Open-label placebo appears to reduce premenstrual symptoms, study suggests
Women affected by premenstrual syndrome (PMS) appear to experience less intense and debilitating symptoms after taking placebo pills even when told they do not contain any active medication, suggests a study published in the open-access journal BMJ Evidence-Based Medicine.
PMS can result in significant distress for women of reproductive age and cause psychological symptoms such as irritability, depressed mood, and mood swings as well as physical symptoms including breast tenderness, bloating, and joint pain.
Women with PMS are also more likely to feel suicidal, experience depression, have eating disorders and migraines.
Often prescribed medical treatments to help with PMS, such as selective serotonin reuptake inhibitors (SSRIs) and hormonal agents like oral contraceptives and danazol are often associated with side-effects including dizziness, nausea, tremor, weight gain, gastrointestinal symptoms, and depression.
Open-label placebos (OLPs) – placebos that are provided with full transparency – have been shown to have positive effects on various complaints, including irritable bowel syndrome, chronic low back pain, and menopausal hot flushes.
Researchers in Switzerland set out to examine whether these OLPs could have a positive impact on PMS symptoms.
They carried out a trial involving 150 women aged 18 to 45 years old who had PMS or premenstrual dysphoric disorder.
Between August 2018 and December 2020, the participating women were randomly allocated into three groups to receive treatment as usual, receive OLPs with no further explanation than that they were receiving placebos, or receive OLPs in pill form with an explanation of what they were and why OLPs could potentially ease PMS symptoms.
The researchers found that placebos reduced the intensity of PMS symptoms and interference in their social, educational and working lives considerably in women with moderate to severe PMS or premenstrual dysphoric disorder when they were provided with an explanation of the treatment.
For their study, they measured primary outcomes defined as PMS symptom intensity and interference in their lives between groups across three menstrual cycles, and safety by adverse events, measured at weeks 3 and 6 after the start of the intervention. They also measured secondary outcomes, which were psychological and physical subscales of PMS symptom intensity and adherence.
For the primary outcomes, placebos provided twice a day for 6 weeks with an explanation resulted in a 79.3% reduction in symptom intensity amongst these women and an 82.5% reduction in interference in their lives – underlining the importance of adequately providing the treatment explanation when giving placebos, said the researchers.
Women receiving a placebo with no explanation reported a 50.4% reduction in the intensity of their symptoms and a 50.3% drop in interference in their lives.
In contrast, women who received treatment as usual reported a 33% reduction in their symptom intensity and a 45.7% reduction in interference in their lives.
There were also very few and not serious side effects amongst women in both placebo groups.
For secondary outcomes, women in the placebo with explanation group had the highest decrease (70.7%) of psychological symptom intensity between menstrual cycles, followed by the placebo with no explanation group which reported a 42.6% fall in symptom intensity, compared with a decrease of just 29.1% in the women receiving treatment as usual.
Women in the placebo with explanation group also reported the highest reduction (82.5%) of physical symptom intensity between menstrual cycles, followed by women in the placebo with no explanation group (50.3%), and women in the traditional treatment group (45.7%).
The study had some limitations, with the authors acknowledging that when they advertised the trial as a study for a side-effect free intervention for PMS, they might have attracted participants who were more open to unconventional treatments and/or being dissatisfied with their current treatment, which could have limited how much the results were generalisable. Also, the results were reliant on self-reporting so this could bias the results.
Nevertheless, the researchers concluded: “Administering OLPs with a treatment rationale to women with PMS can decrease symptom intensity and interference considerably in the absence of substantial side-effects and with full transparency.
“Considering our results as much as the individual and societal burden of PMS, OLP treatment could serve as an acceptable, efficacious, and safe intervention for PMS.”
Reference:
Frey Nascimento A, Gaab J, Degen B, et alEfficacy of open-label placebos for premenstrual syndrome: a randomised controlled trialBMJ Evidence-Based Medicine Published Online First: 25 March 2025. doi: 10.1136/bmjebm-2024-112875
