Codeine and hydromorphone need to be converted to an active form in the liver. Anidepressants use the cytochrome CYP2D6 system in the liver and may cut down conversion and hence opioid effectiveness. This has been determined in post-operative pains in people on SSRI anti-depressants. However common antidepressants used in chronic pain – amitriptyline, venlafaxine and duloxetine – all use the CYP2D6 system as well.
Parthipan, Arjun, et al.
Predicting inadequate postoperative pain management in depressed patients: A machine learning approach.
PloS one 14.2 (2019): e0210575.
The list of drugs they tested included:
at 3 weeks, those on an SSRI and a prodrug had pain levels 1.1/10 higher.
Comment – obviously dosage was not adjusted to pain response so those on prodrug with an SSRI had more pain.