Citalopram in Treating Postmenopausal Women With Hot Flashes

OBJECTIVES:

Primary

• Evaluate the efficacy of three different doses of citalopram hydrobromide on hot flash scores in postmenopausal women with a history of breast cancer or in postmenopausal women who do not wish to take estrogen replacement therapy for fear of increased risk of breast cancer.

Secondary

• Compare the side effect profile of these regimens in these patients.
• Compare the effects of these regimens on the secondary outcome of mood and interference with activities from hot flashes.
• Determine if CYP2C19 and CYP2D6 polymorphisms predict efficacy of various doses of citalopram hydrobromide.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18-49 years vs ≥ 50 years), tamoxifen (yes vs no), selective estrogen-receptor modulators (SERMs) (yes vs no), aromatase inhibitors (yes vs no), duration of hot flashes (< 9 months vs ≥ 9 months), and frequency of hot flashes per day (< 4 vs 4-9 vs ≥ 10). Patients are randomized to 1 of 4 treatment arms.

• Arm I (low-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in weeks 2-7.
• Arm II (medium-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in week 2 and 2 tablets once daily in weeks 3-7.
• Arm III (high-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in week 2, 2 tablets once daily in week 3, and 3 tablets once daily in weeks 4-7.
• Arm IV (placebo): Patients receive 1-3 placebo tablets once daily in weeks 2-7. All patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood collection periodically during study treatment for translational research studies.

A Symptom Experience diary is completed weekly and Profile of Mood States and Hot Flash-Related Interference Scale questionnaires are completed at baseline and in week 7.

DISEASE CHARACTERISTICS:

• Must meet 1 of the following criteria:

• History of breast cancer

• No current malignant disease
• No history of breast cancer and refused estrogen replacement therapy due to perceived increased risk of breast cancer
• Bothersome hot flashes, defined as hot flashes ≥ 14 times/week and of sufficient severity to make the patient desire therapeutic intervention
• Presence of hot flashes ≥ 1 month prior to study entry
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal, as defined by 1 of the following criteria:

• Absence of a menstrual period in the past 12 months
• Bilateral oophorectomy
• Absence of a menstrual period in the past 6 months with follicle-stimulating hormone (FSH) level > 40 mIU/mL
• ECOG performance status 0-1
• Life expectancy ≥ 6 months
• Willing to provide blood samples during study participation
• No history of allergic or other adverse reactions to citalopram hydrobromide or other selective serotonin reuptake inhibitors (SSRIs)
• No documented mania or hypomania

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior and no concurrent antineoplastic chemotherapy
• At least 4 weeks since prior and no concurrent androgens, estrogens, or progestational agents
• At least 3 months since prior antidepressant use, including Hypericum perforatum (St. John's wort)
• Concurrent tamoxifen, raloxifene, or aromatase inhibitors allowed if on a constant dose for ≥ 4 weeks and continuing medication during study period
• No other concurrent or planned agents for treating hot flashes (e.g., phenobarbital, megestrol, or clonidine)

• Stable dose of vitamin E allowed as long as it was started > 30 days prior to study entry
• Concurrent soy allowed
• Concurrent gabapentin allowed for reasons other than hot flashes if on a constant dose for ≥ 1 month and continuing during study period