Alprazolam × Morphine

Alprazolam and morphine depress the central nervous system and respiratory centre through different routes (GABA-A and μ-opioid). Effects are additive – risk of fatal respiratory depression rises several-fold. FDA boxed warning applies to all opioid + benzodiazepine combinations since 2016.

Drowsiness, slowed and shallow breathing (respiratory rate below 12/min), cyanosis of lips and nail beds. Severe cases progress to respiratory arrest and death. Symptoms are easy to miss, so the patient and family are warned in advance.

Avoid the combination. For anxiety on opioid therapy, use non-benzodiazepine anxiolytics: gabapentinoids, hydroxyzine, or SSRIs for long-term control. For panic disorder with palliative cancer pain, minimal doses of both under respiratory monitoring with naloxone available.