Arai, Y.C., Matsubara, T., Shimo, K., Suetomi, K., Nishihara, M., Ushida, T., . . . Arakawa, M. (2010). Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine. Journal of Anesthesia, 24, 407–410.

To determine if low-dose gabapentin, combined with low-dose imipramine, is effective in treating cancer-related neuropathic pain

Patients were randomly assigned to one of four groups. Patients in group 1 received gabapentin 200 mg and imipramine 10 mg every 12 hours. Patients in group 2 received gabapentin 200 mg every 12 hours. Patients in group 3 received gabapentin 400 mg every 12 hours. Patients in group 4 received imipramine 10 mg every 12 hours. Pain assessment occurred at baseline and at seven days after the start of medication. Opioid rescue medication was available as needed. Nonsteroidal anti-inflammatory drugs (NSAIDs) were continued if used. No other pain medication changes were made.

• The study reported on 52 patients.
• Age range across all groups was 58–79 years.
• The sample was 52% female and 48% male.
• Patients had a variety of cancer types, including breast, lung, neck, prostate, pancreatic, gynecologic, and gastrointestinal cancers, as well as sarcoma.
• All patients had neuropathic pain. At baseline, daily opioid dose was 22.5–120 mg/day; patients were receiving either sustained-release oxycodone or fentanyl patch for pain management. All patients had inadequately controlled neuropathic pain.

• Single site
• Outpatient setting
• Japan

The study was a randomized, prospective, parallel-group trial.

Numeric rating scale (NRS), 0–10, to measure pain

Compared to baseline scores, scores relating to low-dose gabapentin-imipramine showed that the combination significantly decreased pain and daily pain episodes (p < 0.05). Compared to the other treatments, gabapentin-imipramine was the most effective (p < 0.001). The drug combination was associated with decreased doses of rescue opioids. Only the scores of the group treated with low-dose gabapentin-imipramine showed a significant reduction in pain.

The combination of low-dose gabapentin and imipramine was effective in reducing neuropathic pain.

• The study had a small sample, with fewer than 100 patients.
• Authors provided no information about analysis of differences in the use of rescue medication.
• The follow-up period was only seven days.

The use of a combination of low-dose gabapentin and imipramine, as adjuvant analgesia, can improve pain control in patients with neuropathic pain. This study demonstrates that neither of these drugs alone, in different dosages, effected the improvement. Note that this study does not establish long-term efficacy or side effects.