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.

DOI Link

Study Purpose

To examine the efficacy of two doses of venlafaxine:  37.5 mg (low-dose study) or 75 mg (high-dose study) to treat hot flashes after breast cancer.

Intervention Characteristics/Basic Study Process

Women were scheduled for 14 weekly visits. Weeks 1 and 2 provided baseline information, and weeks 3 to 14 included six weeks of treatment and six weeks of placebo.

Outcomes were hot flash (frequency, severity, and bother), hot flash impact on daily life, negative effect, fatigue, sleep, and quality of life (QOL).

Sample Characteristics

The sample was comprised of breast cancer survivors:  57 in the low-dose study and 20 in the high-dose study.

Setting

University cancer clinics in the southeastern and midwestern United States

Phase of Care and Clinical Applications

Patients were undergoing the long-term follow-up phase of care.

Study Design

The study included two randomized, double-blind, placebo-controlled, crossover trials.

Measurement Instruments/Methods

  • Adherence was measured by capsule counts and weekly written verification.
  • Sternal skin conductance monitor
  • Electronic event markers and written diaries used for self-reporting hot flashes
  • Profile of Mood States–Short Form (POMS-SF)
  • Positive and Negative Affect Scale (PANAS)
  • Center for Epidemiologic Studies Depression Scale (CESD)
  • Diagnostic and Statistical Manual of Mental Disorders (DSM)
  • Hamilton Rating Scale–Depression (HRSD)
  • Pittsburgh Sleep Quality Index (PSQI) 
  • Medical Outcomes Survey (MOS)

Results

Venlafaxine resulted in modest decreases in hot flashes, but only hot flash interference improved differentially at the higher dose. The timing of the effect of venlafaxine on hot flashes varied by dose.

Only women with a 50% or greater decrease in physiologic hot flashes experienced significant improvement in fatigue, sleep quality, and QOL. Although side effects were mild, most patients discontinued venlafaxine long-term.

Limitations

  • The sample was racially and ethnically homogeneous.
  • The study had a small sample size.
  • Treatment time was limited.
  • The study lacked pharmacogenetic data.
  • In assessing hot flashes, subjective hot flash measures are prone to placebo effects, and subjective hot flash measures and secondary outcome measures may both be subject to a positive reporting bias.
  • A study psychologist verified the absence of depressive symptoms, which could confound data if present.
  • Trained study nurses are required.