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Using gabapentin for the treatment of hot flashes in patients with breast cancer
A 900-mg daily dose of gabapentin significantly relieves vasomotor symptoms.
Symptoms of vasomotor instability plague most women undergoing breast cancer therapy. Many experience hot flashes. In addition, these women may also suffer from anxiety, irritability, palpitations, sweating and blotchy red skin. Further diminishing quality of life, night sweats can disturb natural sleep patterns. The symptoms range from mild disturbances to repetitive, drenching sweats that can last for months or years.
Hot flashes have a complex etiology. Chemotherapy, hormonal treatments or natural menopause have all been linked to the onset of symptoms. Some speculate that hot flashes occur from changes in the thermoregulatory center of the hypothalamus due to abrupt estrogen withdrawal. In many cases, a trigger causes a small change in the body temperature that leads to an exaggerated heat-loss mechanism resulting in the symptoms. Several neuroendocrine mediators, including norepinephrine, serotonin, estrogen, testosterone and endorphins, are likely involved in this reaction.
Estrogen replacement
Estrogen replacement therapy can effectively relieve hot flash symptoms, although the safety of estrogen in breast cancer patients has been debated. Many physicians believe that this therapy is contraindicated in women with breast, ovarian or uterine cancer. Progestational agents such as megestrol or medroxyprogesterone can relieve vasomotor symptoms in 75% of patients, but there are no long-term safety evaluations for these drugs in breast cancer patients.
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To make matters worse, it is difficult to assess therapeutic benefit for hot flashes because there is a strong placebo response, which points to the natural variability in symptom progressions. In controlled trials, 20% to 25% of women on placebo report a decrease in hot flash symptoms. Over the duration of a study, therapies that initially appear to be effective will not maintain those results. It is recommended that trials studying hot flash treatments be continued for 12 weeks. Unfortunately, most trials only last four to eight weeks.
Natural remedies
There are proponents of several herbal preparations like phytoestrogens, black cohosh, Chinese medicinal herb and red clover. The phytoestrogens found in soy products are weakly estrogenic compounds, making these products either no more effective or only slightly more effective than placebo. These compounds may also stimulate breast cancer cell growth and may antagonize the effect of hormonal therapies. Black cohosh preparations have also been advertised for symptom relief, but controlled trials have not shown them to be superior to placebo. Black cohosh has also been associated with reports of hepatic toxicity. Chinese medicinal herbs and red clover preparations have also not shown any benefit over placebo.
Antidepressants
Venlafaxine (Effexor, Wyeth) has been studied in the treatment of vasomotor symptoms for women with breast cancer. It acts as a serotonin receptor inhibitor at lower doses, and it inhibits norepinephrine reuptake at higher doses. Venlafaxine was shown to have a substantially greater reduction in hot flash symptoms than placebo, especially at a 75 to 100 mg daily dose. Common adverse events were dry mouth, decreased appetite, nausea and constipation. Unfortunately, this trial lasted for only six weeks.
A subsequent 12-week investigation with postmenopausal women, not breast cancer patients, did not show a difference in hot flash severity scores, but did show a significant improvement in subjective assessments of the effect of hot flash symptoms on daily living. Paroxetine may have similar effects to venlafaxine, but paroxetine could potentially interact with tamoxifen by reducing the active metabolite by its effects on CYP2D6. Fluoxetine does not appear to be as effective as venlafaxine or paroxetine.
One of the best responses has come from an analgesic, gabapentin. Related to gamma aminobutyric acid, gabapentin is used to treat many neurologic disorders. Originally developed as an anticonvulsant, it also has activity in the treatment of neuropathy, postherpetic neuralgia, bipolar disorder, migraines and many other disorders.
Analgesic
Pandya et al studied gabapentin therapy in 420 breast cancer patients who suffered from two or more hot flashes per day. Most of these patients were receiving tamoxifen. Chemotherapy patients were excluded. At the beginning of the study, participants reported a mean number of more than eight hot flash episodes per day. In this double-blind study, researchers randomized patients to three arms: 300-mg daily gabapentin, 900-mg daily gabapentin or placebo. Participants recorded their vasomotor symptoms one week before starting therapy and again at weeks 4 and 8. The three primary outcome measures were frequency, severity and duration of vasomotor symptoms. Results after eight weeks are shown in the table.
There were no statistically significant differences between the groups in the duration of vasomotor symptoms. Additionally, the differences in frequency and severity between the 300-mg group and the placebo group were not significant. The researchers concluded that the 900-mg dose of gabapentin was significantly superior to placebo in reducing the frequency and severity of hot flash symptoms in breast cancer patients. Somnolence and fatigue cause the most withdrawals.
Although the results were promising, this study closed after eight weeks. The long-term efficacy could not be established. However, gabapentin at a dose of 900 mg daily can be added to the available treatment options for the relief of vasomotor symptoms in breast cancer patients.
For more information:
- Hickey M, Saunders CM, Stuckey BG. Management of menopausal symptoms in patients with breast cancer: an evidence-based approach. Lancet Oncol. 2005;6:687-695.
- Molina JR, Barton DL, Loprinzi CL. Chemotherapy-induced ovarian failure: manifestations and management. Drug Saf. 2005;28:401-416.
- Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet. 2005;266:818-824.
About the author:
- Lisa K. Lohr, PharmD, is a clinical pharmacy specialist in oncology at Fairview University Medical Center in Minneapolis and is the section editor for pharmacology on Hem/Onc Today’s editorial board.