Major
Established
Description
Alprazolam combined with morphine carries an FDA boxed warning for serious risk of respiratory depression, sedation, coma, and death.
Mechanism
Alprazolam potentiates GABA-A inhibitory tone; morphine reduces brainstem respiratory drive via mu-opioid receptors — both pathways converge on CNS and respiratory depression.
Clinical Significance
Large database studies confirm excess mortality with concomitant benzodiazepine and opioid prescriptions.
Management
Prescribe concurrent opioids and benzodiazepines only when alternatives are inadequate; coprescribe naloxone.