Gabapentin is in a class of medications called anticonvulsants. Gabapentin treats seizures by decreasing excitement in the brain. Gabapentin has been studied for its effect in patients with cancer who have neuropathic pain or symptoms of peripheral neuropathy. Its effect occurs by changing the way the body senses pain. It has also been studied for its effect on anxiety and hot flashes. Gabapentin in combination with other medications such as opioids and impramine have been studied for effects on neuropathic pain and other symptoms.
The U.S. Food and Drug Administration (FDA) has issued a warning regarding the use of gabapentin or pregabalin and serious breathing difficulties in people with respiratory risk factors, including older adults, those having conditions that reduce lung function such as chronic obstructive pulmonary disease (COPD), and those using drugs that depress the central nervous system including opioids, anti-anxiety medication, antidepressants, and antihistamines.
Hershman, D.L., Lacchetti, C., Dworkin, R.H., Lavoie Smith, E.M., Bleeker, J., Cavaletti, G., . . . American Society of Clinical Oncology. (2014). Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. Journal of Clinical Oncology, 32, 1941–1967.
STUDY PURPOSE: To provide evidence-based guidance on optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy in adult cancer survivors
TYPE OF STUDY: Systematic review
DATABASES USED: Ovid Medline (1946–April, week 2, 2013); EMBASE (1980–2013, week 16); AMED Allied and Complementary Medicine (1985–April 2013)
KEYWORDS: chemotherapy-induced peripheral neuropathy; adult cancer survivors; randomized clinical trials
INCLUSION CRITERIA: Adult cancer survivors with chemotherapy-induced peripheral neuropathy; randomized trials
EXCLUSION CRITERIA: Phase 1 trials; published in a language other than English; less than 10 patients; focused on radiation or stem cell transplant neuropathy; animal studies
TOTAL REFERENCES RETRIEVED = 1,252
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: An expert panel representing neurology, nursing, medical oncology, community oncology, pain research, and genetics met through teleconference and emails to review and develop the American Society of Clinical Oncology guidelines.
PHASE OF CARE: Active antitumor treatment
Forty-two randomized clinical trials involved 19 various interventions for prevention of chemotherapy-induced peripheral neuropathy. These agents included anticonvulsants, antidepressants, vitamins, minerals, and other chemoprotectant drugs. Only six randomized clinical trials discovered six different drugs, such as antidepressants, anticonvulsants, and a topical gel, for the prevention of chemotherapy-induced peripheral neuropathy. The following are not recommended for use: acetyl-l-carnitine, amifostine, amitriptyline, calcium and magnesium, glutathione, nimodipine, ORG 2766, trans retinoic acid, rhuLIF, and vitamin E. Venlafaxine is not recommended for routine use in clinical practice. Although data support potential utility, evidence is not strong enough to suggest use. For treatment of chemotherapy-induced peripheral neuropathy, clinicians can offer duloxetine. No recommendation is made regarding ALC. Tricyclic antidepressants or gabapentin through trial use may be reasonable. The panel felt that trying topical gel containing baclofen, amitriptyline, and ketamine would be reasonable.
No agents were recommended for the prevention of chemotherapy-induced peripheral neuropathy, but duloxetine is moderately recommended for the treatment of chemotherapy-induce peripheral neuropathy. Even though conclusive evidence is lacking to recommend tricyclic antidepressants such as nortriptyline, gabapentin, and a topical gel containing baclofen,amitriptyline, and ketamine for treatment of chemotherapy-induced peripheral neuropathy, the expert panel agreed that offering these agents based on treatment for neuropathic pain is reasonable. The panel also recommended that patients be counseled regarding the lack of evidence in treating chemotherapy-induced peripheral neuropathy with these agents.
Nurses are at the frontline in assessing patients who are receiving agents with the potential for chemotherapy-induced peripheral neuropathy. Nurses should be aware of the standard of care in treating this population. Many drugs prescribed have no evidence in preventing or treating these patients. However, with these American Society of Clinical Oncology guidelines, a role for duloxetine is clear and a role for tricyclic antidepressants is possible. Nurses need to be knowledgeable about this information to better inform patients.
Jongen, J.L., Huijsman, M.L., Jessurun, J., Ogenio, K., Schipper, D., Verkouteren, D.R., . . . Vissers, K.C. (2013). The evidence for pharmacologic treatment of neuropathic cancer pain: Beneficial and adverse effects. Journal of Pain and Symptom Management, 46, 581–590.e1.
STUDY PURPOSE: To evaluate the evidence regarding beneficial and adverse effects of pharmacologic treatment of neuropathic cancer pain
TYPE OF STUDY: Systematic review
DATABASES USED: PubMed and EMBASE before August 2012; additional studies were identified from study reference lists.
KEYWORDS: Complete search terms are provided.
INCLUSION CRITERIA: Studies involving adult patients with cancer receiving oral analgesics
EXCLUSION CRITERIA: Not specified
TOTAL REFERENCES RETRIEVED = 653
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: American Academy of Neurology evidence classification was used. Authors calculated the absolute risk benefit as the number of patients who received 30%–50% improvement divided by the total number of patients in the treatment group. The fraction of patients who dropped out because of adverse events also was determined. Pain reduction scores were calculated as the percentage of pain reduction from baseline in the study.
APPLICATIONS: Palliative care
The proportion of patients who obtained improvement of pain with antidepressants was 0.55 (95% CI 0.40–0.69), with anticonvulsants was 0.57 (95% CI 0.44–0.69), with opioids was 0.95 (95% CI 0.93–0.96), and with other adjuvant medications was 0.45 (95% CI 0.33–0.57). Effects for patients with mixed pain were similar. The proportion of patients who withdrew because of adverse effects was 12.6% with antidepressants, 5% with anticonvulsants, 6% with opioids, and 6% with other adjuvant medications.
A substantial proportion of patients achieved pain reduction with adjuvant pain medications, and the proportion of patients who had benefit was higher than those who had to withdraw from studies because of adverse effects. The highest benefit was seen with opioids.
Numerous limitations in this review make it difficult to evaluate the relative benefits of various approaches evaluated for management of neuropathic pain. Findings do suggest that results with all types of coanalgesics used appear to have benefits that outweigh the prevalence of adverse effects. Findings continue to support the effect and benefits of opioids as a mainstay of pain management for mixed and neuropathic pain.
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 evaluate the effectiveness of low-dose gabapentin combined with imipramine, in treating cancer-related neuropathic pain
Patients were allocated to four groups. Group 1, consisting of 14 patients, received gabapentin 200 mg and imipramine 10 mg orally every 12 hours; Group 2, consisting of 14 patients, received gabapentin 200 mg orally every 12 hours; Group 3, consisting of 12 patients, received gabapentin 400 mg orally every 12 hours; and Group 4, consisting of 12 patients, received imipramine 10 mg orally every 12 hours. The average intensity of total pain over the past 12 hours was assessed, and the number of paroxysmal pain episodes in the past 24 hours were recorded. Pain was assessed at the first visit and seven days after the beginning of the regimen. Opioid rescue doses were available if needed.
Randomized, controlled trial
Pain was measured on a numeric scale, 1–10.
The total pain scores and daily paroxysmal pain episodes of the patients taking the low-dose gabapentin-imipramine combination (Group 1) decreased significantly (p < 0.05). The combination significantly decreased the previous 24-hour opioid rescue dose. Researchers observed mild adverse symptoms in all four groups. Symptoms included drowsiness, dizziness, and nausea. Note: Three patients dropped out of Group 3 because of adverse effects.
The combination of gabapentin and imipramine in low doses offers a means of successfully treating neuropathic pain, with minimal side effects.
The gabapentin-imipramine combination is effective in treating neuropathic pain caused by nerve compression or invasion of the spinal cord.
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.
The study was conducted in Turkey.
The study was a randomized, single-site, open trial.
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.
Nurses should be aware of possible respiratory depression when patients are treated with gabapentin and morphine, particularly older adult patients.
Patarica-Huber, E., Boskov, N., & Pjevic, M. (2011). Multimodal approach to therapy-related neuropathic pain in breast cancer. Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology, 16, 40–45.
The purpose of the study was to evaluate the effects of gabapentin with nonsteroidal anti-inflammatory drugs (NSAIDs) and morphine versus gabapentin alone.
Participants were randomized into three groups. Group 1, consisting of 25 participants, received gabapentin alone, titrated weekly from 300 mg per day to 3,600 mg per day in divided doses. Group 2, consisting of 25 participants, received gabapentin 1,200 mg per day and diclofen 100 mg per day, also titrated over the first week. Group 3, consisting of 25 participants, received gabapentin 900 mg per day, diclofen 100 mg per day, and morphine 60 mg per day all in divided doses. Patients were treated for six weeks and assessed on a weekly basis.
This single-site study was conducted in an outpatient setting in Serbia.
Phase of care
Applications
This study was quasiexperimental.
Participants in all three groups saw diminished pain and diminished influence of pain on their daily activities. No significant difference was noted between groups (p = 0.05).
Although all groups achieved significant pain control, the authors concluded that the multimodal therapy used in group 3 provided the best pain relief with the fewest side effects. However, inconsistency existed regarding doses between groups and, although differences in pain levels in each group diminished over time, between-group differences were not significant. No firm conclusions can be made.
The results support a multimodal approach to pain management in patients with breast cancer with neuropathic pain, but are not specific to peripheral neuropathy. The findings do not suggest any difference between the treatments tested in terms of efficacy; however, multiple limitations did exist in the study.
National Comprehensive Cancer Network.( 2011). NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain [v.2.2011]. Retrieved from http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
NCCN categories of evidence and consensus are described. Unless otherwise stated, all recommendations are reported to be category 2A, indicating a low level of evidence and uniform NCCN consensus. Specific process for evidence rating and consensus development is not described in the document. In addition, a search strategy was not described.
The NCCN guidelines document recommends universal screening for pain and provides an algorithm for comprehensive assessment and management approaches based on etiology of pain and current status with regard to pharmacologic management.
For opioid-naïve patients:
For opioid-tolerant patients:
For all cases, recommendations include:
For specific pain syndromes:
The major limitations of these guidelines are:
The NCCN guidelines document provides comprehensive decision making algorithms for assessment, severity grading, and management of cancer-related pain. The guidelines also provide assessment tools, titration schedule examples, and conversion tables for medications and conversion to transdermal fentanyl. An additional offering are suggestions regarding the management of a variety of opioid adverse effects. (A trial of adjunctive medications are suggested for neuropathic pain as a pain management approach.)