Moderate
Amitriptyline × Morphine
Tricyclic antidepressants (TCA)×Natural opium alkaloids
Mechanism
Additive CNS depression, sedation, and anticholinergic effect (constipation, urinary retention). Older patients: delirium and fall risk.
Symptoms
Deep sedation, drowsiness, confusion. Constipation and urinary retention (amitriptyline anticholinergic effect amplified by opioid constipation). Older patients: delirium risk.
Management
The combination is common in cancer pain with depression or neuropathic pain. In older patients and palliative care: constipation prophylaxis (lactulose, polyethylene glycol) and urine output monitoring. Alternative antidepressant without anticholinergic effect: mirtazapine or agomelatine.