Opioid Combination Therapy for Chronic Pain

Introduction to Opioid Therapy

The Centers for Disease Control and Prevention recommends calculating a patient's total morphine milligram equivalent (MME) dose, with hydrocodone having a conversion factor of 1.0 MME and tramadol converting at 0.2 MME 1
The American College of Physicians and other guideline societies support the idea that adding tramadol to hydrocodone simply increases total opioid burden without evidence of superior analgesia compared to optimizing a single agent 2, 3

Direct comparative trials found no significant difference in analgesic efficacy between tramadol and hydrocodone when used individually, with tramadol producing a higher percentage of side effects 2, 3
The World Health Organization's "weak opioid" step has questionable efficacy beyond 30-40 days, with most patients requiring escalation due to insufficient analgesia rather than side effects 2, 3

The CDC guidelines recommend pausing and reassessing before increasing total opioid dosage to ≥50 MME/day, as many patients do not experience benefit in pain or function from increasing beyond this threshold 1
Consider adding non-opioid analgesics or adjuvant medications for neuropathic pain components, providing multimodal analgesia without compounding opioid-related risks 2, 3

If combining opioids, calculate the combined MME and be aware that exceeding the 50 MME threshold requires careful reassessment of benefits versus risks 1
Tramadol has additional serotonergic activity and is contraindicated with MAO inhibitors, requiring extreme caution with SSRIs, SNRIs, or tricyclic antidepressants due to serotonin syndrome risk 4