļ§āđāļ
- āļู้āļ่āļ§āļĒāļŠ่āļ§āļāđāļŦāļ่ (āļĢāļ§āļĄāļึāļāļāļāļี่āļ่āļēāļ medically supervised
withdrawal āđāļĨ้āļ§) āļĄัāļāļ้āļāļāļāļēāļĢ long-term
treatment āđāļื่āļāļĨāļāļāļēāļĢāļāļĨัāļāđāļāđāļ้āļ้āļģ (relapse)
- First-line
= āđāļ้āļĒāļē (Medication for OUD, MOUD) + adjunct
psychosocial treatment
- āļĒāļēāļี่āđāļ้: methadone, buprenorphine, naltrexone
(oral / LAI)
- āļāļēāļāļĢāļēāļĒāļāļēāļāđāļ้āđāļ่āļĒāļē āļŦāļĢืāļāđāļ่ psychosocial āļāļēāļĄāļ้āļāļāļģāļัāļāđāļĨāļ°āļāļ§āļēāļĄāļ้āļāļāļāļēāļĢāļู้āļ่āļ§āļĒ
2. āļ่āļāļāđāļĢิ่āļĄāļāļēāļĢāļĢัāļāļĐāļē
2.1 Shared decision-making
- āļāļิāļāļēāļĒāļัāļ§āđāļĨืāļāļ: methadone, buprenorphine, naltrexone,
psychosocial āļĨ้āļ§āļ āđ
- āđāļ้āļāļ§่āļē pharmacotherapy āļĨāļ mortality
āđāļĨāļ° relapse āļāļĒ่āļēāļāļัāļāđāļāļ
āđāļ่āđāļิāļāđāļāļāļēāļŠāđāļŦ้āļāļāđāļ้āđāļĨืāļāļāđāļāļ§āļāļēāļ
- āļāļāđāļ้āļี่ treatment āļāļĢāļāļัāļ “preference”
āļĄี outcome āļีāļāļ§่āļē
2.2 āļāļĢāļ°āđāļĄิāļāļāļ§āļēāļĄāļĢุāļāđāļĢāļ OUD
- āđāļ้ DSM-5-TR OUD criteria āđāļ่āļ mild
/ moderate / severe
- āđāļāļāļēāļāļāļิāļัāļิ āđāļ้āļ:
- āļĄี physical dependence āļŦāļĢืāļāđāļĄ่
- āļ้āļēāļĄี tolerance āļัāļ + withdrawal āļัāļ → āļืāļāđāļ็āļ moderate–severe OUD
- DSM-5-TR
opioid withdrawal = ≥3 āđāļāļāļĨุ่āļĄāļāļēāļāļēāļĢ:
- dysphoric
mood, N/V, muscle aches, lacrimation/rhinorrhea, pupillary
dilation/piloerection/sweating, diarrhea, yawning, fever, insomnia
- āļāļĢāļ°āđāļĄิāļāđāļŠāļĄāļāļ§่āļē āļĢāļ°āļัāļ physical dependence āļŠูāļāđāļ่āđāļŦāļ (āđāļ่āļ āđāļ้ fentanyl āļāļāļēāļāļŠูāļ)
2.3 Education & overdose prevention
- āđāļŦ้ education āđāļĢื่āļāļ overdose +
āđāļāļ naloxone āđāļŦ้āļู้āļ่āļ§āļĒ/āļāļĢāļāļāļāļĢัāļ§
- āļĒิ่āļāļŠāļģāļัāļāđāļāļู้āļี่ āđāļĄ่āđāļ้ MOUD → āđāļŠี่āļĒāļ overdose
āļŠูāļāļāļ§่āļē
3. Initial Treatment Strategy
3.1 āļāļĨุ่āļĄāļĄี physical dependence
(moderate–severe OUD)
āđāļāļ§āļāļēāļāļี่āđāļāļ°āļāļģ
- āđāļŦ้ pharmacotherapy + psychosocial intervention
- āļีāļāļ§่āļē MOUD alone āļŦāļĢืāļ psychosocial
alone
āđāļŦāļุāļāļĨāđāļŦ้ MOUD āđāļ็āļ first-line
- āļĨāļ relapse
- āđāļิ่āļĄ retention
- āļĨāļ all-cause mortality & suicide
3.2 āđāļĨืāļāļāļĒāļē – agonist vs antagonist
āļāļģāđāļĄāļึāļ prefer agonist (methadone /
buprenorphine) > naltrexone
1.
āļĨāļ mortality āđāļ้āļัāļāđāļāļ
o meta-analysis:
āļ่āļ§āļāļี่āđāļ้āļĢัāļ opioid agonist → mortality āļĨāļāļĨāļāđāļืāļāļāļāļĢึ่āļāđāļีāļĒāļāļัāļāđāļĄ่āđāļ้āļĢัāļāļĐāļē
2.
āđāļĄ่āļ้āļāļāļĢāļāļāļāļāļĒāļēāđāļ็āļĄāļี่āļ่āļāļāđāļĢิ่āļĄ
o āđāļĢิ่āļĄ methadone/buprenorphine āđāļ้āđāļĄ้āļĒัāļāđāļ้ opioid
āļāļĒู่
o āđāļ่ naltrexone āļ้āļāļāļ่āļēāļ withdrawal āđāļ็āļĄ āđ 7–10 āļ§ัāļ → āļĒāļēāļāđāļ real
world, induction fail āļŠูāļ
3.
Outcome
o āļู้āļี่ “induce LAI naltrexone āđāļĄ่āļŠāļģāđāļĢ็āļ” relapse
āđāļĢ็āļ§
o āļ้āļēāļ่āļēāļ induction āđāļ้āđāļĨ้āļ§ → LAI
naltrexone efficacy āđāļāļĨ้āđāļีāļĒāļ buprenorphine
4. āļāļēāļĢāđāļĨืāļāļāļĢāļ°āļŦāļ§่āļēāļ Buprenorphine vs
Methadone
āļŦāļĨัāļāđāļ้āđāļĨืāļāļ
- āļĢāļ°āļัāļ dependence (āđāļāļĒāđāļāļāļēāļ° fentanyl/high-potency
use)
- āļāļĢāļ°āļ§ัāļิ response āļ่āļāļāļēāļĢāļĢัāļāļĐāļēāđāļิāļĄ
- āđāļāļāļēāļŠāļāļēāļĢ misuse/diversion āļāļāļ buprenorphine
- āļāļēāļĢāđāļ้āļēāļึāļ OTP / āļāļĨิāļิāļāļี่āļ่āļēāļĒ methadone
- āļāļ§āļēāļĄāļ้āļāļāļāļēāļĢāđāļāļĢāļāļŠāļĢ้āļēāļāđāļĨāļ°āļāļēāļĢāļูāđāļĨāđāļāļĨ้āļิāļāļāļāļāļāļāđāļ้
4.1 āļุāļāđāļ่āļ buprenorphine
- Partial
agonist → āđāļŠี่āļĒāļ respiratory depression āđāļĨāļ° overdose
āļ่āļģāļāļ§่āļē
- āđāļ้āđāļ้āđāļ office-based practice (āđāļĄ่āļ้āļāļ
OTP; āļ้āļāļāļģāļัāļ X-waiver āļูāļāļĒāļāđāļĨิāļāđāļāļŠāļŦāļĢัāļ)
- drug–drug
interaction āļ้āļāļĒāļāļ§่āļēāļĄัāļāļāļ°āļāļĨāļāļāļ ัāļĒāļāļ§่āļēāđāļāļู้āļ่āļ§āļĒ comorbidity
āđāļĒāļāļ°
- āđāļŦāļĄāļēāļ°āļัāļ:
- moderate
OUD
- āļĄี access āļŦāļĄāļāļี่āļŠั่āļāļĒāļēāđāļ้
- āļĄีāđāļāļĢāļāļŠāļĢ้āļēāļāļีāļ§ิāļāļāļāļŠāļĄāļāļ§āļĢ (work, family support)
4.2 āļุāļāđāļ่āļ methadone
- Full
agonist → āđāļŦāļĄāļēāļ°āļัāļ:
- high
physical dependence (āđāļ่āļ āđāļ้ fentanyl, āđāļ้āļāļāļēāļāļŠูāļāļĄāļēāļāļēāļ)
- āđāļāļĒ fail āļŦāļĢืāļ divert buprenorphine
- Retention
āļีāļāļ§่āļē buprenorphine (āļัāļāļĢāļēāļāļĒู่āđāļāđāļāļĢāđāļāļĢāļĄāļāļēāļāļāļ§่āļē)
- āđāļŦ้āđāļ OTP →
āļĄีāđāļāļĢāļāļŠāļĢ้āļēāļāļāļēāļĢāļูāđāļĨ (frequent visit, support)
4.3 āļ้āļāļāļ§āļĢāļĢāļ°āļ§ัāļ
- Methadone
- QTc
prolongation / torsade risk
- lethal
dose āļŠāļģāļŦāļĢัāļ opioid-naive āļ่āļģ (~50
mg) → diversion āļัāļāļāļĢāļēāļĒ
- Buprenorphine
- partial
agonist → āđāļāļāļēāļ effect āļāļēāļāđāļĄ่āļāļāđāļāļāļāļี่ dependence
āļŠูāļāļĄāļēāļ
5. Psychosocial Interventions
āđāļāļ§āļāļēāļ
- “āđāļāļ°āļāļģ” āđāļŦ้āļุāļāļāļāļĄี psychosocial service āļĢ่āļ§āļĄ MOUD
āđāļ่āđāļĄ่ “āļัāļāļัāļāļŦāļĒุāļāļĒāļē” āļŦāļēāļāđāļĄ่āļĢ่āļ§āļĄ
- āļāļĢāļ°āđāļ āļāļี่āđāļ้:
- CBT
- Motivational
interviewing
- Contingency
management
- Family
therapy
- SUD
counseling, peer support, housing case management āļŊāļĨāļŊ
āļŦāļĨัāļāļāļēāļ
- āļāļēāļāļ§ิāļัāļĒ “āļāļŠāļĄ” āļāļēāļāļุāļāđāļĄ่āļāļ benefit āļัāļ
- meta-analysis
āļŦāļĨāļēāļĒāļāļēāļāļāļāļ§่āļē adjunct psychosocial:
- āļĨāļ dropout
- āļĨāļ illicit opioid use āļĢāļ°āļŦāļ§่āļēāļāļĢัāļāļĐāļē
- āļĨāļ missed visits
āđāļ้āđāļāļ§āļิāļ:
- āļ้āļē āļāļāļāļŠāļāļāļāļĒāļēāđāļĄ่āļี / partial response → āđāļ้āļāđāļิ่āļĄ psychosocial
- āļ้āļēāļāļģāđāļ้ āđāļŦ้āđāļĨืāļāļ intervention āļุāļāļ āļēāļāļŠูāļ āđāļ่āļ
contingency management, personalized psychosocial plan
6. Mild OUD (āđāļĄ่āļĄี physical
dependence āļัāļāđāļāļ)
- āđāļāļ°āļāļģ opioid antagonist (āļัāļĨāđāļāļĢāļāđāļāļ)
+ psychosocial
- LAI
naltrexone monthly āđāļ็āļāļัāļ§āđāļĨืāļāļāļŦāļĨัāļ
- oral
naltrexone āđāļŦāļĄāļēāļ°āļัāļāļāļāđāļ้ motivation āļŠูāļ āđāļĨāļ°āļĄีāļāļēāļĢāļāļģāļัāļāļāļēāļĢāļิāļāļĒāļē
- āļ้āļāļีāļāļāļ naltrexone āđāļ mild OUD:
1.
āļāļĨ็āļāļ mu receptor → āđāļ้ opioid
āļ้āļģāļ็ “āđāļĄ่āđāļ้ high”
2.
āđāļĄ่āļŠāļĢ้āļēāļ physical
dependence āđāļิ่āļĄ (āļ้āļēāļĒัāļāđāļĄ่āļĄี)
3.
āļ้āļēāļāļāđāļĄ่āđāļ้ → āļŦāļĒุāļāđāļĨ้āļ§ switch
āđāļ methadone/buprenorphine āļ่āļēāļĒāļāļ§่āļē reverse
direction
7. āļู้āļ่āļ§āļĒāļี่āļāļิāđāļŠāļāļĒāļē (MOUD)
- āđāļĄ่āđāļāļ°āļāļģ āđāļ้ psychosocial alone āđāļ็āļ first-line āđāļ moderate–severe OUD
- āđāļ่āđāļ mild OUD āļี่āđāļĨืāļāļāđāļāļ, āļĄีāļāļĢāļ°āļ§ัāļิ response āļี, support strong
→ psychosocial alone “āļāļēāļāļิāļāļēāļĢāļāļēāđāļ้”
- āđāļ้ multimodal program:
- weekly
SUD counseling
- mutual
help groups (āđāļ่āļ NA) āļŦāļĨāļēāļĒāļāļĢั้āļāļ่āļāļŠัāļāļāļēāļŦ์
- CBT
/ contingency management
- āđāļ้āļ:
- overdose
prevention + naloxone
- āļุāļĒāđāļĢื่āļāļ benefit āļāļāļ MOUD āļ่āļāđāļื่āļāļ āđāļิāļāđāļāļāļēāļŠāđāļŦ้āđāļĢิ่āļĄāđāļāļāļāļēāļāļ
8. Monitoring & Assessment of Response
8.1 āļāļēāļĢāļิāļāļāļēāļĄ
- Buprenorphine:
āļ่āļ§āļāđāļĢāļāļĄัāļ follow āļĢāļēāļĒāļŠัāļāļāļēāļŦ์ āđāļื่āļāļāļĢัāļ dose
- Methadone:
āļŠāļēāļĄāļēāļĢāļāļāļĢāļ°āđāļĄิāļāļี่āļāļ§่āļē (daily) āđāļ OTP
- āļุāļ visit:
- āļัāļ substance use, craving, negative consequences
- āļāļĢāļ°āđāļĄิāļ infection, pain, mental health
- Urine
drug screen āđāļ็āļāļĢāļ°āļĒāļ°
8.2 āđāļāļāļ์āļāļāļāļŠāļāļāļ
- āđāļ้āļēāļŦāļĄāļēāļĒāļŦāļĨัāļ:
- abstinence
≥6 āđāļืāļāļ āļāļēāļ
illicit opioids
- āđāļĄ่āļĄี heavy alcohol use
- āļāļĨāļี่ “āļืāļāļ§่āļēāļĒāļāļĄāļĢัāļāđāļ้” āđāļ่āļ:
- āļāļĒู่āđāļ treatment āļ่āļāđāļื่āļāļāđāļĨāļ°āļิāļāļĒāļēāđāļ้
- āļĨāļāļāļ§āļēāļĄāļี่āļāļēāļĢāđāļ้
- āļĨāļ craving
- Failure
signal:
- urine
āđāļāļāļุāļāļāļĢั้āļ positive
- āļāļēāļāļัāļāļ่āļāļĒ, diversion, āđāļĄ่āļิāļāļĒāļē
9. Management of Inadequate Response
āļุāļāļāļ
- āđāļิ่āļĄāļŦāļĢืāļāļ่āļāļĒāļāļ psychosocial (āđāļิ่āļĄ frequency
/ āđāļิ่āļĄ modality / āđāļิ่āļĄāļĢāļ°āļัāļ care
→ residential āļŊāļĨāļŊ)
9.1 āļู้āļี่āļāļĒู่āļāļ agonist (methadone
/ buprenorphine)
1.
Optimize dose āļ่āļāļ (āļĒัāļāđāļ้āđāļĨ้āļ§ positive →
āđāļิ่āļĄ dose)
2.
āļ้āļēāđāļ้ daily
buprenorphine āđāļĨ้āļ§āļĒัāļāđāļĄ่āļี:
o āđāļĨืāļāļ methadone (āļ้āļē dependence āļŠูāļ, āļ้āļāļāļāļēāļĢ agonism āļĄāļēāļ)
āļŦāļĢืāļ
o LAI
buprenorphine (āđāļ้āļัāļāļŦāļē adherence)
3.
āļ้āļē fail methadone &
LAI buprenorphine:
o āļิāļāļēāļĢāļāļē LAI naltrexone āļŦāļĨัāļ medically
supervised withdrawal
4.
Switch āļĢāļ°āļŦāļ§่āļēāļ methadone ↔ buprenorphine:
o āļāļēāļ bup →
methadone āļ่āļēāļĒ (āđāļĢิ่āļĄ methadone āđāļ้āđāļĨāļĒ)
o āļāļēāļ methadone →
bup āļ้āļāļāđāļ§้āļāļŦāļĨāļēāļĒāļ§ัāļ (āļŦāļĢืāļāđāļ้ microdosing induction)
9.2 āļู้āļี่āđāļ้ antagonist
(naltrexone)
- Oral
fail → āļĨāļāļ
LAI naltrexone
- Fail
āļั้āļ oral + LAI →
āđāļāļĨี่āļĒāļāđāļ็āļ buprenorphine āļŦāļĢืāļ methadone
(āļ้āļē dependence āļŠูāļ)
9.3 Psychosocial alone
- āļ้āļē 30 āļ§ัāļāđāļĨ้āļ§āļĒัāļāđāļ้āļ้āļģāļ้āļāļ → āđāļ้āļāđāļิ่āļĄ
motivation āđāļŦ้āđāļĢิ่āļĄ MOUD
- āļ้āļēāļĒัāļāļāļิāđāļŠāļ → āđāļิ่āļĄ intensity āļāļāļ psychosocial
(visit āļี่āļึ้āļ, āđāļิ่āļĄ modality)
9.4 āļัāļāļŦāļē adherence
- āđāļ้ supervised dosing (āđāļāļĒāļāļĢāļāļāļāļĢัāļ§ / staff)
- āļ้āļē daily adherence āļĒัāļāđāļĒ่ → āđāļāļĨี่āļĒāļāđāļ็āļ
long-acting formulations
- LAI
naltrexone
- LAI
buprenorphine
10. Refractory Cases & Harm Reduction
- āļĒัāļāļāļāđāļ้āļ retention in treatment āđāļāļĢāļēāļ°āļĨāļ
all-cause mortality āđāļĨāļ° overdose
- āđāļ้:
- long-acting
meds
- methadone
dose āđāļŦāļĄāļēāļ°āđāļāļĢāļēāļĒ dependence āļŠูāļ
- contingency
management
- case
management + harm reduction
- Harm
reduction:
- syringe
services / safer use supplies
- HIV/HCV
testing & linkage
- housing
/ social care navigation
āļāļēāļāļāļĢāļ°āđāļāļĻāļĄี heroin-assisted
treatment āļŠāļģāļŦāļĢัāļāļู้āļี่ fail āļāļĨāļāļāļāļēāļ methadone/bup
āđāļ่āļĒัāļāđāļ็āļāđāļāļĢāđāļāļĢāļĄāđāļāļāļēāļ°āđāļĨāļ°āļĄีāļ้āļāļāļāđāļีāļĒāļāļŠูāļ
11. Duration of Therapy
- āļĄāļāļ OUD āđāļ็āļ chronic, relapsing
disease → āđāļ้āļ continuing care model
- āđāļāļĢāļี่ respond āļี:
- āļ้āļēāļ้āļāļāļāļēāļĢāļāļĒู่āļāļ MOUD āļ่āļ → āļŠāļัāļāļŠāļุāļ
“indefinite”
- āļ้āļēāļ้āļāļāļāļēāļĢāļŦāļĒุāļ:
- āļŦāļĨัāļ free āļāļēāļāļāļēāļĢāđāļ้āļŠāļēāļĢ + āļีāļ§ิāļāļāļāļี่ (āļāļēāļ
āļāļ§āļēāļĄāļŠัāļĄāļัāļāļ์) ≥6–12 āđāļืāļāļ
- taper
methadone/bup āļ้āļē āđ āļŦāļĨāļēāļĒāđāļืāļāļ (≈6
āđāļืāļāļāļึ้āļāđāļ)
- naltrexone
āļŦāļĒุāļāđāļ้āđāļĨāļĒ
- āļ้āļēāđāļĢิ่āļĄ taper āđāļĨ้āļ§āļĄี craving/āđāļ้āļ้āļģ/āđāļāļĢีāļĒāļāļŦāļัāļ → āļŦāļĒุāļ taper āđāļĨāļ°āļāļĨัāļāđāļ dose āļ่āļāļāļŦāļ้āļē
12. Special Populations
12.1 āļŦāļĨัāļ medically supervised
withdrawal
- first
choice: LAI naltrexone + psychosocial
- āļ้āļēāđāļāļĒāļāļāļāļŠāļāļāļāļีāļัāļ methadone/bup āļĄāļēāļ่āļāļ → āđāļĨืāļāļāļāļēāļĄāļāļĢāļ°āļ§ัāļิ
- āļĢāļ°āļ§ัāļ: āļĨāļ tolerance → āđāļŠี่āļĒāļ overdose
āļ้āļē relapse āļ้āļ§āļĒ dose āđāļิāļĄ
12.2 Pregnancy
- First-line:
methadone āļŦāļĢืāļ buprenorphine
- āđāļĄ่āđāļāļ°āļāļģāđāļŦ้āđāļ้ naltrexone āļŦāļĢืāļ withdrawal
alone āđāļ็āļ first-line
- āđāļ้āļāļูāđāļĨāđāļāļāļēāļ°āļāļēāļ OB–Addiction
12.3 Hospitalized Patients
āļ้āļēāļāļģāļĨัāļāđāļ้ MOUD āļāļĒู่āđāļĨ้āļ§
- āļāļĒāļēāļĒāļēāļĄ continue āđāļิāļĄ
- āļ้āļēāļĒัāļāļĒืāļāļĒัāļ dose āđāļĄ่āđāļ้:
- āđāļŦ้ methadone 30 mg āļั่āļ§āļāļĢāļēāļ§āđāļื่āļāļัāļ withdrawal
- buprenorphine
āļāļĨāļāļāļ ัāļĒāļāļ§่āļēāđāļĢื่āļāļ respiratory depression → āļĄัāļāđāļŦ้āļāļēāļĄ dose
āļี่āļāļāđāļ้āļĢāļēāļĒāļāļēāļāđāļāļ่āļāļ
āļ้āļēāđāļ็āļ untreated OUD
- admission
āđāļ็āļ “āđāļāļāļēāļŠāļāļāļ” āđāļĢิ่āļĄ MOUD
- initiation
āđāļāđāļĢāļāļāļĒāļēāļāļēāļĨ + link to OPD/OTP → āļĨāļ illicit
use, āļĨāļ discharge against medical advice, āļĨāļ readmission, āļĨāļ overdose
12.4 QTc prolongation
- QTc ≥500
ms → āđāļĨี่āļĒāļ
methadone → āđāļ้ buprenorphine āļŦāļĢืāļ naltrexone
12.5 Pain management
- acute
/ chronic pain āđāļāļāļāđāļ้āļี่āļĄี OUD āļŦāļĢืāļāļāļĒู่āļāļ
MOUD → āļ้āļāļ consult āļŦāļĢืāļāđāļ้ protocol āđāļāļāļēāļ° (multimodal analgesia, adjustment methadone/bup)
12.6 Psychiatric comorbidities
- āļĢัāļāļĐāļē OUD + psychiatric disorder āļāļĢ้āļāļĄāļัāļ
- āđāļ้ care coordination; comorbidity āļี่āļāļāļ่āļāļĒ:
depression, anxiety, PTSD, personality disorders, insomnia, SUD āļื่āļ āđ
ð§ Opioid Use Disorder
(OUD): Pharmacotherapy
ð Key Principles
- OUD āđāļ็āļ chronic relapsing illness → āļ้āļāļāļāļēāļĢ long-term
MOUD + psychosocial support
- MOUD
(Medication for OUD) = first-line treatment āļŠāļģāļŦāļĢัāļāđāļāļāļุāļāļāļ
- āļāļ§āļĢāļāļģ shared decision-making āļāļāļื้āļāļāļēāļāļāļ§āļēāļĄāļĢุāļāđāļĢāļāļāļāļāđāļĢāļ
āļāļēāļĢāļึ่āļāļāļēāļĢ่āļēāļāļāļēāļĒ (physical dependence) āļāļĢāļ°āļ§ัāļิāļāļēāļĢāļĢัāļāļĐāļē
drug availability āđāļĨāļ°āļāļ§āļēāļĄāļ้āļāļāļāļēāļĢāļāļāļāļู้āļ่āļ§āļĒ
1) Medication Choices (MOUD)
✔️ 1. Buprenorphine (Partial
mu-agonist)
āđāļŦāļĄāļēāļ°āļัāļ:
- OUD āļĢāļ°āļัāļ moderate
- āļู้āļ่āļ§āļĒāļี่āđāļ้āļēāļึāļāļāļēāļĢāļĢัāļāļĐāļēāđāļāļāļĨิāļิāļāļั่āļ§āđāļāđāļ้
- āļู้āļี่āļĄีāļāļ§āļēāļĄāđāļŠี่āļĒāļ overdose āļāļēāļ methadone
- āļāļēāļĢāļĢัāļāļĐāļēāđāļ ED / inpatient / outpatient
✦ Advantages
- Lower
overdose risk
- Prescribed
in office setting
- Fewer
drug interactions
- āļĄี long-acting injectable (LAI) → āļ่āļ§āļĒāđāļĢื่āļāļ adherence
✦ Formulations
- Sublingual
buprenorphine-naloxone →
most common
- Buprenorphine
monoproduct → āļāļĢāļีāđāļ้ naloxone (rare)
- LAI
formulations
- Sublocade
(monthly)
- Brixadi
(weekly/monthly)
✦ Standard Induction
- āđāļĢิ่āļĄāđāļĄื่āļāđāļ้āļēāļŠู่ mild–moderate withdrawal (COWS ≥5)
- Day
1: 4 mg → reassess
→ āđāļิ่āļĄāđāļ้āļึāļ
8 mg
- Day
2: total dose āļāļāļāļ§ัāļāđāļĢāļ → āđāļิ่āļĄāļāļāļึāļ 16
mg (āļึ้āļāļึāļ 24–32 mg āđāļ fentanyl
users)
- Maintenance:
8–16 mg/day (āļāļēāļāļĢāļēāļĒāļ้āļāļāļึāļ 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) →
āđāļāļ°āļāļģāļ้āļ§āļāļāļēāļāļŦāļĨัāļāđāļ้
- Precipitated
withdrawal (rare even with fentanyl)
- No
significant QTc prolongation
✦ Tapering
- Slow
taper over months
- āļĨāļāļāļĢั้āļāļĨāļ° 2 mg āļุāļ 1–2 āļŠัāļāļāļēāļŦ์
- āļŦāļĒุāļ taper āļŦāļēāļāļĄี craving āļŦāļĢืāļ withdrawal
✔️ 2. Methadone (Full agonist)
āđāļŦāļĄāļēāļ°āļัāļ:
- Severe
OUD
- āļู้āļี่āđāļ้ fentanyl / high physical dependence
- āļู้āļี่āļāļāļāļŠāļāļāļāđāļĄ่āļีāļŦāļĢืāļ divert buprenorphine
- āļู้āļี่āļ้āļāļāļāļēāļĢāđāļāļĢāļāļŠāļĢ้āļēāļāļāļēāļĢāļĢัāļāļĐāļē (OTP clinic)
✦ Advantages
- Best
retention in treatment
- Effective
for high-dependence patients
- Stronger
agonist → suppresses
cravings better
✦ Initiation
- Start:
20–30 mg
- āđāļิ่āļĄāļีāļĨāļ° 5–10 mg āļุāļ 2–3 āļ§ัāļ
- First-day
max = 50 mg (US federal regulation)
✦ Maintenance
- Effective
dose = 60–120 mg/day
- Fentanyl
users āļāļēāļāļ้āļāļāļĄāļēāļāļāļ§่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 āļŦāļĢืāļāļ้āļēāļāļ§่āļē
- āļŦāļĒุāļ taper āļŦāļēāļāđāļิāļ craving/withdrawal
✔️ 3. Naltrexone (Opioid
antagonist)
āđāļŦāļĄāļēāļ°āļัāļ:
- Mild
OUD
- āļู้āļี่āđāļĄ่āļ้āļāļāļāļēāļĢ opioid agonist
- āļู้āļี่āļ้āļāļāļāļēāļĢāļĒāļēāļ้āļāļāļัāļ "reinforcing effect" āļŦāļēāļāļāļĨัāļāđāļāđāļ้
- āļู้āļี่āļ่āļēāļ medically supervised withdrawal āđāļĨ้āļ§
✦ Important
- āļ้āļāļ withdraw opioids 7–10 āļ§ัāļ āļ่āļāļāđāļĢิ่āļĄ
- āđāļ้ naloxone challenge āļŦāļēāļāđāļĄ่āļĄั่āļāđāļāļ§่āļēāļู้āļ่āļ§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
- āļู้āļ่āļ§āļĒāđāļĄ่āļĒāļāļĄāļĢัāļ agonist therapy
- Mild
OUD (no physical dependence)
- āļู้āļ่āļ§āļĒāļŦāļĨัāļ detox āļี่āļ้āļāļāļ้āļāļāļัāļ 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
ðĒ If patient in
withdrawal:
Start buprenorphine 4 mg →
titrate to 8–16 mg day 1
ðĒ If patient uses
fentanyl:
Consider higher doses (16–32 mg), microdosing, or methadone
ðĒ If nonadherent:
Switch to LAI buprenorphine or LAI naltrexone
ðĒ Always give overdose
education + naloxone
āđāļĄ่āļĄีāļāļ§āļēāļĄāļิāļāđāļŦ็āļ:
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