A phase III trial evaluating three doses of citalopram for hot flashes: NCCTG trial N05C9

Abstract

9538 Background: Hot flashes are experienced by up to 75% of women and can negatively impact quality of life. Estrogen treatment has fallen out of favor, so new options are needed. Based on encouraging pilot data, this trial was designed to evaluate three doses of citalopram for effects on hot flashes. Methods: A randomized trial evaluated citalopram at doses of 10, 20 or 30 mg/day versus placebo for 6 weeks. Women recorded hot flashes for one week before starting treatment, then were titrated up to their assigned dose. The primary endpoint was change from baseline in hot flash score (frequency × severity) per a prospective daily hot flash diary. Secondary endpoints included hot flash frequency and activity interference. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. Eligibility included postmenopausal women with at least 14 bothersome hot flashes per week for the past month. A total of 50 patients per arm (N=200), provided 80% power for a two-sample t-test to detect a difference of 0.82 standard deviations or a drop of 29% from baseline in the hot flash score over placebo, with a 5% Type I error rate, including adjustment for multiple comparisons. Results: 254 patients were randomized onto this study. Data (below) for hot flash scores and frequency show improvement in hot flashes with citalopram with no significant differences among doses. Improvements were also seen for activity interference for all citalopram arms versus placebo (p<0.001). Patients on citalopram reported less distress related to hot flashes (p<0.001) and more satisfaction with hot flash control (p=0.02). Citalopram was well tolerated with no significant negative side effects. Conclusions: Citalopram is an effective, well tolerated agent in managing hot flashes. There does not appear to be a dose response above 10 mg/day. Arm Mean score reduction** P-values* Mean frequency reduction** P-values* Placebo 23% (CI: 11%-34% ) 20% (CI: 11%-30% ) 10 mg 49% (CI: 38%-60% ) p=0.0021 46% (CI: 36%-55% ) p=0.0004 20 mg 50% (CI: 39%-61% ) p=0.0011 43% (CI: 32%-53% ) p=0.0027 30 mg 55% (CI: 38%-73% ) p=0.0014 50% (CI: 38%-62% ) p=0.0002 * compared to placebo ** week 7-week 1 No significant financial relationships to disclose.