Introduction

Women with breast cancer who are treated with chemotherapy or hormonal therapy-i.e. Nolvadex® (tamoxifen)-commonly experience hot flashes, as well as other bothersome symptoms of premature menopause. Hot flashes have been reported in up to 65 percent of breast cancer survivors and they are severe in 59 percent of these women. The usual treatment for hot flashes is estrogen replacement therapy (ERT) or hormone replacement therapy (HRT), but both women who have had breast cancer and their physicians like to avoid these drugs because they may cause a recurrence of breast cancer.

Now breast cancer survivors who suffer from hot flashes have another option-low doses of commonly used antidepressants. Recent studies have shown that hot flashes are dramatically relieved by low doses of Effexor® (venlafaxine), Prozac® (fluoxetine), and Paxil® (paroxetine). The doses of these drugs that are effective in relieving the number and severity of hot flashes in breast cancer survivors are lower than those used to treat depression.

It is also possible that low doses of these antidepressants may be effective in treating hot flashes in postmenopausal women without breast cancer, but no studies have been conducted to confirm this theory. Low-dose antidepressant therapy may also prove helpful to men with prostate cancer who suffer hot flashes due to hormonal therapy. This hypothesis needs to be examined through further study.

"These antidepressants work well and are reasonably well-tolerated, so they represent an alternative therapy for women who do not want to take hormones," explained Charles L. Loprinzi, MD, of the Mayo Clinic in Rochester, Minnesota.

Dr. Loprinzi conducted two of the studies-the study using Effexor® and the study using Prozac®. V. Stearns, MD, and colleagues at Georgetown University School of Medicine in Washington, DC conducted a third study of Paxil®. Effexor® is a phenylethylamine-derivative, structurally unrelated to currently available antidepressants. Prozac® and Paxil® both belong to a class known as selective serotonin reuptake inhibitors (SSRIs).

The studies of Effexor® and Prozac® were double-blind, randomized trials; neither the women nor their physicians knew what drug they were taking until the end of the trial. In the study of Paxil®, the women and their physicians knew they were taking Paxil®, and results were based on information each woman entered in a "hot flash diary" and a health-related questionnaire that assessed their symptoms following the six-week study.

Effexor® Study

The largest study was conducted on Effexor® (venlafaxine), which included 229 women divided into four groups. The groups were randomly assigned to one of three doses of Effexor®-150 mg, 75 mg, or 37.5 mg-or to a placebo look-alike tablet. Treatment was continued for four weeks.

The best results in alleviating hot flashes were obtained with 75 mg per day of Effexor®. Women taking this dose over four weeks found that the number and severity of hot flashes was reduced by 61 percent compared to the beginning of the study.

Although this does not represent complete eradication of hot flashes, a two-thirds reduction offers a great deal of relief to women who suffer from them, explained Dr. Loprinzi.

Results also suggested that Effexor® 75 mg had additional benefits in increasing sex drive, improving depressed mood, and general quality of life. The mean change in libido scores was highest in the Effexor® 75 mg group compared to the other three groups, suggesting an improved sex life was possible. The depression score improved the most in that group, as well. All three doses of Effexor® improved patients' quality of life compared to placebo.

Effexor® was reasonably well-tolerated, said Dr. Loprinzi. A small number of patients experienced nausea, dry mouth, decreased appetite, and constipation. None of the other effects commonly seen with antidepressants were found, including diminished libido, dizziness, or agitation.

Dr. Loprinzi suggested starting treatment with Effexor®, 37.5 mg per day, and increasing it to 75 mg per day if it does not relieve the hot flashes.

Prozac® Study

Dr. Loprinzi was also the lead investigator of the Prozac® (fluoxetine) study that included 34 women with breast cancer. The women who enrolled in the trial experienced more than two bothersome hot flashes per day for at least a month and considered their hot flashes severe enough to want treatment for them. About half of the women were taking tamoxifen.

Women were randomized to receive either Prozac® 20 mg per day or a placebo look-alike tablet for four weeks. Then they were switched to the other treatment for an additional four weeks. Symptoms were rated by the women in a hot flash diary, noting the frequency and severity of each hot flash. The women who took Prozac® reported a 54 percent decrease in frequency of hot flashes and a 61 percent decrease in severity. On placebo, a 21 percent reduction in frequency and a 26 percent reduction in severity were observed. The effects of Prozac® and placebo were verified during the second four-week period of the study when the women switched treatment.

Paxil® Study

The Paxil® (paroxetine) study included 30 breast cancer survivors who were suffering at least two hot flashes a day related to prior chemotherapy treatment. There was no placebo group in this trial. The women were treated for one week with Paxil® 10 mg per day, and then received four additional weeks of treatment with a 20 mg daily dose of Paxil®. Throughout the study period, the women completed diaries related to their hot flashes as well as questionnaires about their symptoms and quality of life.

Twenty-seven women completed the study. The mean reduction in the frequency of hot flashes was 67 percent and the mean reduction in severity scores was 75 percent. These women also experienced a significant improvement in depression, the ability to sleep, anxiety, and quality of life scores. Twenty-five (83 percent) of the women decided to continue taking Paxil® after the study was completed.

The most common side effect was sleepiness, which caused two women to discontinue the drug and two additional women to have their daily dose reduced. One woman discontinued Paxil® due to anxiety.

Conclusion

These studies, as well as other preliminary studies, show that several of the SSRIs, such as Paxil® and Prozac®, in addition to Effexor®, are effective in treating chemotherapy-induced or tamoxifen-induced hot flashes in breast cancer survivors. The antidepressants used in these studies appeared to have benefits that extended beyond alleviating hot flashes-including improved mood, libido, and overall quality of life. All of the drugs were safe and well-tolerated.