A Placebo-Controlled Double-Blind Randomized Trial with Individualized Homeopathic Treatment Using a Symptom Cluster Approach in Women with Premenstrual Syndrome.

BACKGROUND: In a double-blind placebo-controlled randomized trial with parallel groups, the efficacy of individually prescribed homeopathic medicines was evaluated in women with premenstrual syndrome (PMS). METHODS: In an outpatient department of a university clinic in Jerusalem, Israel (1996-1999), women with PMS, aged 18 to 50 years, entered a 2-month screening phase with prospective daily recording of premenstrual symptoms by the Menstrual Distress Questionnaire (MDQ). They were included after being diagnosed with PMS. A reproducible treatment protocol was used: women received a homeopathic prescription based on symptom clusters identified in a questionnaire. The symptoms were verified during a complementary, structured, interview. Only women whose symptoms matched the symptom profile of one of 14 pre-selected homeopathic medicines were included. Each participant was administered active medicine or placebo via random allocation. Primary outcome measures were differences in changes in mean daily premenstrual symptom (PM) scores by the MDQ. Analysis was by intention-to-treat. RESULTS: A total of 105 women were included: 49 were randomized to active medicine and 56 to placebo. Forty-three women in the active medicine group and 53 in the placebo group received the allocated intervention with at least one follow-up measurement and their data were analyzed. Significantly greater improvement of mean PM scores was measured in the active medicine group (0.443 [standard deviation, SD, 0.32] to 0.287 [SD, 0.20]) compared to placebo (0.426 [SD, 0.34] to 0.340 [SD, 0.39]); p = 0.043. CONCLUSIONS: Individually prescribed homeopathic medicines were associated with significantly greater improvement of PM scores in women with PMS, compared to placebo. Replication, with larger sample size and other refinements, is recommended to confirm the efficacy of this treatment in other settings.

Electronic Registration in Complementary/Homeopathic Medical Practice with Identification of 'Best Homeopathic Cases': A Pilot Study.

BACKGROUND: Practice-based registration could identify 'general' and 'homeopathic' prognostic factors for therapeutic success in patients who seek complementary and alternative medicine (CAM)/homeopathic treatment. Identification of 'best homeopathic cases' within a database could inform clinical research and improve homeopathic practice. OBJECTIVE: To investigate the feasibility of registration in daily CAM/homeopathic practice, evaluate patient-reported outcome measures and tools for identifying 'best homeopathic cases' and to make recommendations for an electronic database. METHODS: In 2015 and 2016, 25 homeopathic doctors registered details of a maximum of 20 patients each, with 6 months of follow-up (extended follow-up for 'best homeopathic cases'), in Excel or in the Homeopathic Administration and Registration Program (HARP) database. Informed consent was obtained from each patient. Patient-perceived change of main complaint was measured by a 7-point Likert scale. Best homeopathic cases were defined by treatment with one homeopathic medicine, ≥ 2 months of follow-up, result score +2 to +4 on a 9-point Likert scale by the doctor, and by changes that could be attributed to the homeopathic medicine. Association between scores for change of main complaint and scores for 'best homeopathic case' was analysed by the Kruskal gamma test. RESULTS: Three-hundred and ninety-nine patients were included. In 49.1%, the main complaint was present for ≥ 2 years. The most common diagnosis was 'fatigue' (N = 56; 14%). Major improvement in the main complaint (score +3) was reported by 22 to 26% at consecutive follow-up visits. One-hundred and ninety-six patients were treated with a single homeopathic medicine, among whom 66 'best homeopathic cases' were identified. The correlation between patient-reported changes of main complaint and assessment by the doctor was significant (gamma = 0.832; p < 0.001). CONCLUSIONS: Registration of (co-)diagnoses, chronicity, treatments and outcomes in homeopathic practice with identification of 'best homeopathic cases' is feasible, using the tools provided. A user-friendly electronic database for efficient recording is recommended.

Semi-Individualized Homeopathy Add-On Versus Usual Care Only for Premenstrual Disorders: A Randomized, Controlled Feasibility Study.

OBJECTIVES: Premenstrual syndrome and premenstrual dysphoric disorder (PMS/PMDD) bother a substantial number of women. Homeopathy seems a promising treatment, but it needs investigation using reliable study designs. The feasibility of organizing an international randomized pragmatic trial on a homeopathic add-on treatment (usual care [UC] + HT) compared with UC alone was evaluated. DESIGN: A multicenter, randomized, controlled pragmatic trial with parallel groups. SETTINGS/LOCATION: The study was organized in general and private homeopathic practices in the Netherlands and Sweden and in an outpatient university clinic in Germany. SUBJECTS: Women diagnosed as having PMS/PMDD, based on prospective daily rating by the daily record of severity of problems (DRSP) during a period of 2 months, were included and randomized. INTERVENTIONS: Women were to receive UC + HT or UC for 4 months. Homeopathic medicine selection was according to a previously tested prognostic questionnaire and electronic algorithm. Usual care was as provided by the women's general practitioner according to their preferences. OUTCOME MEASURES: Before and after treatment, the women completed diaries (DRSP), the measure yourself concerns and well-being, and other questionnaires. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. RESULTS: In Germany, the study could not proceed because of legal limitations. In Sweden, recruitment proved extremely difficult. In the Netherlands and Sweden, 60 women were randomized (UC + HT: 28; UC: 32), data of 47/46 women were analyzed (ITT/PP). After 4 months, relative mean change of DRSP scores in the UC + HT group was significantly better than in the UC group (p = 0.03). CONCLUSIONS: With respect to recruitment and different legal status, it does not seem feasible to perform a larger, international, pragmatic randomized trial on (semi-)individualized homeopathy for PMS/PMDD. Since the added value of HT compared with UC was demonstrated by significant differences in symptom score changes, further studies are warranted.

Evaluation of a Prognostic Homeopathic Questionnaire for Women with Premenstrual Disorders.

BACKGROUND/AIMS: Validation of treatments with individually prescribed homeopathic medicines is a challenging task. A prognostic homeopathic patient questionnaire containing 140 keynote symptoms (highly characteristic of a specific homeopathic medicine) and an electronic algorithm to process the answers were used in 2 clinical studies. The algorithm outcome, based on total symptom scores, indicated 1 of 11 pre-selected homeopathic medicines for women with premenstrual syndrome and premenstrual dysphoric disorder (PMS/PMDD). Aims were (1) to estimate the prognostic values of keynote symptoms and (2) to evaluate the reliability of the homeopathic medicine ranking in the algorithm outcome. METHODS: The prevalence of specific keynote symptoms was calculated in 145 women diagnosed with PMS/PMDD and in 40 included women with favorable outcomes using 1 of the 11 homeopathic medicines. Likelihood ratios (LRs) of the keynote symptoms were calculated. Pearson's correlations were calculated between 2 sets of total algorithm scores for 11 homeopathic medicines, obtained at 2 time points. RESULTS: (1) A positive prognostic value (LR ≥ 1.5) was found in 34 keynote symptoms with a prevalence of 10-40%, with 10 symptoms already being connected to the corresponding homeopathic medicine in the algorithm. For example, the symptom 'common cold of the nose before menstruation' indicated Magnesium carbonicum with LR = 7.47 (confidence interval (CI) 3.90-14.28). (2) Pearson's correlations for the reliability evaluation varied from 0.69 to 0.84. CONCLUSIONS: Recommendations can be made to improve the PMS algorithm with more accurate keynote symptoms. The prognostic questionnaire proved a reliable tool to rank 11 homeopathic medicines by total scores, based on keynote symptoms. This PMS algorithm can be used for the treatment of PMS/PMDD in clinical practice.

Model validity of randomised placebo-controlled trials of non-individualised homeopathic treatment.

BACKGROUND: The comprehensive systematic review of randomised placebo-controlled trials (RCTs) in homeopathy requires examination of a study's model validity of homeopathic treatment (MVHT) as well as its risk of bias (extent of reliable evidence). OBJECTIVE: To appraise MVHT in those RCTs of non-individualised homeopathy that an associated investigation had judged as 'not at high risk of bias'. DESIGN: Systematic review. METHODS: An assessment of MVHT was ascribed to each of 26 eligible RCTs. Another 49 RCTs were ineligible due to their high risk of bias. MAIN OUTCOME MEASURES: MVHT and the prior risk of bias rating per trial were merged to obtain a single overall quality designation ('high', 'moderate', 'low'), based on the GRADE principle of downgrading. RESULTS: The trials were rated as 'acceptable MVHT' (N = 9), 'uncertain MVHT' (N = 10) and 'inadequate MVHT' (N = 7); and, previously, as 'reliable evidence' (N = 3) and 'non-reliable evidence' (N = 23). The 26 trials were designated overall as: 'high quality' (N = 1); 'moderate quality' (N = 18); 'low quality' (N = 7). CONCLUSION: Of the 26 RCTs of non-individualised homeopathy that were judged 'not at high risk of bias', nine have been rated 'acceptable MVHT'. One of those nine studies was designated 'high quality' overall ('acceptable MVHT' and 'reliable evidence'), and is thus currently the only reported RCT that represents best therapeutic practice as well as unbiased evidence in non-individualised homeopathy. As well as minimising risk of bias, new RCTs in this area must aim to maximise MVHT and clarity of reporting.