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

Abstract

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.

Keywords

premenstrual syndrome - randomized - double-blind - placebo-controlled trial - homeopathy - individualized - symptom cluster

Highlights

• Homeopathic medicines proved superior to placebo in women with premenstrual syndrome.

• The use of active homeopathic medicines (compared to placebo) was also associated with more reduction in sick days and less use of other medication.

• A novel method called “the symptom cluster approach” was used for individualized homeopathic medicine selection for all women.

• This design with 14 homeopathic medicines enables replication of the treatment for future research or practice.

Authors’ Contributions

Michal Yakir (M.Y.) designed the study, was the principal investigator, drafted the initial protocol, looked after the participants, collected the data, analyzed and interpreted the results, and wrote the draft of the original report. George Vithoulkas (G.V.) proposed the questions for the homeopathic questionnaire. Zvi Bentwich supervised the study, assisted in writing the initial manuscript, was responsible (with G.V.) for generating grant support and (with M.Y.) for conceptualizing and designing the study. Shulamith Kreitler was responsible for the psychological tests and for some of the statistical analyses. Amnon Brzezinski was in charge of the gynecological clinic, provided the logistical support for the study, and gave expert gynecological advice. G.V. and M.O. served as homeopathic consultants. CKL revised and updated the draft manuscript in 2015-2017. All authors gave final approval of the article.

^* Previously, Hebrew University Hadassah Medical School, Jerusalem, Israel.

^** Previously, Department of Psychology (now called: School of Psychological Sciences), Tel Aviv University, Tel Aviv, Israel.

• References

• 1 Halbreich U, Backstrom T, Eriksson E. , et al. Clinical diagnostic criteria for premenstrual syndrome and guidelines for their quantification for research studies. Gynecol Endocrinol 2007; 23: 123-130
• 2 Yonkers KA, O'Brien PM, Eriksson E. Premenstrual syndrome. Lancet 2008; 371: 1200-1210
• 3 Marjoribanks J, Brown J, O'Brien PM, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev 2013; 7: CD001396
• 4 Lopez LM, Kaptein AA, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev 2012; 15: CD006586
• 5 Sundström-Poromaa I, Bixo M, Björn I, Nordh O. Compliance to antidepressant drug therapy for treatment of premenstrual syndrome. J Psychosom Obstet Gynaecol 2000; 21: 205-211
• 6 Gronich N, Lavi I, Rennert G. Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study. CMAJ 2011; 183: E1319-E1325
• 7 Lustyk MK, Gerrish WG, Shaver S, Keys SL. Cognitive-behavioral therapy for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review. Arch Women Ment Health 2009; 12: 85-96
• 8 Homeotherapy, paragraph 24-25 and The Simile, paragraph 26-34. In: Hahnemann S. Organon der Heilkunst (1810). Dutch translation 3rd edition by O.E.A. Goetze. Alkmaar, Homeovisie 1996: 14-19
• 9 Witt CM, Bluth M, Albrecht H, Weisshuhn TE, Baumgartner S, Willich SN. The in vitro evidence for an effect of high homeopathic potencies--a systematic review of the literature. Complement Ther Med 2007; 15: 128-138
• 10 Yakir M, Kreitler S, Brzezinski A, Vithoulkas G, Oberbaum M, Bentwich Z. Effects of homeopathic treatment in women with premenstrual syndrome: a pilot study. Br Homeopath J 2001; 90: 148-153
• 11 Yakir M. . Evaluating Homeopathic medicine: Clinical and Social Research with Premenstrual Syndrome (PMS) as a Case Study [PhD Dissertation, English version], Hebrew University, Jerusalem, 2002
• 12 Moos RH. The development of a menstrual distress questionnaire. Psychosom Med 1968; 30: 853-867
• 13 Kreitler S, Kreitler H. The cognitive orientation of suggestibility. A tool for predicting who will respond to suggestion (unpublished). Dept. of Psychology, Tel Aviv University; 1990
• 14 Rossi E, Bartoli P, Bianchi A, Endrizzi C, Da Frè M. Homeopathic aggravation with Quinquagintamillesimal potencies. Homeopathy 2012; 101: 112-120
• 15 Thompson E, Barron S, Spence D. A preliminary audit investigating remedy reactions including adverse events in routine homeopathic practice. Homeopathy 2004; 93: 203-209
• 16 Oberbaum M, Vithoulkas G, van Haselen R. Clinical trials of classical homeopathy: reflections on appropriate research designs. J Altern Complement Med 2003; 9: 105-111
• 17 Danno K, Colas A, Terzan L, Bordet MF. Homeopathic treatment of premenstrual syndrome: a case series. Homeopathy 2013; 102: 59-65
• 18 Komar T, Peck KS, Torline JR, Deroukakis M. A qualitative study to determine the efficacy of the homeopathic simillimum in the treatment of premenstrual syndrome. Am J Hom Med 2006; 99: 196-204
• 19 Klein-Laansma CT, Jansen JCH, van Tilborgh AJW, Van der Windt DAWM, Mathie RT, Rutten ALB. Semi-standardised homeopathic treatment of premenstrual syndrome with a limited number of medicines: feasibility study. Homeopathy 2010; 99: 192-204
• 20 Klein-Laansma CT, Jansen JCH, Van Tilborgh AJW, Van Vliet M. Evaluation of semi-standardized individualized homeopathic treatment of 77 women with premenstrual disorders: observational study with 9 months follow-up. Altern Integr Med 2014; 3: 164
• 21 Klein-Laansma CT, Jong M, von Hagens C, Jansen JPCH, van Wietmarschen H, Jong MC. Semi-individualized homeopathy add-on versus usual care only for premenstrual disorders: a randomized, controlled feasibility study. J Altern Complement Med 2018; 24: 684-693
• 22 Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J. Influence of context effects on health outcomes: a systematic review. Lancet 2001; 357: 757-762
• 23 Bensing JM, Verheul W. The silent healer: the role of communication in placebo effects. Patient Educ Couns 2010; 80: 293-299
• 24 Witt CM, Lüdtke R, Baur R, Willich SN. Homeopathic medical practice: long-term results of a cohort study with 3981 patients. BMC Public Health 2005; 5: 115