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Am Fam Physician. 2006;73(6):1100-1102

Hot flashes are among the most common symptoms reported by women during and after therapy for breast cancer. Conventional therapy for hot flashes using estrogen and progesterone has been reported to increase the risk of cancer recurrence, leading to a search for alternative therapies. Because the γ-aminobutyric analogue gabapentin (Neurontin) has been effective in controlling menopausal hot flashes, Pandya and colleagues studied the effectiveness of this medication in women with breast cancer.

They recruited 420 women with breast cancer through a community clinical oncology program. Study participants were 18 years or older and reported at least two hot flashes daily. Patients were not eligible if they were receiving chemotherapy, venlafaxine (Effexor), clonidine (Catapres), or anticonvulsant medication or if they had significant cardiac, cerebrovascular, or hepatic disease. Women with reproductive capacity were required to be using effective nonsteroidal contraception. Other medications, including tamoxifen (Nolvadex), were permitted. The women were randomly assigned to one of three intervention groups: a daily dosage of 300 or 900 mg of gabapentin or placebo all taken three times daily for eight weeks. During this time, participants recorded the occurrence and severity of hot flashes and maintained a symptom inventory in a diary during treatment.

The average age of participants was 55 years, and 95 percent were white. About 70 percent of women in each group were using tamoxifen, and 9 percent had undergone chemotherapy. At baseline, the three groups were almost identical in the average number of hot flashes per day, the perceived severity of flashes, and the duration of episodes. At eight weeks, data were available on 347 women. Similar numbers of women withdrew from each of the intervention groups, but the reasons for discontinuation were different. Nine women receiving gabapentin withdrew because of fatigue or similar symptoms and seven because of lack of effect. Conversely, one patient receiving placebo withdrew because of fatigue but seven cited lack of impact on symptoms. The frequency and severity of hot flashes declined in all three groups but only achieved statistical significance in women treated with 900 mg gabapentin (see accompanying table). From baseline, this group reported a mean reduction of 44 percent in occurrence of hot flashes and a 46 percent reduction in severity. The comparable figures for placebo and 300 mg gabapentin were 15 and 30 percent for frequency and 15 and 31 percent for severity, respectively. These results were not influenced by adjustment for age and tamoxifen use.

OutcomeChange (95% confidence interval) from baseline to week 8
Placebo (n = 113)Gabapentin (Neurontin) 300 mg (n = 114)Gabapentin 900 mg (n = 120)P*
Mean change−2.25 (−3.33 to −1.17)−2.86 (−3.84 to −1.88)−4.21 (−5.00 to −3.42).0002
Percentage change−15 (−28 to −2)−30 (−39 to −21)−44 (−53 to −35).0006
Mean change−1.20 (−2.01 to −0.39)−1.80 (−2.59 to −1.01)−1.17 (−1.74 to −0.60).215
Percentage change1 (−13 to 15)−12 (−30 to 6)−9 (−26 to 8).589
Mean change−6.61 (−9.68 to −3.54)−7.75 (−11.2 to −4.35)−9.94 (−12.0 to −7.85).002
Percentage change−15 (−29 to −1)−31 (−46 to −16)−46 (−58 to −34).007

The authors conclude that gabapentin at dosages of at least 900 mg is effective in reducing symptoms of hot flashes in women with breast cancer. These results correlate with studies in postmenopausal women indicating that higher dosages of gabapentin are required for clinical effect. In this study, the reductions obtained with gabapentin are somewhat lower than those reported with other agents, but gabapentin may have advantages over other treatments because it does not inhibit cytochrome P450 enzymes that are significant in the metabolism of tamoxifen and other drugs.

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