Keskinbora, K., Pekel, A.F., & Aydinli, I. (2007). Gabapentin and an opioid combination versus opioid alone for the management of neuropathic cancer pain: A randomized open trial. Journal of Pain and Symptom Management, 34, 183–189.

To compare a gabapentin-opioid combination to opioid monotherapy, in terms of safety and efficacy, in the management of neuropathic pain

Patients were randomized to one of two groups. One group received treatment with gabapentin added to ongoing opioids. Gabapentin was gabapentin titrated to pain; in this group (group GO), opioids were kept constant. In the other group (group OO), opioid monotherapy was continued according to the World Health Organization (WHO) ladder approach. The initial gabapentin dose was 100 mg three times daily for patients older than age 60 and 300 mg TID for those younger than age 60. Treatment was titrated to these doses in three days and to 3,600 mg per day according to response. GO patients could take gabapentin as a rescue drug.

• The sample was comprised of 75 patients who were receiving opioids with minimal opioid side effects and had unrelieved neuropathic pain; 63 patients completed the trial.
• All patients had a Karnofsky Performance Status score greater than 60 and a pain intensity score of 4 or higher.
• Patients were excluded from the study if they were taking adjuvant drugs and nonopioid analgesics.
• Patients were removed from the study if new pain from disease progression occurred or if intolerable side effects developed.

• Single site
• Turkey

The study was a randomized, single-site, open trial.

• Numeric rating scale (NRS) to measure pain intensity, specifically burning and shooting
• Mean absolute change in pain intensity at day 13
• Allodynia (Allodynia was assessed by stroking painful and nonpainful areas with a light cotton material. If normal response was noted in nonpainful area but pain or unpleasant sensation was noted in painful area, allodynia was said to be present.)
• Analgesic drug consumption, including rescue, evaluated on day 4 and day 13
• Side effects

• Both treatments resulted in significant reduction in pain intensity on day 4 and day 13, compared to baseline.
• Mean pain intensity for burning or shooting pain was significantly higher in group OO than in group GO at both assessment times (p = 0.0001). However, there was a clinically meaningful reduction in group OO.
• Data showed a significant decrease in allodynia (p = 0.002) in group GO at day 4.
• The rate of side effects was significantly lower (p = 0.015) in group GO.
• One patient in the group GO withdrew from the study because of respiratory depression. The patient was taking gabapentin and sustained-release morphine and was age 66. Depression occurred three days after the addition of gabapentin. Respiratory depression should be considered when using gabapentin and morphine, particularly in older adults.
• In terms of the most frequent causes of pain, 32.3% of GO patients had malignant sacral plexopathy, and 28.15% of OO patients had brachial plexopathy.
• GO patients remained at the same step of the ladder at day 4. Group OO patients, who took a weak opioid at the second step, all progressed to the third step. This may explain why fewer patients in group GO experienced side effects.

This study suggests that gabapentin added to opioids provides better relief than opioid monotherapy. Gabapentin-opioid treatment may be a first-line treatment for the specified patients.

• The means of measuring allodynia are questionable.
• The primary neuropathic syndromes were different in each group.
• The WHO ladder has been abandoned by many practitioners, who now follow National Comprehensive Cancer Network or American Pain Society guidelines.