Is it illegal to prescribe opiates (opioid analgesics) and benzodiazepines in combination?

Prescribing Opioids and Benzodiazepines in Combination

It is not illegal to prescribe opioids and benzodiazepines in combination, but it is strongly discouraged due to significant mortality risks, and clinicians should avoid this practice whenever possible due to the 3-10 fold increased risk of fatal overdose. 1, 2

Risks of Co-Prescribing

• Mortality Risk: Concurrent use of benzodiazepines and opioids creates dangerous synergistic effects on respiratory depression, with studies showing:

  • 3-10 fold higher death rates compared to opioids alone 1
  • Evidence of concurrent benzodiazepine use in 31-61% of opioid-related fatal overdoses 1
  • Near quadrupling of overdose death risk compared to opioid prescription alone 2

• Physiological Effects: Both medication classes cause central nervous system depression, with their combined effect substantially potentiating respiratory depression 2

• Lack of Therapeutic Benefit: For many common painful conditions, there is no demonstrated superiority when combining these medications compared to safer therapeutic alternatives 1

Regulatory Guidance and Warnings

• The FDA added a black box warning in 2016 to both opioids and benzodiazepines specifically recommending against co-prescribing 1

• The CDC Guideline for Prescribing Opioids (2016) explicitly states: "Clinicians should avoid prescribing opioids and benzodiazepines concurrently whenever possible" 1

• Multiple quality and safety organizations have developed guidelines against this practice, including the National Quality Forum and the Department of Veterans Affairs 1

When Co-Prescribing Is Considered

If a clinician determines co-prescribing is absolutely necessary (which should be rare):

1. Document clear medical necessity for concurrent therapy 2

2. Check PDMP data before every prescription to identify:

   • High total opioid dosages
   • Dangerous combinations
   • Multiple prescribers 1

3. Implement risk mitigation strategies:

   • Prescribe naloxone to patients and educate household members on its use 1, 2
   • Use the lowest effective doses of both medications 2
   • Increase monitoring frequency with more office visits 2
   • Conduct regular urine drug testing 1

4. Have explicit discussions with patients about:

   • Increased overdose risks
   • Safety concerns
   • Alternative treatment options 1

Alternative Management Approaches

• Consider evidence-based psychotherapies (e.g., CBT) for anxiety instead of benzodiazepines 2

• Use non-benzodiazepine medications approved for anxiety 2

• Prioritize non-opioid pain management strategies when possible 2

• If tapering is needed, it's generally safer to taper opioids first due to greater risks of benzodiazepine withdrawal 2

Common Pitfalls to Avoid

• Never abruptly discontinue either medication in patients already taking both, as this could lead to dangerous withdrawal 2

• Don't dismiss patients from care based solely on urine drug test results showing concurrent use, as this could constitute patient abandonment 1, 2

• Don't ignore PDMP data showing multiple prescribers of controlled substances 1

• Avoid prescribing additional CNS depressants (muscle relaxants, hypnotics) that can further potentiate respiratory depression 2

While not illegal, the combination of opioids and benzodiazepines presents such significant risks that clinicians should consider it a practice to avoid in nearly all circumstances, with careful risk mitigation strategies implemented in the rare cases where benefits might outweigh risks.