Drug interactions in chronic pain disorder, addiction and affective disorder. Clinic, treatment and TDM

Drug therapy in patients with chronic pain and psychiatric comorbidities can be challenging cause of relevant drug interactions which should be taken into account in clinical practice. Here we present two cases of chronic pain and depression. Patient 1 additionally suffered from opioid- and tobacco addiction and was treated with oxycodone, duloxetine and mirtazapine by underlying opioid- and tobacco addiction. Patient 2 met the criteria for opioid- and tobacco addiction, and was treated with tramadol, doxepin or duloxetine. Tramadol is a prodrug and converted by CYP2D6 into a pharmacologically active drug. Duloxetine is metabolized by CYP1A2 and CYP2D6 (inhibition). Mirtazapine is metabolized by CYP1A2, doxepin CYP 2D6, 2C19, oxycodone by CYP 2D6, CYP3A4.

As methods, clinical course documentation and measurement of drug levels were applied.

Results: 1. Patient with oxycodone- and tobacco addiction and depression: Neither under duloxetine, nor even with mirtazapine plasma levels could be achieved in a therapeutic range. 2. Patient with tramadol- and tobacco addiction and depression: tramadol-intoxication (in serum 1700 µg/l, therapeutic range 100 – 800 µg/l, toxic > 1000 µg/l, lethal > 2000 µg/l, desmethyltramadol µg/l, therapeutic range 5 – 123 µg/l). Due to the withdrawal of tramadol a combination of doxepin or duloxetine was chosen, which affected a sufficient plasma level. Pat. left the clinic prematurely, probably there was not sufficient desmethyltramadol available.

The treatment of depressive symptoms comorbid to opioid addiction and chronic pain syndrome with antidepressants indicates the necessity of individualized treatment, taking account of TDM.