Combination therapy with methadone and duloxetine for cancer-related pain: a retrospective study

Background: A comprehensive approach to pain management often requires multimodal therapy and a combination of medications. Oncology patients may be prescribed methadone and duloxetine as single agents or in combination for cancer-related pain, particularly neuropathic pain. Duloxetine is also prescribed for depression or anxiety in patients with cancer. Methods: A retrospective chart review on patients with cancer-related pain prescribed duloxetine and methadone combination therapy at the Virginia Commonwealth University supportive care clinic (SCC) between 2012 and 2019. Edmonton Symptom Assessment System (ESAS) scores reported by patients on monotherapy were compared to scores after they started combination therapy. Of 131 patients identified on combination therapy, 43 met study criteria (2 with incomplete ESAS scores). Results: ESAS total and subscores after combination therapy were lower than on monotherapy. Combination therapy decreased total, pain, and emotion subscores by 5.6 (SD =17.3, d(z)=-0.32, P=0.046), 0.9 (SD =3.0, d(z)=-0.30, P=0.052), and 1.8 (SD =5.1, d(z)=-0.36, P=0.023), respectively. On combination therapy, 28% of patients reported at least a two-point reduction in pain scores. All study participants reported cancer pain with neuropathic components; most had mixed pain syndromes comprising nociceptive and neuropathic components. Adherence rates were high as 81% of patients with follow-up appointments continued therapy. Conclusions: These results suggest the combination of duloxetine and methadone reduces cancer-related pain and emotional symptom burden compared to either medication as a single agent.