Day # 163: Opioid Use Disorder
- Marcus Hunt
- Apr 13
- 7 min read
Today we will discuss opioid use disorder (OUD). OUD is a major public health crisis affecting individuals, families, and communities worldwide. Today's post includes an introduction, diagnostic criteria, epidemiology, pathogenesis, clinical pearls, management of intoxication and withdrawal, and treatment.
Today's Content Level: Intermediate
Opioids are a class of drugs that interact with opioid receptors in the brain to produce pain relief, euphoria, and sedation.
Prescription opioids are primarily used for moderate to severe pain control, though some may be used for cough suppression and diarrhea (in select cases).
Opioids may be taken by mouth, smoked, insufflated, or injected.
History:
Derived from the opium poppy, opioids have been used for millennia for their analgesic and euphoric properties. With the advent of synthetic opioids and potent derivatives, medical use expanded, but so did misuse and addiction.
The U.S. opioid epidemic was fueled by aggressive pain treatment campaigns in the 1990s, widespread OxyContin use, and illicit heroin/fentanyl surges in the 2010s.
Common Opioids:
Natural: Morphine, codeine
Semi-Synthetic: Dextromethorphan, oxycodone, hydrocodone, heroin (illicit)
Synthetic: Fentanyl, methadone, tramadol, meperidine
Mechanism of Action:
Receptor Binding: Opioids bind to mu (primarily), delta, and kappa opioid receptors in the central and peripheral nervous system.
Activation of mu receptors primarily leads to analgesia and euphoria while reducing pain signaling in the central nervous system.
Downstream Effects: Inhibition of substance P and other neurotransmitter release, leading to decreased perception of pain and sometimes respiratory depression. Opioids also increase dopamine release in the nucleus accumbens, which mediates their addictive and rewarding properties.
Diagnostic Criteria 3
Diagnostic criteria for all substance use disorders are the same, characterized by a ≥ 12-month period of problematic substance use that leads to impairment or distress and requires ≥2 additional criteria. See Day #160: Introduction to Substance Use Disorders for complete diagnostic criteria and severity specifiers.
Genetics, environmental influences, and mental health comorbidities contribute to vulnerability.
Prevalence: 10% of Americans reported some level of prescription opioid misuse in the past year. Around 3.7% needed OUD treatment. Opioid abuse is a major driver of overdose deaths (~80,000 in 2022 in the U.S.).
Gender: Men have slightly higher rates than women, however, women often have higher rates of prescription opioid use, and their trajectories in developing OUD may differ, sometimes showing more rapid progression.
Age: Highest rates in ages 18–29. Adolescents and older adults also warrant attention, as their patterns of misuse and risk factors differ significantly.
Genetics and Biology: Genetics, including the impact of one’s environment on gene expression, account for about 50% of a person’s risk. Chronic opioid use affects the mesolimbic dopamine system, leading to reinforcement and dependence.
Environmental Influences: Areas with high unemployment and poverty, regions with high availability of prescription opioids (e.g., less stringent prescribing practices), individuals with traumatic experiences, and peer/social influences increase risk.
Comorbidities: Often coexists with chronic pain, mood disorders, anxiety disorders, and other substance use disorders, complicating both the course and treatment.
History: Obtain a detailed history (onset, frequency, quantity, last use, forms and routes), prior treatment attempts, periods of sobriety, withdrawal symptoms, impact on daily functioning, social history with triggers, legal obligations, and co-occurring psychiatric or medical conditions. Ask about prescription misuse and illicit use. Ask about injection drug use, overdose history, co-use of benzos or alcohol. Check the prescription monitoring database if available. Assess for other safety concerns related to use, including IV/IN use, sharing paraphernalia, needle licking, exchanging sex for drugs, body packing/stuffing, or impaired driving. Behaviors such as losing medication, “doctor shopping,” and running out of medication early should alert clinicians of possible misuse.
Screen for polysubstance use, especially alcohol, benzodiazepines, or stimulants.
Screening questionnaires: ORT (Opioid Risk Tool), DAST (Drug Abuse Screening Test).
Physical exam:
Intoxication: ↓ mental status, ↓ respiratory rate and tidal volume, ↓ bowel sounds, constricted pupils (miosis) (confounded by co-ingestants), and other signs of recent use (track marks, abscesses, heart murmur, presence of fentanyl patches, injuries).
Meperidine (Demerol) is the exception to opioids producing miosis. Memorization trick: “Demerol Dilates pupils.”
Medical complications of use: abscess, cellulitis, osteomyelitis, endocarditis, sepsis, opioid-induced bowel syndrome, hyperalgesia syndrome, toxic leukoencephalopathy with inhaled vapor, rhabdomyolysis, compartment syndrome.
Labs/Diagnostics:
Urine drug screen → standard urine drug screens generally detect morphine, hydrocodone, dihydrocodeine, codeine, 6-acetylmorphine (metabolite of heroin), and hydromorphone. They often don't detect fentanyl, buprenorphine, methadone, tramadol, oxycodone or some other synthetic and semi-synthetic opioids, requiring more specific or extensive testing to identify them.
Liver function tests, complete blood count, renal function.
Infectious disease screening → Hepatitis B/C, HIV, TB, STIs, and other blood-borne pathogens should be evaluated, especially in patients with injection drug use.
ECG: Consider ECG, especially if using methadone.
Combining opioids with sedative-hypnotics or alcohol significantly increases overdose risk and respiratory depression.
Rebound insomnia, anxiety, muscle aches/cramping often occur upon discontinuation, reinforcing dependence.
Symptoms:
Euphoria, drowsiness, sedation, respiratory depression (leading to hypoventilation), coma in severe cases.
Constipation, nausea, pinpoint pupils (miosis), confusion, and sometimes bradycardia.
Exclude other causes of altered mental status (e.g., head trauma, hypoxia, hypoglycemia, hypothermia, electrolyte abnormalities, encephalopathy, other intoxications).
Treatment:
Supportive care + airway protection. Ventilatory support may be required.
Naloxone: Rapidly reverses opioid effects; administered intravenously, intranasally, or intramuscularly. Additional doses every few minutes may be required if no response. Greater initial doses may be required in patients with apnea or respiratory arrest. Be prepared for recurrent symptoms and the need for repeat dosing due to naloxone’s shorter half-life compared to many opioids. May precipitate withdrawal symptoms in chronic users. Other risks include agitation, vomiting, cardiac arrhythmia, and pulmonary edema.
Monitoring: Continuous monitoring of vital signs, particularly respiratory rate and oxygen saturation. Patients should be monitored in an emergency or inpatient medical or ICU setting until stable. Consider restriction of visitors or search of body and belongings if risk of in-hospital overdose.
Be aware that some opioids have serotonergic properties (e.g., tramadol, meperidine, fentanyl, dextromethorphan, and methadone). Look for possible serotonin syndrome, particularly if taken in an overdose with antidepressants or other serotonergic medications.
Remember that withdrawal symptoms of a drug are usually opposite of its intoxication effects. For example, opioids are sedating and constipating, but withdrawal can → brain excitation, anxiety, insomnia, diarrhea, etc. Withdrawal from opioids is not life-threatening, but is very unpleasant.
With persistent opioid exposure, mu receptors become less responsive. Chronic opioid use inhibits norepinephrine release (in the locus coeruleus). In compensation, the brain increases the sensitivity and activity of noradrenergic neurons. Sudden removal of the opioid leads to a rapid drop in mu receptor activation. The previously suppressed locus coeruleus neurons become hyperactive. This results in a surge of norepinephrine, contributing to many of the withdrawal symptoms.
Symptoms:
Early symptoms: Anxiety, agitation, restlessness, muscle aches, insomnia, sweating, and runny nose.
Later symptoms: Abdominal cramping, diarrhea, dilated pupils, goosebumps, and nausea.
Autonomic dysregulation: Increased heart rate, high blood pressure, sweating, and lacrimation (tearing).
Time course: Varies depending on the specific opioid used; withdrawal from short-acting opioids occurs sooner but may be more intense, while long-acting opioids have a delayed onset.
Clinical Opiate Withdrawal Scale (COWS): The COWS scale can be used to monitor symptoms of withdrawal (similar to CIWA in alcohol withdrawal), which assesses resting heart rate, sweating, restlessness, pupil size, joint aches, runny nose or tearing, GI symptoms, tremor, yawning, anxiety or irritability, and gooseflesh skin.
Treatment:
Supportive treatment: Hydration, electrolyte replacement, and nutritional support.
Medication options for symptom reduction:
Autonomic symptoms (sweating, tachycardia, myoclonus): Clonidine is preferred. Alternatives include baclofen, gabapentin, and tizanidine.
Hydroxyzine can be used for anxiety, lacrimation, or rhinorrhea.
Muscle aches: NSAIDs or Tylenol
Insomnia: Trazodone or Hydroxyzine
Abdominal cramps: Dicyclomine
Diarrhea: Loperamide
Medication-Assisted Treatment (MAT) Initiation: Transitioning to a long-acting opioid agonist like methadone or a partial agonist like buprenorphine can be initiated after initial stabilization. MAT is more effective in treating withdrawal symptoms and retaining in treatment compared to clonidine. See next section for more details.
Warn patients that release from the hospital/rehab center is a risk factor for overdose death due to loss of tolerance.
•Effective treatment requires a combination of medical, psychological, and social interventions. A multi-disciplinary team—often including psychiatrists, primary care providers, therapists, social workers, and peer support specialists collaborates to address all aspects of the disorder.
Determine the Appropriate Treatment Setting: Choosing the right level of care depends on substance use severity, comorbid conditions, and prior treatment history. See Day 60: Intro to SUD for a description of each level of care.
Severe cases → inpatient detox, ideally followed by a residential treatment program, aka "rehab."
Mild/moderate cases → outpatient management with close follow-up. If outpatient treatment has failed, consider IOP or PHP.
Regardless of treatment setting, best practice may include random drug screening.
Monitoring for relapse and overdose risk is important in patients with polysubstance use histories.
Psychosocial Interventions:
Individual and/or group therapy should be part of every SUD treatment approach. See Day 60: Intro to SUD for a discussion of interventions that include behavioral therapies, peer support & 12-step programs, and family support resources.
Medication-Assisted Treatment (MAT):
Methadone: A full mu opioid agonist used in controlled settings to reduce cravings and withdrawal symptoms. Only available in federally licensed hospitals/clinics. There is a risk of QTc prolongation. Check an ECG before and during the first 24 hours of treatment.
Buprenorphine: A partial mu opioid agonist and kappa-antagonist that offers a ceiling effect for respiratory depression, making it safer in overdose scenarios. Available in combination with naloxone (Suboxone) to prevent IV misuse. In withdrawal management, wait for the COWS to decrease to 8-10 before starting due to the risk of precipitating withdrawal if started earlier. Due to recent data, generally favored over methadone in pregnancy due to better outcomes for newborns.
Naltrexone: A mu opioid antagonist used to prevent relapse; requires complete detoxification prior to initiation (7-10 days opioid-free). Less effective than methadone or buprenorphine for retention.
Emerging Therapies: Research is ongoing into additional interventions aimed at reducing abuse potential and enhancing recovery outcomes. Examples include Brixadi (buprenorphine extended-release injection), psychedelics (e.g., psilocybin and MDMA), and interventional modalities (e.g., transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)).
Avoidance of cross-tolerant substances like alcohol and other CNS depressants is crucial for recovery.
Conclusion
•I hope you found this lesson helpful. Opioid use disorder is a major public health crisis and effective management utilizes a combination of psychosocial supports, thorough medical assessments, and pharmacological interventions.
•In our next post we will discuss stimulant abuse, focusing on methamphetamine, amphetamines, and cocaine.
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