In a double-blind, placebo-controlled trial, two often-prescribed treatments recommended in clinical guidelines for the management of hot flashes were found to be effective in managing hot flashes in patients with breast cancer. Patient-reported hot flash scores showed that venlafaxine, a selective serotonin reuptake inhibitor, induced a more immediate reduction of hot flashes, compared to clonidine, a centrally acting alpha-adrenergic agonist. At the end of the 12-week study, however, hot flash scores were lower in the women taking clonidine. The results were published in the Journal of Clinical Oncology.
A total of 102 women were enrolled from three hospitals in the Netherlands and randomly assigned to daily venlafaxine, clonidine, or placebo. Patients were instructed to keep a diary, recording the frequency and severity of hot flashes every day for the 2 weeks before administration of the study medications and the 12 weeks of the study treatment period. Patients were also asked to record weekly the frequency and severity of adverse events, including reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, abnormal sweating, and constipation. Week 12 data were available for analysis from 80 patients (78%)—35 in the venlafaxine group, 28 in the clonidine group, and 17 in the placebo group.
“During the 12th week of treatment, there was a reduction in hot flash scores by roughly 45% (two treatments combined) in comparison with placebo (P = .03), with no detectable difference between the two treatments (P = .58). Comparing clonidine with placebo, hot flash scores were significantly lower in the clonidine group at week 12 (P = .03); for venlafaxine vs placebo, the difference in hot flash scores was borderline not significant (P = .07),” the researchers reported.
Placebo Effect
“In contrast to the week 12 assessment, the reduction compared with placebo in hot flash scores over the entire 12-week period in the venlafaxine group was 41% (P = .001) and only 26% (P = .045) in the clonidine group,” the investigators stated. “In particular, hot flash scores decreased sooner after commencement of venlafaxine treatment than with clonidine treatment.” The authors also noted a substantial placebo effect, “with hot flash scores being reduced by 29% during the 12 weeks of treatment compared with baseline (P =. 001).”
Patients taking venlafaxine were more likely to experience nausea and constipation than those in the placebo group, and there was also a trend toward a higher incidence of appetite loss. At week 12, the anxiety score was higher in the clonidine group and the depression score was higher in the venlafaxine group.
The authors pointed out study limitations include the relatively small number of participants at week 12 and the reliance on self-reported data. “Thus it is hard to guarantee either the quality of the data or the objectivity.”
The researchers concluded that venlafaxine “resulted in a more immediate reduction of hot flash scores and was more effective in the management of hot flashes over 12 weeks of treatment. It is advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired.”
Boekhout AH, et al: J Clin Oncol. Sept. 12, 2011 (early release online).
