RESEARCH ARTICLE #homeopathy Individualized Homeopathic Treatment and Fluoxetine for Moderate to Severe Depression in Peri- and Postmenopausal Women (HOMDEP-MENOP Study): A Randomized, Double-Dummy, Double-Blind, Placebo-Controlled Trial Emma del Carmen Macías-Cortés1,2*, Lidia Llanes-González3, Leopoldo Aguilar-Faisal1, Juan Asbun-Bojalil1 1 División de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Distrito Federal, México, 2 Consulta Externa de Homeopatía, Hospital Juárez de México, Secretaría de Salud, Distrito Federal, México, 3 Unidad de Salud Mental, Hospital Juárez de México, Secretaría de Salud, Distrito Federal, México * ecmc2008@hotmail.es Abstract Background Perimenopausal period refers to the interval when women's menstrual cycles become irreg- ular and is characterized by an increased risk of depression. Use of homeopathy to treat de- pression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. Methods/Design A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depres- sion Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). PLOS ONE | DOI:10.1371/journal.pone.0118440 March 13, 2015 1/24 OPENACCESS Citation: Macías-Cortés EdC, Llanes-González L, Aguilar-Faisal L, Asbun-Bojalil J (2015) Individualized Homeopathic Treatment and Fluoxetine for Moderate to Severe Depression in Peri- and Postmenopausal Women (HOMDEP-MENOP Study): A Randomized, Double-Dummy, Double-Blind, Placebo-Controlled Trial. PLoS ONE 10(3): e0118440. doi:10.1371/ journal.pone.0118440 Academic Editor: Yiru Fang, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, CHINA Received: September 18, 2014 Accepted: January 13, 2015 Published: March 13, 2015 Copyright: © 2015 Macías-Cortés et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data are available upon request to the Research and Ethics Committee of National Homeopathic Hospital, Mexico City [Dr. Gustavo Aguilar-Velázquez ( gav5799@gmail.com

Results After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a sig- nificant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climac- teric Scale. Conclusion Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. Trial Registration ClinicalTrials.gov NCT01635218 Protocol Publication http://www.trialsjournal.com/content/14/1/105 . https://www.hri-research.org/wp-content/uploads/2015/03/Mac%C3%ADas-Cort%C3%A9s-2015-Depression-menopause.pdf