Strong placebo effect identified in studies of vasomotor symptom treatments

The placebo effect may play a role in the results of randomized controlled trials investigating medications for vasomotor symptoms, according to a meta-analysis published in Menopause.

“Normally, to seek approval from regulatory authorities, a treatment must demonstrate its efficacy and safety beyond placebo,” Tianyu Zhou, MD, MSc, of the development medical department at Astellas China Investment, wrote. “However, in placebo-controlled clinical trials, the reduction in the frequency of vasomotor symptoms could be up to 60% in the placebo arm. Previous research has found that placebo can even improve the symptoms of vasomotor symptoms when compared with no treatment. As a result, the need to control for placebo response often leads to additional considerations in study design, which incur higher costs for both subject screening and study operation.”

Zhou searched PubMed for placebo-controlled randomized trials that enrolled women with moderate to severe vasomotor symptoms (VMS) associated with menopause status who had at least seven or eight VMS episodes per day or at least 50 episodes per week. All 17 studies that met inclusion criteria measured treatment efficacy at 12 weeks.

Across all studies, the placebo arms demonstrated significant reductions in VMS frequency at 12 weeks, ranging from 7.2 to 4.16 episodes daily. The proportion of participants in placebo arms who experienced reductions in VMS frequency ranged from 34.4% to 66.7%.

Placebo effect estimation revealed the mean frequency of moderate or severe VMS at 12 weeks was reduced by 5.44 episodes per day (95% CI, 5.81 to 5.07).

Additionally, the placebo groups had a mean change in VMS severity at 12 weeks, ranging from 0.08 to 0.66. Among the 13 studies included for the estimation of VMS severity reduction, the placebo arms experienced significant decreases in severity (0.36; 95% CI, 0.46 to 0.27).

Of note, there was significant heterogeneity between studies for both the severity and frequency analyses.

“Although placebo effects may be utilized to bring about beneficial outcomes in clinical practices, these effects could be troublesome in clinical trials and even lead to unfavorable study results,” Zhou wrote. “In the case of the treatment of VMS, frequency and severity of VMS, as well as questionnaires assessing VMS-related quality of life, are widely used in clinical trials. Considering the potential placebo effect in the treatment of VMS, it can be a substantial obstacle for a new treatment that is seeking regulatory approval.”