Carpenter, J.S., Storniolo, A.M., Johns, S., Monahan, P.O., Azzouz, F., Elam, J.L., … Shelton, R.C. (2007). Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer. Oncologist, 12, 124–135.

Examination of venlafaxine at two doses for efficacy in relation to physiologic and self-reported hot flashes and other outcomes

• Study duration: 14 weeks 
• Low-dose arm:  6 weeks at 37.5 mgof venlafaxine daily 
• High-dose arm: consisted of 1 week of 37.5 mg of venlafaxine daily, 4 weeks of 75 mg daily, and one week of 37.5 mg daily
• Weeks 1 and 2 provided baseline data 
• Weeks 3–14 included 6 weeks of treatment and 6 weeks of placebo

• Breast cancer survivors  recruited between 2000–2004 with follow up continuing through 2005 
• Must have been postmenopausal or using an approved method of birth control
• Low-dose study (n = 64, cancer clinics in the Southeast)
• High-dose study (n = 20, cancer clinics in the Midwest)

Outpatient cancer clinics

Randomized, double-blind, placebo-controlled crossover trial

A psychologist verified absence of depressive symptoms using two measures: Structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders and the 17-item Hamilton rating scale depression. Adherence to the treatment was assessed using capsule counts and weekly written verification. Physiologic hot flash frequency was evaluated using weekly 24-hour ambulatory sterna skin conductance monitoring and self-reported hot flash diaries. Weekly blood pressure monitoring and other tools were used for side effect monitoring.

Venlafaxine resulted in modest hot flash reduction, but only hot flash interference improved differentially at the higher dose. Timing of effects varied by dose. Only women who experienced a greater than 50% decrease in physiologic hot flashes also experienced a significant improvement in fatigue, sleep quality, and QOL. Although side effects were mild, most patients discontinued venlafaxine long term.

A placebo effect occurred for self-report of hot flashes but not for physiologic hot flashes in the high- and low-dose arms.

Main study limitations:

• Racially and ethnically homogeneous samples
• Limited treatment time
• Small sample size
• Lack of pharmacogenetic data. Also limitations regarding
• Assessing hot flashes with self-reporting is subject to placebo effects