Problematic opioid use meeting >=2 of 11 DSM-5-TR criteria in 12 months; high overdose mortality.
Also known as: OUD, opioid addiction, heroin use disorder, prescription opioid misuse
Overview
A pattern of opioid use leading to clinically significant impairment or distress, defined by >=2 of 11 DSM-5-TR criteria within 12 months. Tolerance and withdrawal in the context of appropriate medical use do not count toward criteria.
Epidemiology
~5 million people aged 12 or older with past-year OUD (NSDUH 2024: 4.8 million; modeled estimates are higher). Overdose deaths driven by fentanyl contamination of heroin and counterfeit pills. Disproportionate impact on rural communities and certain demographic groups.
Try two board-style Opioid Use Disorder questions
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Question 1PsychiatryMedium
A 34-year-old man who uses intranasal heroin daily wants to stop. He has cravings, withdrawal symptoms, and repeated unsuccessful attempts to cut down. Which of the following is the most appropriate medication-based treatment?
AMethadone taper for withdrawal
BAs-needed naloxone for overdose
CClonidine taper for withdrawal
DNaltrexone-bupropion combination
EBuprenorphine-naloxone maintenance
Reveal answer & full explanation
Correct answer: E — Buprenorphine-naloxone maintenance
AMethadone taper for withdrawal
BAs-needed naloxone for overdose
CClonidine taper for withdrawal
DNaltrexone-bupropion combination
EBuprenorphine-naloxone maintenance✓
Why Buprenorphine-naloxone maintenance is correct
Opioid use disorder is treated with maintenance agonist therapy: buprenorphine, methadone, or extended-release naltrexone.
Buprenorphine-naloxone curbs cravings and withdrawal while lowering overdose and illicit-use risk.
Long-term medication outperforms detoxification alone, which carries high relapse rates.
Why the others are wrong
Clonidine taper for withdrawal — Symptom-only trap: clonidine eases autonomic withdrawal but does not maintain remission or reduce relapse.
Naltrexone-bupropion combination — Right-drug-wrong-indication trap: this combination is for weight loss, and bupropion has no role in opioid use disorder.
As-needed naloxone for overdose — Right-tool-wrong-goal trap: take-home naloxone reverses overdose but is rescue therapy, not maintenance treatment.
Methadone taper for withdrawal — methadone is a first-line agonist for opioid use disorder, which makes this tempting, but used only as a short taper it is medically supervised withdrawal, and stopping the agonist after detoxification brings high relapse rates and a raised overdose risk from lost tolerance; methadone helps when continued as maintenance.
Question 2PsychiatryMedium
A 29-year-old with opioid use disorder requests medication and has moderate withdrawal symptoms now. Which of the following is the most appropriate therapy?
AOne-week buprenorphine-naloxone taper
BBuprenorphine-naloxone started now
CClonidine alone as definitive therapy
DScheduled alprazolam for the symptoms
EOral naltrexone started immediately now
Reveal answer & full explanation
Correct answer: B — Buprenorphine-naloxone started now
AOne-week buprenorphine-naloxone taper
BBuprenorphine-naloxone started now✓
CClonidine alone as definitive therapy
DScheduled alprazolam for the symptoms
EOral naltrexone started immediately now
Why Buprenorphine-naloxone started now is correct
Buprenorphine is a partial mu agonist whose induction is timed to begin once moderate withdrawal has emerged, exactly this patient's state.
Combining it with naloxone deters injection misuse.
Maintenance therapy lowers overdose mortality and improves retention versus withdrawal management alone.
Why the others are wrong
Oral naltrexone started immediately now — an antagonist given before full opioid clearance precipitates severe withdrawal; this is the right-drug-wrong-timing trap.
Scheduled alprazolam for the symptoms — benzodiazepines do not treat opioid use disorder and compound respiratory-depression risk; this is the symptom-sedation trap.
Clonidine alone as definitive therapy — clonidine only blunts autonomic withdrawal and does not reduce relapse or mortality; this is the adjunct-as-cure trap.
One-week buprenorphine-naloxone taper — it uses the right agent and would ease today's withdrawal, but brief withdrawal management without maintenance has high relapse rates and leaves the patient at heightened overdose risk once tolerance falls; this is the detox-instead-of-maintenance trap.
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Concurrent benzodiazepine or alcohol use (markedly raises overdose risk)
Pathophysiology
Mu-opioid receptor agonism produces analgesia, euphoria, and respiratory depression. Chronic exposure leads to receptor desensitization, upregulated cAMP signaling, and noradrenergic adaptation in locus coeruleus — basis for withdrawal phenomena.
Clinical presentation
Symptoms
Intoxication: euphoria, miosis, drowsiness, slurred speech, hypoventilation, decreased GI motility
Withdrawal: dysphoria, lacrimation, rhinorrhea, yawning, piloerection, mydriasis, myalgias, GI distress, autonomic hyperactivity — uncomfortable but rarely life-threatening in adults (dangerous in neonates and frail)
Sepsis, hypoglycemia, intracranial pathology — Differential for altered mental status — do not anchor on suspected overdose
Diagnostic workup
Diagnostic criteria
DSM-5-TR: A problematic pattern of opioid use causing impairment/distress, with >=2 of 11 criteria in 12 months. Tolerance/withdrawal under appropriately supervised opioid therapy do not count. Severity by criterion count as in other SUDs.
Labs
Urine drug screen (note: synthetic opioids including fentanyl and methadone require specific testing)
Hepatitis B/C, HIV, syphilis screening
CBC, CMP
Pregnancy test
ECG if methadone use (QT prolongation)
Imaging
TTE if endocarditis suspected
CT head for trauma/altered mental status
Diagnostic algorithm
MOUD
Mechanism
Setting
Key caveat
Buprenorphine
Partial mu agonist
Office-based
Precipitated withdrawal if started too early
Methadone
Full mu agonist
OTP only
QT prolongation; preferred for high tolerance
Naltrexone XR
Mu antagonist
Office-based
Requires 7-10 day opioid-free interval
FDA-approved medications for opioid use disorder.
Treatment
First-line
Medications for OUD (MOUD) — first-line and lifesaving: buprenorphine (partial mu agonist; sublingual film/tablet or monthly SC injection sublocade), methadone (full mu agonist; opioid treatment program only), or naltrexone XR (mu antagonist; requires opioid-free interval)
Buprenorphine can now be prescribed by any DEA-registered clinician (X-waiver eliminated 2023 MAT Act) — induce when patient in moderate withdrawal (COWS >=8-12) to avoid precipitated withdrawal
Methadone reduces all-cause mortality and is preferred for high-tolerance patients or those who fail buprenorphine; in pregnancy methadone and buprenorphine are both first-line
Counseling, contingency management, peer support (NA, SMART Recovery)
Naloxone distribution to patient and household — IM/IN, repeat as needed
Harm reduction: syringe service programs, fentanyl test strips, never use alone
Overdose
ABC, ventilatory support
Naloxone 0.4-2 mg IV/IM or 4 mg intranasal (in opioid-dependent patients who are still breathing, start 0.04-0.1 mg IV and titrate); repeat every 2-3 min; titrate to respiratory effort
Observe for resedation — fentanyl/methadone may require infusion or repeated doses
Refer to MOUD before discharge
Pregnancy
Buprenorphine (mono-product or buprenorphine/naloxone; do not switch a stable patient) or methadone, both first-line (buprenorphine is associated with less severe neonatal withdrawal) — withdrawal is harmful to fetus
Avoid medication-free detoxification
Coordinate prenatal care, monitor for neonatal abstinence syndrome
Breastfeeding compatible with both medications
Second-line / adjunct
Naltrexone XR 380 mg IM monthly — requires 7-10 day opioid-free interval; lower retention than agonist therapy
Inpatient detoxification only as bridge to MOUD (high relapse and overdose risk after detox alone)
Adjuncts for withdrawal: clonidine, lofexidine, loperamide, NSAIDs, ondansetron
Complications
Overdose death — leading cause of accidental death in US adults
Infectious: bacterial endocarditis, skin abscesses, osteomyelitis, HIV, hepatitis C
Incarceration, family disruption, financial collapse
PANCE pearls
MOUD reduces all-cause mortality by ~50% — buprenorphine and methadone are first-line; do not withhold.
Buprenorphine ceiling effect on respiratory depression makes it safer than methadone, but precipitated withdrawal can occur if initiated before adequate withdrawal (COWS >=8-12) — use 'micro-induction' for fentanyl-using patients.
Stigma is a barrier to MOUD — avoid terms like 'addict,' 'clean,' 'dirty urine.'
Co-prescribe and distribute naloxone for all patients on chronic opioids, MOUD, or with OUD history; train family/peers.
Methadone: ECG for QTc at baseline, 30 days, annually; avoid combining with QT-prolonging drugs.
References
SAMHSA TIP 63 — SAMHSA TIP 63: Medications for Opioid Use Disorder (2021)
ASAM 2020 — American Society of Addiction Medicine National Practice Guideline for the Treatment of Opioid Use Disorder (2020)
USPSTF 2020 — Screening for Unhealthy Drug Use: USPSTF Recommendation Statement. JAMA 2020
DSM-5-TR — American Psychiatric Association. DSM-5-TR (2022)
ACOG 2017 — ACOG Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy. Obstet Gynecol. 2017;130(2):e81-e94
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