Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Sertraline (Zoloft) for the Treatment of Hot Flashes in Women with Early Stage Breast Cancer Taking Tamoxifen

Abstract

We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related quality of life. We used a randomized, double-blind, placebo-controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency x severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy--Breast (FACT-B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty-two women were accrued. Forty-seven women (median age 53.9 years, range 36.6-77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (-0.9 and -1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted.

Early discontinuation of tamoxifen

“…The selective serotonin reuptake inhibitor (SSRI) and selective serotonin-norepinephrine reuptake inhibitor (SSNRI) antidepressant classes have been used successfully to reduce the frequency and severity of vasomotor symptoms associated with breast cancer and tamoxifen use. [40][41][42][43] It is therefore possible that concomitant use of tamoxifen and certain SSRIs/SNRIs could improve tamoxifen persistence by minimizing side effects. Whether women continued with or commenced antidepressant use after initiation of tamoxifen was not recorded for this study and as a result it is not possible to draw conclusions about the effect of concurrent antidepressant use on tamoxifen persistence.…”

Recent Developments in Pharmacotherapy for Vasomotor Symptoms

“…Initial studies were largely undertaken in breast cancer survivors, and the number and severity of VMS were less than the standards required by the US Food and Drug Administration (FDA) and utilized in randomized controlled studies of hormone therapies [32][33][34][35][36]. Efficacy in reducing the number and severity of VMS averages around 65% with SSRIs like fluoxetine (20 mg/d) and paroxetine (12.5-25 mg/d), and an SNRI like venlafaxine (37.5-75 mg/d).…”

Centrally active nonhormonal hot flash therapies

“…11 Findings from pilot trials of 2 other newer antidepressants, mirtazapine and citalopram, suggested that they also are efficacious and well tolerated. 27,28 Nonetheless, significant efficacy was not reported in a recent trial that looked for long-term effects of fluoxetine and citalopram, compared with placebo, in 150 postmenopausal women with hot flashes.…”

“…There are several centrally acting compounds that have been investigated as a means of alleviating hot flashes in women ( Table 1). [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Potential mechanisms for their efficacy have been described in detail. 15 The present article delineates the histories of several of these classes of agents in the order in which they were first investigated.…”