Stearns, V., Slack, R., Greep, N., Henry-Tilman, R., Osborne, M., Bunnell, C., … Isaacs, C. (2005). Paroxetine is an effective treatment for hot flashes: Results from a prospective randomized clinical trial. Journal of Clinical Oncology, 23, 6919–6930.

The study assessed the  efficacy of paroxetine compared to placebo in reducing hot flashes in women with or without history of breast cancer.

There were four study arms:

• Arm A: four weeks of paroxetine 10 mg/day followed by four weeks of placebo 
• Arm B: four weeks of paroxetine 20 mg/day followed by four weeks of placebo
• Arm C: four weeks of placebo followed by four weeks of paroxetine 10 mg/day
• Arm D: four weeks of placebo followed by four weeks of paroxetine 20 mg/day

Women with or without history of breast cancer having at least 14 hot flashes per week were eligible, of whom 279 women were screened, and 151 were randomly assigned. 107 patients completed study. Mean age was 53 years. More than 80% had prior history of breast cancer, and 60% were taking an antiestrogen.

Inclusion criteria:

• Adult women with and without a prior history of breast cancer who could not or did not wish to take hormone therapy
• History of troublesome hot flashes occurring at least 14 times per week lasting 1 month or longe
• ECOG performance status of 0–2
• Creatinine and bilirubin less than two times normal level
• Vitamin E use for at least one month prior to study entry and continued through study period 
• Antiestrogen use for at least one month prior to study entry and continued through study period

Exclusion criteria: Concomitant use of cytotoxic chemotherapy, radiation therapy, estrogen or progesterone use, antidepressants, monoamine oxidase inhibitors, or treatments for hot flashes

The study was conducted in multi-institutional out-patient oncology clinics.

The trial was stratified, randomized, double-blind, cross-over, and placebo-controlled . Participants were stratified by age group (younger than 60 or older than 60) and antiestrogen use (yes or no).

Measures included:

• Hot flash daily diary
• QOL tools:
  • The Center for Epidemiologic Studies Depression Scale
  • Hospital Anxiety and Depression Scale (seven anxiety items)
  • Medical Outcomes Study (MOS)
    • Sleep Problems Index
    • Sexual Problems Index 
    • Overall health-related QOL questionnaire

Paroxetine 10 mg significantly reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively compared to 13.7% and 13.7% for placebo (p = .0006 and p = .0008, respectively). Paroxetine 20 mg significantly reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively compared to 26.6% and 28.8% for placebo (p = .002 and p = .004, respectively). Efficacy was similar between the two doses but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared to placebo (p = .01).

Study attrition was a limitation: 39 women did not complete 9 weeks of therapy; 26 women did not return diaries.