Opioid use disorder

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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 include: ^[3]
  • 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 ^[4][5]

• Opioids bind to μ-opioid receptors in the locus coeruleus → inhibition of cAMP → ↓ norepinephrine release
• ↑ Dopamine in mesolimbic reward circuits → euphoria

Long-term use ^[4][5]

Long-term opioid use leads to upregulation of the cAMP pathway (to offset inhibition resulting from opioids), resulting in:

• Tolerance
  • 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 ^[4]

• Hyperactivity in the locus coeruleus → excessive release of norepinephrine → OWS
• See “Pathophysiology” in “Opioid withdrawal” for details.

• Tolerance, dependence, craving, compulsive use
• Social impairment (e.g., unable to fulfill family, work, or school obligations)
• Opioid-induced disorders, e.g.:
  • Depressive disorder, anxiety disorder
  • Sleep disorders
  • Sexual dysfunction
  • Delirium
• Opioid-induced neurotoxicity
  • 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 ^[7]

• 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:
  • Increasingly larger amounts of opioids are needed to achieve the desired effect.
  • Effects are increasingly diminished with the use of the same amount of opioids.
• One or both of the following manifestations of withdrawal:
  • OWS
  • Use of opioids to relieve withdrawal symptoms

Interpretation

• 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.
• Severity
  • 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. ^[7]

• Unhealthy drug use
• Physical dependence
• Accidental misuse (resulting from, e.g., limited health literacy, dementia)
• Self-medication
  • Insomnia
  • Mood disorder
  • Pain
• Diversion of prescription for financial or other reasons

The differential diagnoses listed here are not exhaustive.

Approach ^[8]

• 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. ^[9]
• Refer to an addiction medicine specialist as needed.

OUD is a chronic disorder. Treatment aims to prevent relapse of unhealthy drug use. ^[6]

Do not withhold MOUD from patients who decline a psychosocial evaluation or if comprehensive addiction treatment is unavailable. ^[8]

Medication for opioid use disorder (MOUD) ^[6]

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

• Induction phase
  • The process of initiating MOUD to determine an effective treatment dose
  • See “Methadone induction” and “Buprenorphine induction” in “Opioid withdrawal.”
  • Induction regimens vary but are generally similar to those used to treat OWS.
  • See “Methadone induction” and “Buprenorphine induction” in “Opioid withdrawal” for dosages.
• Maintenance therapy
  • May require higher doses than the induction phase ^[6]
  • 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. ^[6]

Opioid antagonist therapy

• Indication: maintenance therapy for patients who have completed opioid withdrawal and want to abstain from opioid use
• Treatment options
  • 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. ^[8]

• 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. ^[4]
• Opioid overdose prevention
  • Provide take-home naloxone.
  • Advise patients to only use opioids in the company of others.
  • Recommend fentanyl testing strips (if available). ^[10][11]
• Relapse prevention
  • Proactively treat OWS.
  • Discuss cravings and triggers for use at follow-up appointments.
  • Treat comorbid conditions (e.g., chronic pain, depression).
  • Refer to social services as indicated.
• HIV prevention: Offer HIV PrEP to HIV-negative individuals who inject drugs. ^[12]
• Patient education
  • 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. ^[8]

• One-Minute Telegram 84-2023-2/3: Buprenorphine in the fentanyl era
• One-Minute Telegram 76-2023-1/3: Missed opportunities in the treatment of OUD

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