Can benzodiazepines be prescribed with kratom?

Benzodiazepines Should Not Be Prescribed with Kratom Due to Significant Risk of Fatal Respiratory Depression

Benzodiazepines should not be prescribed concurrently with kratom due to the high risk of respiratory depression, sedation, and potentially fatal overdose. 1 Both substances act as central nervous system depressants, and their combination significantly increases the risk of adverse outcomes.

Mechanism of Concern

• Kratom contains alkaloids (primarily mitragynine and 7-hydroxymitragynine) that act on opioid receptors 2, 3
• Benzodiazepines and opioid-like substances both cause central nervous system depression and can decrease respiratory drive 4
• The CDC and other guidelines explicitly warn against combining benzodiazepines with opioids, as this combination increases overdose death risk nearly four-fold compared to opioid use alone 4, 1

Evidence Against Co-Prescription

1. FDA and Regulatory Guidance:

   • The FDA added a black box warning in 2016 to both opioids and benzodiazepines recommending against co-prescribing these agents 4
   • Multiple clinical guidelines recommend avoiding concurrent use of multiple central nervous system depressants 1

2. Pharmacological Interactions:

   • Kratom exhibits inhibition at multiple cytochrome P450 isozymes (3A4, 2C9, 2D6, 1A2) involved in metabolism of prescription medications 5
   • This inhibition can increase systemic exposure of benzodiazepines, potentially leading to toxicity 5

3. Documented Risks:

   • Kratom has been associated with severe adverse effects including respiratory depression, seizures, and death 2, 3
   • These risks are significantly compounded by polysubstance use 3
   • Case reports document serious adverse events when kratom is combined with other serotonergic or CNS depressant medications 5

Clinical Considerations

Despite kratom having a lower risk of respiratory depression compared to traditional opioids when used alone 6, the combination with benzodiazepines introduces significant danger:

• Kratom is increasingly used as a self-treatment for opioid withdrawal, pain management, and mental health conditions 7
• Many patients may not disclose kratom use as it's an unregulated supplement
• Healthcare providers should specifically ask about kratom use when prescribing benzodiazepines

Alternative Approaches

For patients using kratom:

• Consider non-benzodiazepine alternatives for anxiety (SSRIs, SNRIs, buspirone)
• For sleep issues, consider non-benzodiazepine sleep aids or behavioral interventions
• For patients with substance use disorders, consider evidence-based treatment options including medication-assisted treatment 4, 1

Important Monitoring if Co-Use Cannot Be Avoided

If a patient is using both substances despite recommendations:

• Educate about risks of respiratory depression and overdose
• Consider prescribing naloxone and providing overdose education
• Monitor closely for signs of sedation, respiratory depression
• Use the lowest possible effective doses of both substances
• Implement a clear tapering plan to discontinue one or both substances

Conclusion

The combination of benzodiazepines with kratom presents similar dangers to the well-documented risks of combining benzodiazepines with traditional opioids. Given the significant risk of respiratory depression, sedation, and fatal overdose, concurrent use should be avoided whenever possible.