Kimmick, G.G., Lovato, J., McQuellon, R., Robinson, E., & Hyman, B.M. (2006). 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. Breast Journal, 12, 114–122.

This study assessed the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related QOL in women with breast cancer.

Patients were randomized to receive 50 mg sertraline each morning for six weeks, followed by six weeks of a placebo tablet each morning, or to six weeks of a placebo followed by six weeks of sertraline. Before starting the medication, a one-week pretreatment period was included during which patients recorded baseline measurements of hot flashes in a daily diary.

The study enrolled adult women with localized breast cancer (stages 0–IIIB) who were receiving adjuvant tamoxifen therapy and had at least one hot flash per day.

• Inclusion criteria: Normal hepatic function with total bilirubin of less than 2 mg/dl and aspartate aminotransferase (AST) greater than or equal to two times normal within six months of study entry.
• Exclusion criteria:
  • Women who were pregnant or breastfeeding; had a history of seizure disorder; hepatic or renal insufficiency.
  • Concurrent or planned therapy with estrogen, progestational agents, corticosteroids, androgens, or other antidepressant therapy.
  • Monoamine oxidase inhibitors or other SSRI use had to have been discontinued at least 14 days before entering the study.

The study was conducted in an oncology clinic in a tertiary care center.

This was a randomized, double-blind, placebo-controlled, crossover study.

Participants maintained a daily hot flash diary to record hot flash frequency and severity. Other instruments included:

• The Center for Epidemiologic Studies depression scale
• Functional Assessment of Cancer Therapy-Breast (FACT-B) 

Measurements were assessed at baseline, 6 weeks, and 12 weeks.

The baseline daily hot flash frequency and score were 5.8 and 11.5. At the end of six weeks, frequency of hot flashes decreased by 50% in a greater proportion of those taking sertraline than those in the control group. In crossover analysis, sertraline was significantly more effective that placebo: (p= 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 QOL were unchaged within treatment groups.

Limitations included:

• Small sample size less than 100
• Unable to detect statistically significant difference in the effect of sertraline versus placebo on hot flashes at six weeks