Abstract
OBJECTIVE: To investigate the efficacy and safety of open-label placebos (OLP) in premenstrual syndrome (PMS). DESIGN: Randomised controlled trial. SETTING: Switzerland, 2018-2020. PARTICIPANTS: 150 women (18-45 years of age) with PMS or premenstrual dysphoric disorder. INTERVENTION: Random assignment (1:1:1) to treatment as usual (TAU), OLP without treatment rationale (OLP-), or OLP with treatment rationale (OLP+). OLP consisted of two placebo pills per day for 6 weeks. MAIN OUTCOME MEASURES: Primary outcomes were PMS symptom intensity and interference between groups across three menstrual cycles (MC1-MC3); adverse events (ie, safety) were measured at weeks 3 and 6 after the start of the intervention. Secondary outcomes were psychological and somatic subscales of PMS symptom intensity, and adherence. RESULTS: From 2 August 2018 to 3 December 2020, 150 women were randomly allocated to TAU (n=50), OLP- (n=50), and OLP+ (n=50), of whom 145 (96.7%) completed trial participation. Groups differed in symptom intensity (F(4)=4.419, p=0.002, r(2)=0.16) and interference (F(4)=3.159, p=0.014, r(2)=0.13) across three MCs. Mean symptom intensity at MC3 was lower for OLP+ compared to TAU (b=-9.97, SE=2.85, t(412)=3.50, p<0.001, d=0.90) and to OLP- (b=-6.10, SE=2.89, t(411)=2.11, p=0.036, d=0.55), but OLP- and TAU did not differ (b=-3.87, SE=2.87, t(411)=1.35, p=0.177, d=0.35). Mean interference at MC3 was lower for OLP+ compared to TAU (b=-1.23, SE=0.54, t(443)=2.30, p=0.022, d=0.55) and to OLP- (b=-1.10, SE=0.54, t(442)=2.02, p=0.044, d=0.48), but OLP- and TAU did not differ (b=-0.14, SE=0.54, t(442)=0.26, p=0.799, d=0.06). Four non-serious adverse events were reported in OLP- (n=1) and OLP+ (n=3). Improvement in psychological and somatic symptom intensity was comparable to primary outcomes. Adherence to the OLP intervention was high (93.18±18.95%), with no difference between groups. CONCLUSIONS: The results of our clinical trial indicate that OLP provided with a treatment rationale is an effective, safe, and acceptable treatment for PMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03547661 (submitted 2 May 2018).