Boekhout, A. H., Vincent, A. D., Dalesio, O. B., van den Bosch, J., Foekema-Tons, J. H., Adriaansz, S., . . . Schellens, J. H. (2011). Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 29(29), 3862-3868.

Evaluate the efficacy of venlaxafine and clonidine for hot flashes in patients with breast cancer

Patients were randomly assigned to receive 75 mg venlafaxine,  0.1 mg clonidine, or placebo daily.  Subjects were stratified by age, duration of hot flashes, concurrent endocrine therapy, and previous chemotherapy.   Patients were treated for 12 weeks.  Hot flash scores at week 12 were compared among the three groups.

N  80 AGE   Median = 49, range 28-71

MALES (%)          FEMALES (%)100%

KEY DISEASE CHARACTERISTICS 31% had age related symptoms, and 99% were post menopausal after breast cancer treatment.  52% received endocrine treatment
 

SITE  Multi-site  SETTING TYPE  Outpatient  LOCATION Netherlands

PHASE OF CARE Late effects and survivorship

 Double blind placebo controlled RCT

• Daily diary of frequency and severity of hot flashes - mild, moderate, severe categorization and calculation of daily hot flash scores
• Groningen Sleep Quality Index
• Hospital Anxiety and Depression Score
• Sexual Activity Questionnaire
   

Hot flash scores were lower in the clonidine group than the placebo group at week 12 ( p = .03), and lower in the venlaxafine group than placebo, though not statistically significant ( p = .07).  Over the 12-week period, reduction in the venlaxafine group was 41% ( P<.001), 26% in the clonidine group ( p=.045), and 29% in the placebo group (p<.001).  Those on venlaxafine tended to have some loss of appetite ( p = .003) as well as symptoms of nausea.  Sleep and sexual function were not different between the two treatment groups.  At week 12, anxiety and depression scores were higher in the venlafaxine than the clonidine group. (p = .03).  Significantly lower hot flash scores began in the venlafaxine group compared to placebo in weeks 1-4 (p =.01), and in the clonidine group, lower scores began compared to placebo in weeks 5-8 ( p = .04)

Both venlafaxine and clonidine were slightly more effective than placebo in reducing hot flash symptoms in this group of patients. However, over the 12 weeks, all study groups showed significant reduction in symptoms.

• Questionable protocol fidelity
• Other limitations/*explanation  Authors state that the final sample was underpowered.  It is noted that not all patients were compliant with the medications, but is not clearly stated how compliant they were or were not.  No information is given regarding any missing diary data, and reliability of diary and self-report of severity of hot flashes is not clear.  Follow up period was relatively short, so longer term efficacy is not clear.

Findings suggest that venlafaxine and clonidine may be of benefit in reducing hot flash symptoms in women with breast cancer. However, further research is needed for support, because placebo group also showed reduction in hot flashes. Some patients did have side effects from these medications; patients should be monitored for nausea, changes in appetite, anxiety, and depression if these medications are used.