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 nonprescription 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 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 disorder (SUD)
  • Family history of SUD
  • 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

General principles ^[7]

• For suspected OUD (e.g., based on SUD screening), use the DSM-5 criteria for OUD to confirm diagnosis.
• If OUD diagnosis is confirmed, perform laboratory studies to:
  • Evaluate for complications of opioid use
  • Guide treatment

DSM-5 diagnostic criteria for OUD ^[8]

• 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. ^[8]

Laboratory studies ^[7]

• Urine drug testing: as part of an SUD assessment to guide treatment planning ^[7][9]
• Testing for bloodborne pathogens, i.e., HIV testing, hepatitis B screening, and hepatitis C screening
• Latent tuberculosis screening ^[10]
• CBC and liver chemistries: to assess for infection and liver dysfunction
• Pregnancy test
• STI screening ^[10]

• 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 ^[7]

• Identify and treat opioid withdrawal syndrome.
• Perform a comprehensive SUD assessment.
• Identify and treat concurrent substance use and psychiatric disorders.
• Offer or refer for medication-assisted treatment, i.e.:
  • Medication for opioid use disorder : ^[11]
  • Psychosocial treatment (e.g., cognitive behavioral therapy)
• Consider referral for inpatient or residential management for high-risk patients.
• Initiate strategies for harm reduction in OUD and discuss relapse prevention.

Use person-centered language to reduce stigma and engage patients. ^[12]

Do not withhold medication for opioid use disorder from patients who decline a psychosocial evaluation or if comprehensive addiction treatment is unavailable. ^[13]

Medication for OUD (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.

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

Opioid agonist therapy

• Induction phase
  • 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. ^[13]

Harm reduction in OUD ^[7][14]

• Educate patients on opioid overdose prevention, including:
  • Safe use strategies, e.g.:
    • Using opioids in the company of others and/or at a supervised injection facility ^[15]
    • Safe opioid storage
    • Use of fentanyl testing strips (if available) ^[16][17]
  • Naloxone prescription for opioid overdose reversal
• To reduce the risk of infections:
  • Offer hepatitis A vaccine and hepatitis B vaccine.
  • Counsel on STI prevention.
  • For individuals who inject drugs:
    • Educate on safe injection practices.
    • Provide safe injection supplies and/or refer to a syringe services program.
    • Offer HIV PrEP to patients with HIV PrEP indications.
• Counsel on contraception and offer long-acting reversible contraception to prevent unintended pregnancies. ^[18]

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. ^[7]

Relapse prevention ^[7]

• Identify and treat OWS symptoms.
• Follow up with patients regularly.
• Encourage patients to engage with psychosocial counseling.
• Optimize management of comorbid physical, psychiatric, and substance use disorders.
• Assist patients in identifying triggers for opioid use.
• Use maintenance therapy for OUD.

Opioid withdrawal management is not recommended without maintenance therapy for OUD because of the high risk of relapse. ^[7]

• 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.

• Carefully weigh the risks and benefits of opioid therapy and avoid unnecessary prescription of opioids. For details, see:
  • Choice of analgesic for acute pain
  • Management of chronic noncancer pain
• When prescribing opioids, follow principles of risk mitigation for opioid therapy. For details, see:
  • Opioids for acute pain
  • Opioids for chronic noncancer pain
• Include screening for SUD as part of routine health care.

OUD in pregnancy

Screening and diagnostics ^[18][20]

• Verbally screen all pregnant individuals for SUD during the first prenatal visit.
  • Prenatal psychosocial screening options include:
    • NIDA quick screen
    • CRAFFT
    • 4Ps Plus
  • Screening drug tests are generally not recommended; obtain informed consent before testing for any drug use in pregnancy. ^[9][21]
• Diagnostics for OUD are the same as in nonpregnant individuals.

State laws may mandate reporting of substance use during pregnancy. ^[7]

Management ^{[7][18][20][22]}

The following modifications to the general management of OUD are recommended.

Prenatal management ^[7][18][22]

Involve a multidisciplinary team to ensure the best outcomes for the patient and fetus.

• Educate patients about complications of untreated OUD in pregnancy.
• As part of harm reduction in OUD, encourage:
  • Use of naloxone in the event of overdose
  • Smoking cessation ^[7]
• Refer for treatment with an addiction specialist.
  • First-line: pharmacotherapy with opioid agonists (i.e., methadone and buprenorphine)
  • The safety of other opioid treatment options (e.g., medically supervised opioid withdrawal management, naltrexone) is unclear in pregnancy.
  • Consider hospitalization for the initiation of MOUD to reduce the risk of adverse events. ^[7]
• Provide additional tailored prenatal care as indicated, e.g.:
  • Third-trimester screening for STIs
  • Additional prenatal ultrasounds to assess for intrauterine growth retardation

Although opioid agonists can cause neonatal abstinence syndrome, they are the preferred treatment option in pregnancy because they have a lower risk of adverse maternal and fetal outcomes than untreated OUD. ^[7][18]

Peripartum management ^[18][22]

• Continue maintenance dose of opioid agonists throughout labor.
• Offer obstetric analgesia to all individuals.
  • Utilize multimodal pain relief, including regional analgesia, NSAIDs, and acetaminophen.
  • If opioids are used:
    • Higher doses are typically required because of opioid dependence.
    • Avoid butorphanol, nalbuphine, or pentazocine because of the risk of precipitating withdrawal.
• Monitor newborns closely after birth for signs of neonatal abstinence syndrome.

Postpartum management ^[7][18][23]

• Ensure patients are connected to appropriate support services, including relapse prevention.
• Educate patients on safe breastfeeding.
  • Patients can breastfeed if they: ^[18]
    • Are stable on opioid agonists
    • Have no contraindications to breastfeeding (e.g., active blood-borne infections)
    • Are not currently using recreational drugs or misusing prescription drugs
  • Advise patients to stop breastfeeding if they relapse.

Complications of untreated OUD in pregnancy ^[18]

• Disruptions to prenatal care
• Intrauterine growth restriction
• Placental abruption
• Preterm labor
• Intrauterine meconium passage
• Fetal death
• Low infant birth weight ^[22]
• Neonatal abstinence syndrome ^[18]

Prevention ^[18]

• Offer contraceptive counseling and initiation of long-acting reversible contraception for patients with OUD.
• Avoid prescribing opioids in pregnancy whenever possible.
• If opioids are required, e.g., for acute severe pain, discuss risks and benefits for the pregnant individual and fetus.
• For patients with chronic pain, refer to a pain specialist if there is concern for developing opioid tolerance. ^[21]

• 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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