Elsevier

The Lancet

Volume 356, Issue 9247, 16 December 2000, Pages 2059-2063
The Lancet

Early Report
Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial

https://doi.org/10.1016/S0140-6736(00)03403-6Get rights and content

Summary

Background

Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer.

Methods

Participants were assigned placebo (n=56) or venlafaxine 37·5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37·5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks.

Findings

191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37·5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11–34), 37% (26–54), 61% (50–68), and 61% (48–75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75mg and 150 mg groups than in the placebo group.

Interpretation

Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.

Introduction

Hot flashes are a substantial problem in menopausal women. Oestrogen therapy is the mainstay of treatment for this symptom and generally controls hot flashes well.

Hot flashes may be more troublesome in women who have survived breast cancer1, 2 than in other women for several reasons. First, many women treated for breast cancer when premenopausal undergo premature menopause from chemotherapy. Second, many survivors of breast cancer are given tamoxifen, the most prevalent side-effect of which is hot flashes. Third, women with a history of breast cancer have generally been denied oestrogen therapy, at least in North America, because of concerns about potentiating recurrence of breast cancer.

Many agents have been investigated as potential means for alleviating hot flashes in survivors of breast cancer. The best-described non-oestrogenic treatments for hot flashes are progestagens. For example, low doses of megestrol acetate result in a reduction of about 80% in hot flashes, compared with a decrease of about 20% with placebo.3 At present, there are no convincing data that megestrol acetate has any substantial positive or negative effect on breast-cancer morbidity or mortality. Therefore, this therapy can reasonably be used after a thorough discussion of potential risks and benefits with the patient. Nonetheless, some patients and physicians are concerned about the use of any hormone in survivors of breast cancer. Thus, non-hormonal means to alleviate hot flashes in these patients are needed. Various non-hormonal therapies, including vitamin E, clonidine, Bellergal (phenobarbital, ergotamine, and levorotatory alkaloids of belladonna), and methyldopa, have been examined4, 5, 6, 7 but have limited efficacy or adverse side-effects.

On the basis of positive anecdotal experience, we undertook a pilot study of the antidepressant venlafaxine in cancer patients with hot flashes. The results supported the anecdotal experience.8, 9

We undertook this study to assess more definitively the efficacy and toxicity of various doses of venlafaxine for the treatment of hot flashes in survivors of breast cancer. The hypothesis was that venlafaxine would be effective in alleviating hot-flash activity. Planned subgroup analyses included an investigation into whether there was a dose-response relation, with control for potential confounding (mood change and quality of life).

Section snippets

Patients

Patients eligible for this trial were women who had a history of breast cancer or who were concerned about taking oestrogen for fear of breast cancer. Inclusion criteria were: troublesome hot flashes, occurring at least 14 times per week; flashes severe enough for the patient to desire therapeutic intervention, and present for at least a month before study entry; age older than 18 years; life expectancy at least 6 months; and performance status of 0–1 on the Eastern Cooperative Oncology Group

Results

229 patients joined this study between Feb 22 and July 27, 1999 (figure 1). Seven patients withdrew before taking any study medication and one patient was found to be ineligible. Hot-flash data for the baseline week were available for 207 patients (94%) and evaluable data over the whole study period for 191 (86%). The 30 patients who did not provide usable hot-flash data had stopped the study medications, did not properly complete or return the diary forms, or both.

At study entry the four

Discussion

This trial suggests that venlafaxine can alleviate hot flashes and that the most appropriate dose for this indication is 75 mg daily, which was more effective than 37·5 mg daily but was as effective as, and less toxic than, the 150mg dose. Thus, we recommend that treatment should start with a daily dose of 37·5 mg and be increased if necessary to 75 mg, but not higher. Some patients had substantial decreases in hot-flash activity with 37·5 mg venlafaxine daily. For those patients, there may not

References (29)

  • CL Loprinzi et al.

    Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer surivors

    J Clin Oncol

    (1998)
  • SL Pocock et al.

    Sequential treatment assignment with blancing for prognostic factors in the controlled clinical trial

    Biometrics

    (1975)
  • SK Quella et al.

    Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: an NCCTG trial

    J Clin Oncol

    (2000)
  • JA Sloan et al.

    Randomized comparison of four tools measuring quality of life in patients with advanced cancer

    J Clin Oncol

    (1998)
  • Cited by (699)

    • Menopause

      2023, Medical Clinics of North America
    • Evidence-Based Guidance for Breast Cancer Survivorship

      2023, Hematology/Oncology Clinics of North America
    • Management of Menopause Symptoms and Quality of Life during the Menopause Transition

      2022, Endocrinology and Metabolism Clinics of North America
    View all citing articles on Scopus
    View full text