Can alprazolam (Xanax), zolpidem (Ambien), and muscle relaxers be taken together?

From the Guidelines

No, alprazolam (Xanax), zolpidem (Ambien), and muscle relaxers should not be taken together due to the increased risk of central nervous system depression and respiratory depression, which can be potentially fatal 1.

Key Considerations

• Benzodiazepines, such as alprazolam, and opioids can cause central nervous system depression and decrease respiratory drive, increasing the risk of overdose and death 1.
• Zolpidem, a non-benzodiazepine hypnotic, can also potentiate central nervous system depression when taken with other central nervous system depressants, such as muscle relaxants 1.
• Muscle relaxants, such as cyclobenzaprine and metaxalone, can contribute to the risk of central nervous system depression and falls in older adults 1.

Recommendations

• Clinicians should avoid prescribing multiple central nervous system depressants concurrently whenever possible 1.
• If concurrent use is necessary, clinicians should carefully weigh the benefits and risks, monitor patients closely, and consider involving pharmacists and pain specialists in the management team 1.
• Patients taking benzodiazepines, such as alprazolam, and other central nervous system depressants, such as zolpidem and muscle relaxants, should be closely monitored for signs of central nervous system depression and respiratory depression 1.

From the FDA Drug Label

Coadministration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression [see DRUG INTERACTIONS (7. 1)]. Dosage adjustments of zolpidem tartrate and of other concomitant CNS depressants may be necessary when zolpidem tartrate is administered with such agents because of the potentially additive effects.

The combination of alprazolam (Xanax), a benzodiazepine, zolpidem (Ambien), and muscle relaxers may increase the risk of CNS depression.

• Key considerations:
  • Increased risk of CNS depression with concomitant use of CNS depressants
  • Potential for additive effects with other CNS depressants
  • Need for dosage adjustments when administering zolpidem with other CNS depressants Given the potential for increased risk of CNS depression, it is recommended to exercise caution when considering concomitant use of these medications. 2 2

From the Research

Interaction between Alprazolam, Zolpidem, and Muscle Relaxers

• The combination of opioids with benzodiazepines and skeletal muscle relaxants has been reported to potentiate the 'high' and induce a synergistic increase in dopamine in the nucleus accumbens (NAc) and depression of respiration 3.
• However, there is no direct evidence on the interaction between alprazolam (Xanax), zolpidem (Ambien), and muscle relaxers.
• Studies have shown that benzodiazepines, including alprazolam, can cause respiratory depression, and the addition of skeletal muscle relaxants can further enhance this effect 3.
• Zolpidem, a non-benzodiazepine sedative-hypnotic, has been shown to cause sedation and myorelaxation, and its combination with ethanol can lead to reduced motor performance and grip strength 4.
• Muscle relaxants, including benzodiazepines and non-benzodiazepines, have been shown to have adverse effects, such as dizziness and drowsiness, and their use is not recommended for patients with rheumatoid arthritis due to the lack of evidence supporting their efficacy 5.

Safety and Efficacy of Combination Therapy

• The safety and efficacy of combination therapy with alprazolam, zolpidem, and muscle relaxers have not been established.
• Deprescribing zolpidem has been shown to reduce the risk of falls and fractures in patients with cirrhosis, but the effect of deprescribing benzodiazepines on liver health is unknown 6.
• The vasorelaxant effects of benzodiazepines, non-benzodiazepine sedative-hypnotics, and tandospirone have been demonstrated, which may contribute to their adverse effects, such as decreased blood pressure and depressed baroreflex function 7.

Potential Risks and Consequences

• The combination of alprazolam, zolpidem, and muscle relaxers may increase the risk of respiratory depression, sedation, and myorelaxation.
• The use of these medications together may also increase the risk of falls, fractures, and other adverse effects, particularly in vulnerable populations, such as the elderly or those with cirrhosis.
• Therefore, caution is advised when considering combination therapy with these medications, and patients should be closely monitored for potential adverse effects.