Is it safe to prescribe a narcotic (opioid) with a benzodiazepine?

Concurrent Prescribing of Opioids and Benzodiazepines: Safety and Regulatory Considerations

Clinicians should avoid prescribing opioids and benzodiazepines concurrently whenever possible due to the significantly increased risk of fatal respiratory depression, with concurrent use associated with a near quadrupling of overdose death risk compared to opioid prescription alone. 1

Risks of Concurrent Prescribing

The combination of opioids and benzodiazepines creates a dangerous synergistic effect:

• Both medications cause central nervous system depression and decrease respiratory drive 1
• Epidemiologic studies show concurrent benzodiazepine use in a large proportion of opioid-related overdose deaths 1
• Recent research shows patients with opioid overdose and concomitant benzodiazepine exposure have higher rates of mechanical ventilation and poorer response to naloxone 2
• The mortality risk increases by 75-90% when benzodiazepines are prescribed alongside opioid agonist treatment 3

DEA and Regulatory Considerations

The FDA added black box warnings to both opioids and benzodiazepines in 2016 specifically recommending against co-prescribing these agents 1. While there are no absolute prohibitions against co-prescribing from the DEA, prescribers should:

• Document clear medical necessity for concurrent therapy
• Check state Prescription Drug Monitoring Program (PDMP) data before prescribing and periodically during therapy 1
• Review for dangerous combinations or high total opioid dosages from multiple prescribers 1
• Consider involving pharmacists and pain specialists as part of the management team when co-prescribing is deemed necessary 1

Limited Exceptions to Consider

There are rare circumstances when co-prescribing might be appropriate:

• Severe acute pain in a patient taking long-term, stable low-dose benzodiazepine therapy 1
• When benefits clearly outweigh risks and no suitable alternatives exist

In these cases:

• Use the lowest effective doses of both medications
• Increase monitoring frequency
• Consider offering naloxone to patients and their households 1
• Implement additional risk mitigation strategies

Risk Mitigation Strategies When Co-Prescribing Is Unavoidable

If co-prescribing cannot be avoided:

1. Prescribe naloxone to patients at increased risk for overdose, including those:

   • With history of overdose or substance use disorder
   • Taking benzodiazepines with opioids
   • Taking higher opioid dosages (≥50 MME/day) 1

2. Increase monitoring frequency:

   • More frequent office visits
   • Regular urine drug testing
   • PDMP checks with every prescription 1

3. Patient education:

   • Discuss increased overdose risk
   • Provide overdose prevention education
   • Train patients and household members on naloxone use 1

When Tapering Is Needed

When patients are already on both medications and tapering is required:

• It is generally safer to taper opioids first due to greater risks of benzodiazepine withdrawal 1
• Benzodiazepines should be tapered gradually if discontinued (typically 25% reduction every 1-2 weeks) 1, 4
• Abrupt benzodiazepine withdrawal can cause rebound anxiety, hallucinations, seizures, and rarely death 1
• Consider cognitive behavioral therapy to increase tapering success rates 1, 4

Alternative Approaches

For patients with anxiety who need pain management:

• Consider evidence-based psychotherapies (e.g., CBT) for anxiety 1, 4
• Use specific antidepressants or other non-benzodiazepine medications approved for anxiety 1, 4
• Prioritize non-opioid pain management strategies when possible 1

Common Pitfalls to Avoid

1. Never abruptly discontinue either medication in patients already taking both
2. Don't dismiss patients from care based on urine drug test results showing concurrent use, as this could constitute patient abandonment 1
3. Don't ignore PDMP data showing multiple prescribers of controlled substances 1
4. Avoid prescribing other CNS depressants (muscle relaxants, hypnotics) that can further potentiate respiratory depression 1

By following these guidelines, clinicians can minimize risk to patients while ensuring appropriate pain and anxiety management, and reduce their regulatory risk with the DEA.