Loibl, S., Schwedler, K., von Minckwitz, G., Strohmeier, R., Mehta, K.M., & Kaufmann, M. (2007). Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients—A double-blind, randomized study. Annals of Oncology, 18, 689–693.

Compare venlafaxine to another nonhormonal agent in the treatment of hot flashes in patients with breast cancer

Patients were randomized to receive 0.075 mg clonidine twice daily or venlafaxine 37.5 mg twice daily for four weeks then crossover.

• Women with breast cancer experiencing hot flashes at least 14 times per week (N = 80). 64 patients completed study 
• Majority older than age 50 years 
• 40 randomized to each group.
  • 33 received clonidine, 31 received venlafaxine 
  • 9 stopped early because of side-effects
  • 7 withdrew
• Inclusion:
  • Adult women with primary breast cancer experiencing hot flashes at least 14 times per week or must have been seeking help for hot flashes. Hot flashes present at least four weeks before study entry.
  • Predefined menopausal status as not required.
  • Tamoxifen, gonadotropin-releasing agonists, and aldose reductase inhibitors  allowed as long as the patients had been on such therapy for at least a month and were planning to continue therapy during study.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Exclusion:
  • Previous treatment with venlafaxine and clonidine as well as estrogens, progestagens, or androgens for hot flashes
  • Current treatment with hypertensive or antidepressant agents, other nonhormonal agents for hot flashes such as black cohosh, isoflavones, and vitamin E 
  • Patients with hypertension or hypotension, peripheral or cardiovascular diseases, or symptomatic cardiac diseases

University hospital setting

Double-blind, randomized study

• Self-reported one-week hot flash and other symptom questionnaire assessed one week before start of treatment and end of treatment.
  • Hot flashes: frequency and severity
  • Symptoms assessed: Loss of appetite, mouth dryness, nausea, tiredness, constipation, restless sleep, nervousness, sweating, dizziness, mood disorder, diarrhea, sleeplessness

At end of week 4, the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes for those receiving clonidine (p = .025). Nausea was significantly greater with venlafaxine compared with clonidine. Mouth dryness, constipation, and restless sleep were reported more with clonidine but the difference was not statistically significant.

• Small sample size with less than 100 participants 
• Short follow-up period