What are the primary causes of opioid overdose in Hawaii, which populations are most affected, and what interventions can reduce overdose mortality?

Primary Causes of Opioid Overdose in Hawaii

The primary causes of opioid overdose are high-dose prescribing (>80-100 MME/day), concurrent use of benzodiazepines or alcohol, and increasingly, contamination of the illicit drug supply with synthetic opioids like fentanyl. 1

Medication-Related Causes

High-Dose Opioid Prescribing

• Opioid doses exceeding 80-100 morphine milligram equivalents (MME) per day are disproportionately associated with overdose-related emergency department admissions and deaths 1
• Compared to doses <20 MME/day, the odds of overdose increase 1.9-4.6 fold at 50-100 MME/day and 2.0-8.9 fold at ≥100 MME/day 1
• Long-acting opioids, particularly methadone and extended-release oxycodone, carry higher overdose risk than short-acting formulations 1
• Methadone accounts for approximately one-third of opioid-related overdose deaths despite representing <2% of opioid prescriptions 1

Dangerous Drug Combinations

• The CDC explicitly identifies benzodiazepines as dangerous combinations with opioids that put patients at high risk for overdose, with the FDA drug label for diazepam carrying a black box warning stating that concomitant use may result in profound sedation, respiratory depression, coma, and death 2
• Concurrent benzodiazepine use is found in 31-61% of fatal opioid overdose cases 1
• Alcohol increases risks for respiratory depression, profound sedation, and death when combined with opioids 1, 2

Synthetic Opioid Contamination

• From 2013 to 2019, the synthetic opioid-involved death rate increased 1,040%, from 1.0 to 11.4 per 100,000 age-adjusted 3
• Between 2013 and 2014, deaths involving synthetic opioids other than methadone (primarily illicitly manufactured fentanyl) increased 80% 4
• The sharp increase in synthetic opioid deaths coincided with law enforcement reports of increased availability of illicitly manufactured fentanyl 4

Patient-Specific Risk Factors

Prior Overdose and Substance Use History

• A history of prior overdose substantially increases future overdose risk 1, 5
• A history of substance use disorder, particularly alcohol, benzodiazepines, or opioids, is a major risk factor for overdose 1, 5
• Patients with mental health comorbidities and histories of substance use disorders are at higher risk for opioid use disorder 1

Medical Comorbidities

• Health problems associated with respiratory compromise increase overdose risk 1
• Central sleep apnea is a specific risk factor for opioid overdose 1
• Renal or hepatic dysfunction increases overdose risks because clearance of many opioid drugs is impaired, leaving higher and longer-lasting drug levels in the blood 1

Mental Health Factors

• Prior suicidal thoughts/attempts or a diagnosis of major depression are markers for elevated risk of overdose, as some proportion of overdoses may be purposeful suicide attempts 1
• Depressed patients are at higher risk for drug overdose than patients without depression, particularly at higher opioid dosages 1

Populations Most Affected

Age Groups

• For individuals aged 24-35 years, opioids caused 20% of deaths, with drug-induced death being the leading cause of death in this age group 1
• Persons aged 25-44 years and ≥55 years experienced significant increases in overdose death rates 4

Demographic Patterns

• Non-Hispanic whites and non-Hispanic blacks experienced significant increases in overdose death rates 4
• The typical prescription opioid abuser was white, male, and 45-55 years of age 6

Youth Populations

• Over 4,000 adolescents and young adults died from opioids in 2016, totaling 230,694 years of premature life lost 1
• Death rates involving synthetic opioids among adolescents increased from 0.1 in 2002 to 0.7 in 2015 1
• National data suggest that opioid misuse in youth is often precipitated by exposure to opioids for acute pain management or through diversion 1

Interventions to Reduce Overdose Mortality

Naloxone Distribution

• Expanding access to naloxone has been shown to significantly reduce opioid overdose fatalities 1
• Naloxone distribution through community-based programs providing prevention services has been demonstrated to be associated with decreased risk for opioid overdose death at the community level 1
• However, naloxone only reverses opioid effects at μ-opioid receptors and has no effect on benzodiazepines, alcohol, or xylazine 2

Risk Assessment and Monitoring

• Review prescription drug monitoring program (PDMP) data before every opioid prescription to identify dangerous combinations 2
• Perform urine drug testing before starting opioid therapy and at least annually during chronic opioid therapy to ensure no presence of other drugs that may magnify opioid effects on respiration 1, 2
• Conduct thorough risk assessment including validated screening with Drug Abuse Screening Test (DAST) and Alcohol Use Disorders Identification Test (AUDIT) 2, 5

Prescribing Modifications

• Avoid doses greater than 90-200 mg of morphine equivalents per day 1
• If patients are receiving opioids plus benzodiazepines, discuss safety concerns including increased risk for respiratory depression and overdose, and avoid prescribing opioids and benzodiazepines concurrently whenever possible 2
• Exercise greater caution in prescribing high opioid doses or long-acting opioids when risk factors are present 1

Patient Education and Follow-up

• Provide much greater patient and family education about overdose risks when risk factors are identified 1
• The CDC recommends explicit counseling about the absolute necessity to avoid alcohol during opioid therapy 2
• Implement frequent clinical follow-up, re-evaluating more frequently than every 3 months for high-risk patients 2, 5

Treatment for Opioid Use Disorder

• Methadone and buprenorphine for opioid use disorder have been found to increase retention in treatment and decrease illicit opioid use 1
• Effectiveness is enhanced when psychosocial treatments (contingency management, community reinforcement, psychotherapeutic counseling, and family therapy) are used in conjunction with medication-assisted therapy 1

Critical Pitfalls to Avoid

• Never dismiss patients from practice based on PDMP findings showing dangerous combinations—this creates missed opportunities for potentially lifesaving interventions 2
• Do not assume naloxone will reverse all effects of polysubstance overdoses—naloxone only reverses opioid effects and has no effect on benzodiazepines, alcohol, or xylazine 2
• Avoid equating tolerance and physical dependence with addiction—these are common and expected consequences of repeated opioid exposure, while addiction occurs far more rarely and develops much more slowly 1