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. 

The objective of this study was to compare the safety and efficacy of gabapentin with opioid versus opioid monotherapy for the management of neuropathic pain.

Patients were randomized to one of two groups: Group GO included gabapentin added to ongoing opioids, gabapentin titrated to pain, and opioids kept constant; group OO saw the continuation of opioid monotherapy using the World Health Organization ladder approach.

Regarding dosing, gabapentin was initially given at 100 mg three times daily for patients aged 60 and older and 300 mg three times daily for those younger than age 60. Doses were titrated over the three days—up to 3,600 mg per day according to response. Patients in the GO group also could take gabapentin as a rescue drug.

• Seventy-five patients who were receiving opioids with minimal opioid side effects and had unrelieved neuropathic pain were enrolled in the study.
• A total of 63 patients completed the trial.
• Patients had a Karnofsky score higher than 60 and pain intensity rated as 4 or greater.
• Potential participants were excluded 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.

The study was conducted in Turkey.

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

• Pain intensity, specifically burning and shooting, was recorded with a numeric rating scale.
• The mean absolute change in pain intensity was recorded at day 13.
• Allodynia and analgesic drug consumption, including rescue, were evaluated at days 4 and 13. Side effects also were recorded.
• Allodynia was assessed by a light cotton material being stroked on painful and non-painful areas. Allodynia was said to be present if a normal response was noted in non-painful areas but pain or an unpleasant sensation was noted in the painful area.

Both groups (GO and OO) saw a significant reduction in pain intensity on days 4 and 13 compared to baseline. The mean pain intensity for burning or shooting pain was significantly higher in group OO compared to group GO at both assessment times (p = 0.0001); however, a clinically meaningful reduction was noted in group OO. In addition, a significant decrease in allogynia was seen in the GO group at day 4 (p = 0.002) and the rate of side effects was significantly lower in GO (p = 0.015). Of note, one patient in the GO group withdrew from the study due to respiratory depression. The patient was taking gabapentin and SR morphine and was age 66. Depression occurred three days after gabapentin was added.

The most frequent causes of pain included malignant sacral plexopathy (32%) in group GO and brachial plexopathy (28%) in group OO. Patients in the GO group remained at the same step of the ladder at day 4; group OO patients who took weak opioid at the second step all progressed to the third step. This may explain less SE in the GO group.

The findings suggest that gabapentin added to opioids provides better relief than opioid monotherapy alone and may represent a potential first-line treatment for these patients. Gabapentin added to opioids may create a synergistic effect. Gabapentin also may extend opioid efficacy.

• The measurement of allodynia was seen as a limitation, as were the primary neuropathic syndromes being different in each group.
• The World Health Organization ladder has been abandoned by many practitioners in favor of National Comprehensive Cancer Network or American Pain Society guidelines.

Nurses should be aware of possible respiratory depression when patients are treated with gabapentin and morphine, particularly older adult patients.