Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain

Joseph Condon, M.D.

Augusto Caraceni, M.D., Ernesto Zecca, M.D., Cinzia Martini, M.D., and Franco De Conno, M.D. Journal of Pain and Symptom Management Volume 17, Number 6, June 1999

Many types of drugs have been used to control cancer pain including nonsteroidal anti-inflammatories, opiates as well as anticonvulsants. For neuropathic cancer pain, combination medication regimens may be more effective in enhancing analgesia. Specifically, gabapentin and other anti-seizure medications are often added to opiate regimens in order to produce increased efficacy of analgesia.

The above-noted study is a preliminary open-label non-controlled outcome study which attempts to evaluate the analgesic effect of adding gabapentin to a neuropathic cancer pain medication regimen. The null hypothesis is that adding gabapentin to the medication regimens used to treat neuropathic pain in cancer patients would not increase their analgesia. The independent variable is the addition of gabapentin to the previously working medication regimens. The dependent variable is the outcome variables of the study which include 0 to 10 scale measures of various components of neuropathic pain.

Twenty-two consecutive patients with neuropathic cancer pain (that was not completely controlled with opiate and analgesic management) were included in the study. Neuropathic pain was described as burning pain, paroxysmal episodes of shooting pain or pain with light touch, i.e., allodynia. Pain and side effect assessments were performed before starting gabapentin and 7 to 14 days of gabapentin therapy. The medication regimens, which the patients were on before starting gabapentin were kept unchanged. The assessment of pain was based on three 0 to 10 numerical scales and a yes or no response to the presence of allodynia.

Statistical analysis on the outcomes measures included calculation of confidence intervals and the Student's T test of paired samples as well as the Fisher Exact test for allodynia outcome.

The patient demographics diagnosis pain syndromes were recorded. A variety of cancer related pathologies were included in the patient's selection including brachial plexopathy, radiculopathy, and neuropathies. Certain patients also had metastasis to the bones. The global pain score decreased from a mean standard deviation of 6.4 (+/-) 1.5 to 3.2 (+/-) 1.3, which is a 95% confidence interval of pain score differences equaling 1.0 minus 2.4. Burning pain intensity decreased from a mean of 5.1 (+/- 3.6 standard deviation) to 2.0 (+/- 2.3 standard deviation), a 95% confidence interval of 1.5 minus 3.8. Episodes of shooting pain decrease in frequency from 7.2 (+/- 3.7) to 2.2 (+/- 2.2) with a 95% confidence interval of 1.8 minus 4.3. Allodynia was found in 9 patients and disappeared in 7 after gabapentin administration (P less than 0.01 with the Fisher's Exact test). Side effects due to the addition of gabapentin were minimal. The only reported change in side effects was one patient who had increased sedation with the addition of gabapentin. Another patient had new onset dizziness. Opioid-induced myoclonus decreased in one case.

Of note is the fact that the mean daily dose of gabapentin at time #1, which is when the second set of outcome measures were assessed, was 1,004 mg/day. It is interesting to note that a relatively impressive improvement in patient's neuropathic pain was achieved with a relatively low dose of gabapentin. Previous to this study it has been postulated that doses of greater than 1,000 mg were needed to achieve significant improvements in reported neuropathic pain.

Overall, the study demonstrates impressive reduction in reported neuropathic pain with the addition of gabapentin to patient's previous medication regimens. However, this study can only suggest that the addition of gabapentin to opiate regimens in the treatment of neuropathic cancer pain increases analgesic efficacy. This is mainly due to the lack of statistical power because of the small N-as admitted by the authors.

Another shortcoming of the study is no attempt to use a control group or to compare the efficacy of gabapentin against other anti-seizure medications, i.e., Topamax®, lamotrigine, Tegretol® or Dilanti®. These other medications have the advantage of once-a-day dosing and some of them are more cost effective than gabapentin. Unfortunately, this study cannot address the question of which anti-seizure medication might be most effective to add to medication regimens to control neuropathic cancer pain. The variety of cancer pathology included in the study also makes it impossible to determine whether one type of cancer pathology would respond to the addition of gabapentin more than another type of cancer pain etiology.

Obviously, a larger study would be required to answer some of these questions. The promising results of this study, however, do demonstrate the need for further research in this area and show that resources used for research into the addition of anti-seizure medications to medication regimens used to control cancer pain is warranted.

Joseph Condon, M.D.
Pain Management Fellow, 1999-2000
Department of Anesthesiology and Pain Management
University of California, Davis