Methadone is the Most Common Prescription Opioid Involved in Overdose Deaths
Methadone is the most common prescription opioid involved in overdose deaths relative to its prescribing frequency, accounting for as much as one-third of opioid-related overdose deaths despite representing less than 2% of opioid prescriptions outside of opioid treatment programs. 1
Comparative Overdose Risk Among Prescription Opioids
Methadone
- Disproportionately high overdose risk due to its complex pharmacokinetics
- Accounts for up to one-third of opioid-related overdose deaths despite representing <2% of opioid prescriptions 1
- Associated with cardiac arrhythmias and QT prolongation that increase mortality risk
- Of 191 methadone-related deaths in one study, only two were patients in opioid treatment programs, indicating most deaths occur from prescribed methadone for pain 2
Oxycodone (OxyContin)
- Immediate-release oxycodone was involved in a high number of opioid-related deaths 2
- Shows a strong increasing linear trend between dose strength and proportion of prescriptions dispensed to decedents 2
- In one study, 61% of oxycodone overdose decedents had filled a prescription for oxycodone in the 60 days prior to death 2
Hydromorphone (Dilaudid)
- While hydromorphone contributes to overdose deaths, it is not identified in the evidence as being among the most common causes of prescription opioid overdose deaths
- Less frequently implicated compared to methadone and oxycodone based on the provided evidence
Oxymorphone
- Limited specific data in the provided evidence regarding oxymorphone's contribution to overdose deaths
- Not identified as one of the most common prescription opioids involved in overdose deaths in the available evidence
Risk Factors for Prescription Opioid Overdose
Dose-Dependent Risk
- Higher opioid dosages are strongly associated with increased overdose risk 3
- Compared with dosages <20 MME/day, the odds of overdose increase significantly:
- 1.3-1.9 times higher for 20 to <50 MME/day
- 1.9-4.6 times higher for 50 to <100 MME/day
- 2.0-8.9 times higher for ≥100 MME/day 3
Formulation Considerations
- Extended-release/long-acting opioids have higher overdose risk than immediate-release formulations, particularly at therapy initiation 1
- However, immediate-release oxycodone was involved in more deaths than extended-release formulations in some studies 2
Polypharmacy
- Concurrent use of benzodiazepines and opioids significantly increases overdose risk
- Evidence of concurrent benzodiazepine use was found in 31%-61% of opioid overdose decedents 3, 1
- Multiple drug involvement is common - in one study, 96.7% of opioid-related deaths involved at least one other contributory drug 4
Clinical Implications
Prescribing Considerations
- Methadone should be avoided for pain management when alternatives exist due to its disproportionate overdose risk 1
- Careful dose titration is essential for all opioids, with particular caution at doses above 50 MME/day
- Prescription Drug Monitoring Programs (PDMPs) should be utilized to identify potential doctor shopping and reduce overdose risk 3, 1
High-Risk Populations
- Patients with sleep apnea or other causes of sleep-disordered breathing
- Those with renal or hepatic insufficiency
- Older adults
- Patients with depression or other mental health conditions
- Patients with alcohol or other substance use disorders 3
Prevention Strategies
- Consider naloxone prescriptions for high-risk patients
- Implement opioid treatment contracts
- Provide patient education about overdose risks
- Avoid co-prescribing benzodiazepines with opioids 1
In conclusion, while all prescription opioids carry overdose risk, methadone stands out as having a disproportionately high association with overdose deaths relative to its prescribing frequency. This makes it the most common prescription opioid involved in overdose deaths among the options presented.