Amitriptyline × Morphine

Amitriptyline increases the sedative effect of other central nervous system depressants (amitriptyline SmPC), and morphine combined with such drugs can cause respiratory depression, low blood pressure, deep sedation and coma (morphine SmPC). The second mechanism is the anticholinergic effect of amitriptyline: with morphine it raises the risk of severe constipation, paralytic ileus and urinary retention (morphine SmPC). The third is serotonergic: the US Food and Drug Administration (FDA) warns about serotonin syndrome when opioids are combined with tricyclic antidepressants (morphine FDA label).

Deep sedation, drowsiness, confusion, slow or shallow breathing, low blood pressure. Severe constipation, bloating and abdominal pain, urinary retention. In older people: confusion, delirium, falls. With serotonin syndrome: changes in mental state, swings in blood pressure and pulse, sweating, fever, tremor and muscle twitching, nausea and diarrhoea.

The morphine SmPCs require reduced doses and the greatest caution in patients who take tricyclic antidepressants (morphine SmPCs). The oral morphine SmPC lists antidepressants among central nervous system depressants and requires limiting the dose and duration of concomitant use (oral morphine SmPC). Morphine is not recommended with drugs that have anticholinergic action unless strictly necessary; if they are combined, reduce the dose of the other drug and monitor the patient closely (injectable morphine SmPC). Watch the patient for respiratory depression and excessive sedation, urinary retention and slowed bowel movement (morphine SmPCs). The US Food and Drug Administration (FDA) asks for frequent evaluation of the patient, especially at the start of treatment and after dose changes, and for stopping morphine if serotonin syndrome is suspected (morphine FDA label).