Opioid use disorder (OUD) is a chronic disease characterized by physical and psychological dependence on prescription and/or illicit opioids. The prevalence of OUD in the United States has risen sharply in recent decades. Core clinical features of OUD are a persistent pattern of maladaptive behaviors related to the pursuit and use of opioids, including use despite adverse consequences and a preoccupation with obtaining opioids. Diagnosis is based on DSM-5 criteria. Medication-assisted treatment is the cornerstone of management, combining medications for opioid use disorder (MOUD) with individualized psychosocial treatment. Long-acting opioid agonists (i.e., methadone or buprenorphine) are most commonly used and have comparable long-term outcomes for addressing cravings and opioid withdrawal syndrome (OWS) and reducing the risk of overdose. Naltrexone may be appropriate for patients trying to abstain from opioid use. OUD is a highly stigmatized lifelong condition that requires a strong therapeutic alliance and patient-centered approach to address relapses, comorbid conditions (e.g., PTSD, infectious complications of injecting drugs), and other circumstances that may impact treatment adherence.
- In the US:
- ∼ 3 million people have a current or past opioid use disorder (OUD).
- ∼ 17,000 deaths per year are related to opioid use.
- Global burden of disease: approx. 11 million disability-adjusted life years
Epidemiological data refers to the US, unless otherwise specified.
Risk factors for prescription opioid misuse 
- History of prior or current substance use disorders
- Family history of substance use disorders
- History of prior or current psychiatric disorders/mental health disorders (e.g., anxiety, depression)
- Severe pain
Opioid agonists bind at κ-, δ-, and μ-opioid receptors throughout the body. Clinical features of OUD (e.g., physical dependence and compulsive use) result from repeated stimulation of μ-opioid receptors in the brain.
Acute use 
- Opioids bind to μ-opioid receptors in the locus coeruleus → inhibition of cAMP → ↓ norepinephrine release
- ↑ Dopamine in mesolimbic reward circuits → euphoria
Long-term use 
Long-term opioid use leads to upregulation of the cAMP pathway (to offset inhibition resulting from opioids), resulting in:
- Ongoing stimulation of μ-opioid receptors is required to maintain normal levels of norepinephrine.
- Increasingly higher opioid doses are needed to achieve analgesic, euphoric, and sedative effects.
- Dependence: absent or diminished stimulation of μ-opioid receptors → ↑ norepinephrine levels → OWS
Opioid cessation 
- Hyperactivity in the locus coeruleus → excessive release of norepinephrine → OWS
- See “Pathophysiology” in “Opioid withdrawal” for details.
- Compulsive use
- Social impairment (e.g., unable to fulfill family, work, or school obligations)
- Opioid-induced disorders, e.g.:
- Acute delirium, myoclonus, hallucinations, and/or hyperalgesia
- Thought to result from the accumulation of active metabolites of morphine, hydromorphone, or hydrocodone
See “Management of substance use disorder” for screening recommendations. Utilize DSM-5 criteria based on clinical suspicion for OUD or for patients who screen positive for unhealthy drug use.
DSM-5 diagnostic criteria for opioid use disorder 
- Taking larger amounts of opioids and for longer than intended
- Inability to reduce opioid intake despite a desire to do so
- Spending excessive time obtaining, using, or recovering from opioids
- Craving or having a strong desire to use opioids
- Failing to fulfill family, work, or school obligations as a result of opioid use
- Continued use of opioids despite negative social or interpersonal consequences
- Stopping or limiting important social, work, or leisure activities as a result of opioid use
- Repeated opioid use in physically hazardous situations
- Continued opioid use despite knowledge of its personal harm (physical and/or psychological)
- One or both of the following manifestations of tolerance:
- One or both of the following manifestations of withdrawal:
- Use of opioids to relieve withdrawal symptoms
- OUD: ≥ 2 criteria occurring within a 12-month period
- Exceptions: Physical dependence (i.e., the presence of tolerance and/or withdrawal) is not considered a criterion in patients solely using opioids under appropriate medical supervision.
- Mild: 2–3 criteria
- Moderate: 4–5 criteria
- Severe: 6–7 criteria
The presence of tolerance and/or withdrawal alone is not sufficient to diagnose OUD in patients solely using opioids as prescribed under appropriate medical supervision. 
- Unhealthy drug use
- Physical dependence
- Accidental misuse (resulting from, e.g., limited health literacy, dementia)
- Diversion of prescription for financial or other reasons
The differential diagnoses listed here are not exhaustive.
- Identify and treat OWS.
- Perform a comprehensive SUD assessment.
- Offer medication-assisted treatment, i.e.:
- Medication for opioid use disorder (MOUD)
- Psychosocial treatment (e.g., cognitive behavioral therapy)
- Utilize person-centered language, motivational interviewing, and harm reduction strategies. 
- Refer to an addiction medicine specialist as needed.
OUD is a chronic disorder. Treatment aims to prevent relapse of unhealthy drug use. 
Do not withhold MOUD from patients who decline a psychosocial evaluation or if comprehensive addiction treatment is unavailable. 
Medication for opioid use disorder (MOUD) 
MOUD involves the treatment of OUD with a long-acting opioid agonist (i.e., methadone or buprenorphine) or antagonist (i.e., naltrexone). See “Management of opioid withdrawal” for details on initiating treatment for OWS.
- Higher success rates than abstinence-based treatment
- Initiate under medical supervision
- Continue for as long as the patient benefits from treatment.
Opioid agonist therapy
- The process of initiating MOUD to determine an effective treatment dose
- See “Methadone induction” and “Buprenorphine induction” in “Opioid withdrawal.”
- May require higher doses than the induction phase 
- Methadone: typically administered at a methadone clinic
- Buprenorphine: can be prescribed by any practitioner with a current DEA registration
Methadone and buprenorphine have comparable long-term efficacy and safety outcomes. 
Opioid antagonist therapy
- Indication: maintenance therapy for patients who have completed opioid withdrawal and want to abstain from opioid use
- Oral naltrexone
- IM naltrexone administered by a health care professional
To avoid precipitated withdrawal, ensure opioid abstinence for 7–14 days prior to starting naltrexone. 
- Opioid withdrawal syndrome
- Opioid overdose
- Infections in people who inject drugs (e.g., HIV, hepatitis C, endocarditis; , skin and soft tissue infections)
We list the most important complications. The selection is not exhaustive.
- Primary prevention: Early recognition and treatment of physical dependence may prevent the development of OUD. 
- Opioid overdose prevention
- Relapse prevention
- HIV prevention: Offer HIV PrEP to HIV-negative individuals who inject drugs. 
- Counseling on the use of prescription opioids
- Safe injection practices; needle exchange services
- Counseling on sexual health
Provide take-home naloxone kits to all patients with OUD and/or risk factors for opioid overdose. Train patients and close contacts in the use of naloxone for treating opioid overdose.