Efficacy of open-label placebos for premenstrual syndrome: a randomised controlled trial
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, r2=0.16) and interference (F(4)=3.159, p=0.014, r2=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][1] (submitted 2 May 2018).
Data are available in a public, open access repository. Meta-data is openly accessible on the data repository Harvard Dataverse. Upon reasonable request, relevant anonymised participant-level data will be made available.
[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03547661&atom=%2Febmed%2Fearly%2F2025%2F03%2F05%2Fbmjebm-2024-112875.atom
julian
Dr Susi Arnott
Lars Folkestad
Trish Greenhalgh
Claire Barnes