A pragmatic, randomized controlled pilot study investigating the feasbility of an international study on individualized homeopathic add-on treatment and usual care only in women with premenstrual disorders

Worldwide, a meaningful proportion (8-32%) of women suffers from moderate to
severe premenstrual disorders. Moderate to severe PMS and Premenstrual
Dysphoric Disorder (PMDD) seem to be associated with impaired work productivity
and increased absenteeism, and thus pose a potential economic burden. At
present, evidence-based pharmacological treatments of women with PMDD and
severe PMS are the use of antidepressants of the Selective Serotonine Re-uptake
Inhibitors (SSRI)-type and the Combined Oral Contraceptive (COC)
drospirenone/ethinylestradiol. These treatments are often unsatisfactory and
women have reported to prefer more *natural and safe* treatment approaches.
A previous pilot study has shown that homeopathy may be a promising treatment
strategy to improve symptoms and quality of life of women who suffer from
premenstrual disorders. Therefore, we want to pilot the feasibility and effect
size (phase I) and investigate the possible added value (phase II) of a
well-defined previously tested homeopathic intervention compared to usual care.
The aim of phase I of this proposed pilot study is to investigate the
feasibility of an international pragmatic study on an individualised
homeopathic add-on treatment of women with premenstrual disorders and usual
care. In case the recruitment for to the pilot study goes according to plan,
the results are promising and implementation of the homeopathic treatment is
evaluated as feasible in the three countries, we will enter phase II of the
study. For phase II, additional women will be recruited and randomised. A new
sample size will be calculated based on the effect size of the pilot study, to
be able to detect possible significant differences between the
homeopathy-add-on and usual care group. For the homeopathic treatment we will
use a previously developed semi-standardised algorithm with 11 homeopathic
medicines. Women with premenstrual disorders will be recruited in the
Netherlands (NL), Sweden (S) and Germany (G). Women will be randomly assigned
to 4 months/cycles of homeopathic add-on treatment or usual care only.

Phase I: To investigate whether it is feasible to organize an international
multi-centre pragmatic trial on individualised homeopathic add-on treatment
using a semi-standardised algorithm in women with premenstrual disorders and
usual care only. We will describe the women*s preferences and expectations,
recruitment and the nature of usual care in the participating countries. We
will evaluate the adherence of the homeopaths and doctors to the study protocol
and the opinion of the homeopathic professionals in Sweden and Germany about
the semi standardised algorithm. We will measure effect size in both the usual
care group and the homeopathic add-on treatment group by calculating changes in
premenstrual symptoms, impact of health problems on social life and work
productivity, use of conventional medicines (e.g. sedatives, painkillers) for
premenstrual symptoms, disease-related costs and patient satisfaction. We will
assess and evaluate the changes in disease burden expressed as main concern and
well being as reported by the participants. We will evaluate the use of the
algorithm in daily homeopathic practice in Sweden and Germany.
Phase II: If the feasibility evaluation has positive results and preliminary
results tend to be in favour of homeopathy, we will additionally evaluate the
possible added value of individualised homeopathic add-on treatment in women
with PMD compared to usual care only in a larger sample of women.

A multi-centre, international, randomised, controlled pragmatic study with two
parallel groups

Usual care (UC): Depends on the treatment for PMS or PMDD that is usually
provided by the GP or specialist doctor. This can differ in each country and
between physicians in the same country, because there is no standard guideline
for treatment of PMS/PMDD. Usual care may include advice about nutrition and
lifestyle, vitamins, supplements, herbal products, OCPs, antidepressants, pain
medication and diuretics. Referral to a psychiatrist or gynaecologist is
possible.

Usual Care (UC) + Homeopathic add-on treatment (HT): In addition to usual care,
women will receive individualised homeopathic add-on treatment, using a
semi-standardized previously tested algorithm with 11 homeopathic medicines.

Women will receive 4 months/cycles of additional homeopathic treatment or usual
care only. Follow-up consultations will be scheduled after 2 and 4 menstrual
cycles. At follow-up consultations the physicians and homeopaths are allowed to
change the treatment according to their professional judgment and the woman*s
preferences.

Pulse, blood pressure, length and weight will be measured at intake and this
procedure will be repeated (except length) after termination.
Before, during and after the treatment the women will complete diaries and
questionnaires
Sometimes women will have to travel a bit further for the intake or the
homeopathic treatment (travel costs will be reimbursed)
The treatments are not burdensome. The homeopathic and usual treament are as
usual in daily practice.
Homeopathic treatments are reported as safe. In the usal care group medicines
could be advised that have side-effects. However, women will not be forced to
take those (or other) medicines.
We expect improvement of symptoms on both groups. Women who are randomised to
usual care will be offered the possibility to have homeopathic treatment after
4 months.
We expect that the benefits for the women will exceed the possible burdens.