Clinical trial NCT05346445: Comparison of Fluoxetine Versus Citalopram Therapy to Control Postmenopausal Vasomotor Syndrome
Official title: Citalopram Improves Vasomotor and Urogenital Syndromes in Mexican Patients With Post-menopause
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopause
Hot Flashes
Keywords: Postmenopause
Fluoxetine
Menopause Rating Scale
Vasomotor syndrome
Urogenital syndrome
Citalopram
Non hormonal therapy
Non-hormonal therapies
Serotonin reuptake inhibitors
Lead sponsor: Hospital Regional 1o de Octubre
Sponsor class: OTHER
Collaborators: name: Universidad Nacional Autonoma de Mexico
name: National Polytechnic Institute, Mexico
First posted: 2022-04-26
Enrollment: 91
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study was a prospective randomized clinical trial made in Mexican women diagnosed with postmenopause from the climacteric clinic of the regional hospital "1ro de Octubre-Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE)". Eligible participants were randomly selected in each consult to receive citalopram 20 mg/d or fluoxetine 20 mg/d for six months. The evaluation of the MRS score was done at the first consult and three and six months after medication. The institutional ethical committee of the hospital approved the study on May 20th, 2021, with registration number CONBIOETICA-09-CEI-012-20170421 and the internal registration number 122.2021. All participants provided written informed consent.
Primary purpose: TREATMENT

Brief summary: This study determined the efficacy of non-hormonal therapy with citalopram compared to fluoxetine, for the treatment of menopausal symptoms in Mexican women with vasomotor syndrome (VMS) and urogenital syndrome.

Detailed description: Women's reproductive life goes through a senescence process called transition to menopause, which generates an imbalance in estrogenic hormonal regulation that is more evident between the fifth and sixth decades of life. This condition allows the passage from an active reproductive stage to an inactive one, which triggers an adaptative physiological response to the reduction of estrogens. However, the progressive depletion of estrogen levels causes clinical signs and symptoms in the central nervous system, metabolism, musculoskeletal apparatus, urogenital system, and skin. These symptoms lead to disability, work absenteeism, and health costs, affecting the quality of life of women in this stage. Vasomotor symptoms are the main clinical manifestation for which women seek treatment. Vasomotor syndrome (VMS) occurs in 75 to 80% of all women. The first-line management of menopausal symptoms is hormone replacement therapy (HRT). However, some patients present adverse effects or contraindications for using it.

The aim of this study was to determine the efficacy of the citalopram for treating menopausal symptoms in Mexican women with vasomotor syndrome (VMS) and urogenital syndrome.

This study was a prospective randomized clinical trial, where 91 post-menopausal participants with severe baseline scores on the Menopause Rating Scale (MRS) were randomly selected and treated with citalopram (n=49) or fluoxetine (n=42). Changes from baseline MRS score at three and six months of treatment were evaluated.

Participants were randomly assigned to groups before each consult. Randomization was done using RAND and RANK functions from Excel-Word to generate unique random numbers for every participant´s ID. Fluoxetine is the Gold Standard treatment in Mexico, whereby it was used as the control medication. Loading doses of citalopram 20 mg orally or fluoxetine 20 mg orally were administrated.

Statical analysis was performed using PAST 3.0 and GraphPad Prism 8.4.3. software. Some statical parameters, such as arithmetic median (µ), standard deviation (S.D.), and Hazard ratio, were calculated using Excel-Word. Graphics were constructed with GraphPad Prism 8.4.3. Tables and Forest plots were done in Excel-Word. Odds ratio (OR), Relative Risk (RR), and chi-squared were calculated with PAST 3.0 software. The assigned α value for this study was \<0.05.

Eligibility criteria: Inclusion Criteria:

* Participants who attended the climacteric consultation for the first time, without prior treatment of menopausal symptoms, and who met postmenopausal criteria.
* Participants who met the criteria for vasomotor syndrome and score greater than 17 points in total MRS.
* Participants without psychiatric pathology (psychiatric illnesses such as major depression, generalized anxiety disorder, among others).
* Participants who agreed to participate and gave their written informed consent.

Exclusion Criteria:

* Participants who had contraindications to receive serotonin reuptake inhibitors (SSRIs).
* Participants who were receiving prior treatment for the postmenopausal or vasomotor syndrome.
* Participants who did not agree to participate or sign the informed consent.

Primary outcomes:
measure: Change from baseline Menopause Rating Scale (MRS) total score at 3 months
timeFrame: 3 months
measure: Change from baseline Menopause Rating Scale (MRS) total score at 6 months
timeFrame: 6 months
measure: Change from baseline Menopause Rating Scale (MRS) somatic domain score at 3 months
timeFrame: 3 months
measure: Change from baseline Menopause Rating Scale (MRS) somatic domain score at 6 months
timeFrame: 6 months
measure: Change from baseline Menopause Rating Scale (MRS) urogenital domain score at 3 months
timeFrame: 3 months
measure: Change from baseline Menopause Rating Scale (MRS) urogenital domain score at 6 months
timeFrame: 6 months
measure: Change from baseline Menopause Rating Scale (MRS) psychological domain score at 3 months
timeFrame: 3 months
measure: Change from baseline Menopause Rating Scale (MRS) psychological domain score at 6 months
timeFrame: 6 months
measure: Change from baseline score in Item 1 of the Menopause Rating Scale (MRS) at 3 months
timeFrame: 3 months
measure: Change from baseline score in Item 1 of the Menopause Rating Scale (MRS) at 6 months
timeFrame: 3 months
Secondary outcomes:
measure: Change from the severity of individual Menopause Rating Scale (MRS) items at 6 months
timeFrame: 6 months
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE
Study officials:
affiliation: Tissue Bioengineering Laboratory, National Autonomous University of Mexico [UNAM]
name: Juan M Ocampo-Godinez, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE
name: Patricia Loranca-Moreno, M.D., M.Sc.
role: STUDY_DIRECTOR
affiliation: Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE
name: Alan Rios-Espinosa, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: El Khoudary SR, McClure CK, VoPham T, Karvonen-Gutierrez CA, Sternfeld B, Cauley JA, Khalil N, Sutton-Tyrrell K. Longitudinal assessment of the menopausal transition, endogenous sex hormones, and perception of physical functioning: the Study of Women's Health Across the Nation. J Gerontol A Biol Sci Med Sci. 2014 Aug;69(8):1011-7. doi: 10.1093/gerona/glt285. Epub 2014 Jan 24.
citation: Jones CM, Boelaert K. The Endocrinology of Ageing: A Mini-Review. Gerontology. 2015;61(4):291-300. doi: 10.1159/000367692. Epub 2014 Nov 27.
citation: Blumel JE, Lavin P, Vallejo MS, Sarra S. Menopause or climacteric, just a semantic discussion or has it clinical implications? Climacteric. 2014 Jun;17(3):235-41. doi: 10.3109/13697137.2013.838948. Epub 2013 Nov 7.
citation: Monteleone P, Mascagni G, Giannini A, Genazzani AR, Simoncini T. Symptoms of menopause - global prevalence, physiology and implications. Nat Rev Endocrinol. 2018 Apr;14(4):199-215. doi: 10.1038/nrendo.2017.180. Epub 2018 Feb 2.
citation: Kim MJ, Yim G, Park HY. Vasomotor and physical menopausal symptoms are associated with sleep quality. PLoS One. 2018 Feb 20;13(2):e0192934. doi: 10.1371/journal.pone.0192934. eCollection 2018.
citation: Sarrel P, Portman D, Lefebvre P, Lafeuille MH, Grittner AM, Fortier J, Gravel J, Duh MS, Aupperle PM. Incremental direct and indirect costs of untreated vasomotor symptoms. Menopause. 2015 Mar;22(3):260-6. doi: 10.1097/GME.0000000000000320.
citation: Avis NE, Crawford SL, Green R. Vasomotor Symptoms Across the Menopause Transition: Differences Among Women. Obstet Gynecol Clin North Am. 2018 Dec;45(4):629-640. doi: 10.1016/j.ogc.2018.07.005. Epub 2018 Oct 25.
citation: Langer RD, Hodis HN, Lobo RA, Allison MA. Hormone replacement therapy - where are we now? Climacteric. 2021 Feb;24(1):3-10. doi: 10.1080/13697137.2020.1851183. Epub 2021 Jan 6.
citation: Deecher DC, Dorries K. Understanding the pathophysiology of vasomotor symptoms (hot flushes and night sweats) that occur in perimenopause, menopause, and postmenopause life stages. Arch Womens Ment Health. 2007;10(6):247-57. doi: 10.1007/s00737-007-0209-5. Epub 2007 Dec 12.
citation: De Franciscis P, Cobellis L, Fornaro F, Sepe E, Torella M, Colacurci N. Low-dose hormone therapy in the perimenopause. Int J Gynaecol Obstet. 2007 Aug;98(2):138-42. doi: 10.1016/j.ijgo.2007.04.008. Epub 2007 Jun 18.
citation: Stubbs C, Mattingly L, Crawford SA, Wickersham EA, Brockhaus JL, McCarthy LH. Do SSRIs and SNRIs reduce the frequency and/or severity of hot flashes in menopausal women. J Okla State Med Assoc. 2017 May;110(5):272-274.
citation: Kapoor E, Faubion S, Hurt RT, Fischer K, Schroeder D, Fokken S, Croghan IT. A selective serotonin receptor agonist for weight loss and management of menopausal vasomotor symptoms in overweight midlife women: a pilot study. Menopause. 2020 Nov;27(11):1228-1235. doi: 10.1097/GME.0000000000001599.
citation: Ensrud KE, Joffe H, Guthrie KA, Larson JC, Reed SD, Newton KM, Sternfeld B, Lacroix AZ, Landis CA, Woods NF, Freeman EW. Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes: a randomized controlled trial. Menopause. 2012 Aug;19(8):848-55. doi: 10.1097/gme.0b013e3182476099.
citation: Wroolie TE, Williams KE, Keller J, Zappert LN, Shelton SD, Kenna HA, Reynolds MF, Rasgon NL. Mood and neuropsychological changes in women with midlife depression treated with escitalopram. J Clin Psychopharmacol. 2006 Aug;26(4):361-6. doi: 10.1097/01.jcp.0000227699.26375.f8.
citation: Shams T, Firwana B, Habib F, Alshahrani A, Alnouh B, Murad MH, Ferwana M. SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials. J Gen Intern Med. 2014 Jan;29(1):204-13. doi: 10.1007/s11606-013-2535-9. Epub 2013 Jul 26.
citation: Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, Cohen LS. Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life. Menopause. 2006 Sep-Oct;13(5):780-6. doi: 10.1097/01.gme.0000240633.46300.fa.
citation: Suvanto-Luukkonen E, Koivunen R, Sundstrom H, Bloigu R, Karjalainen E, Haiva-Mallinen L, Tapanainen JS. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopause. 2005 Jan-Feb;12(1):18-26. doi: 10.1097/00042192-200512010-00006.
citation: Barton DL, LaVasseur BI, Sloan JA, Stawis AN, Flynn KA, Dyar M, Johnson DB, Atherton PJ, Diekmann B, Loprinzi CL. Phase III, placebo-controlled trial of three doses of citalopram for the treatment of hot flashes: NCCTG trial N05C9. J Clin Oncol. 2010 Jul 10;28(20):3278-83. doi: 10.1200/JCO.2009.26.6379. Epub 2010 May 24.
citation: Soares CN, Poitras JR, Prouty J, Alexander AB, Shifren JL, Cohen LS. Efficacy of citalopram as a monotherapy or as an adjunctive treatment to estrogen therapy for perimenopausal and postmenopausal women with depression and vasomotor symptoms. J Clin Psychiatry. 2003 Apr;64(4):473-9. doi: 10.4088/jcp.v64n0419.
citation: Rathnayake N, Lenora J, Alwis G, Lekamwasam S. Cross cultural adaptation and analysis of psychometric properties of Sinhala version of Menopause Rating Scale. Health Qual Life Outcomes. 2018 Aug 6;16(1):161. doi: 10.1186/s12955-018-0977-9.
citation: Jahangiry L, Parviz R, Mirghafourvand M, Khazaee-Pool M, Ponnet K. The psychometric properties of the Persian menopause rating scale. BMC Womens Health. 2020 Aug 12;20(1):172. doi: 10.1186/s12905-020-01027-0.
citation: Ajani K, Nimavat D, Vidja M, Moradiya A, Panchasara D, Bhalodiya S, Miyatra K, Tank KD. Translation, Reliability, and Validity Test of Gujarati Version of Menopause Rating Scale in Postmenopausal Women for Menopause-Related Symptoms. Indian J Community Med. 2021 Jan-Mar;46(1):40-44. doi: 10.4103/ijcm.IJCM_163_20. Epub 2021 Mar 1.
citation: Anagnostis P, Bitzer J, Cano A, Ceausu I, Chedraui P, Durmusoglu F, Erkkola R, Goulis DG, Hirschberg AL, Kiesel L, Lopes P, Pines A, van Trotsenburg M, Lambrinoudaki I, Rees M. Menopause symptom management in women with dyslipidemias: An EMAS clinical guide. Maturitas. 2020 May;135:82-88. doi: 10.1016/j.maturitas.2020.03.007. Epub 2020 Mar 16.
citation: Guthrie KA, Larson JC, Ensrud KE, Anderson GL, Carpenter JS, Freeman EW, Joffe H, LaCroix AZ, Manson JE, Morin CM, Newton KM, Otte J, Reed SD, McCurry SM. Effects of Pharmacologic and Nonpharmacologic Interventions on Insomnia Symptoms and Self-reported Sleep Quality in Women With Hot Flashes: A Pooled Analysis of Individual Participant Data From Four MsFLASH Trials. Sleep. 2018 Jan 1;41(1):zsx190. doi: 10.1093/sleep/zsx190.
citation: Belso N, Kiss K, Rihmer Z, Tuzko N, Toth SJ, Paulin F. Major depressive disorder and response to citalopram treatment in women attending menopause clinic. Int J Psychiatry Clin Pract. 2003;7(4):269-72. doi: 10.1080/13651500310003183.
citation: Freeman MP, Hill R, Brumbach BH. Escitalopram for perimenopausal depression: an open-label pilot study. J Womens Health (Larchmt). 2006 Sep;15(7):857-61. doi: 10.1089/jwh.2006.15.857.
citation: Soares CN, Thase ME, Clayton A, Guico-Pabia CJ, Focht K, Jiang Q, Kornstein SG, Ninan P, Kane CP, Cohen LS. Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder. Menopause. 2010 Jul;17(4):700-11. doi: 10.1097/gme.0b013e3181d88962.
citation: Barton DL, Loprinzi CL, Novotny P, Shanafelt T, Sloan J, Wahner-Roedler D, Rummans TA, Christensen B, Dakhill SR, Martin LS. Pilot evaluation of citalopram for the relief of hot flashes. J Support Oncol. 2003 May-Jun;1(1):47-51.
citation: Defronzo Dobkin R, Menza M, Allen LA, Marin H, Bienfait KL, Tiu J, Howarth J. Escitalopram reduces hot flashes in nondepressed menopausal women: A pilot study. Ann Clin Psychiatry. 2009 Apr-Jun;21(2):70-6.
citation: Freedman RR, Kruger ML, Tancer ME. Escitalopram treatment of menopausal hot flashes. Menopause. 2011 Aug;18(8):893-6. doi: 10.1097/gme.0b013e31820ccae9.
citation: LaCroix AZ, Freeman EW, Larson J, Carpenter JS, Joffe H, Reed SD, Newton KM, Seguin RA, Sternfeld B, Cohen L, Ensrud KE. Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: a randomized controlled trial. Maturitas. 2012 Dec;73(4):361-8. doi: 10.1016/j.maturitas.2012.09.006. Epub 2012 Sep 30.
citation: Carpenter JS, Guthrie KA, Larson JC, Freeman EW, Joffe H, Reed SD, Ensrud KE, LaCroix AZ. Effect of escitalopram on hot flash interference: a randomized, controlled trial. Fertil Steril. 2012 Jun;97(6):1399-404.e1. doi: 10.1016/j.fertnstert.2012.03.001. Epub 2012 Apr 3.
citation: Joffe H, Guthrie KA, Larson J, Cohen LS, Carpenter JS, Lacroix AZ, Freeman EW. Relapse of vasomotor symptoms after discontinuation of the selective serotonin reuptake inhibitor escitalopram: results from the menopause strategies: finding lasting answers for symptoms and health research network. Menopause. 2013 Mar;20(3):261-8. doi: 10.1097/GME.0b013e31826d3108.
citation: Diem SJ, LaCroix AZ, Reed SD, Larson JC, Newton KM, Ensrud KE, Woods NF, Guthrie KA. Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials. Menopause. 2020 Oct;27(10):1126-1136. doi: 10.1097/GME.0000000000001597.
citation: Freeman EW, Guthrie KA, Caan B, Sternfeld B, Cohen LS, Joffe H, Carpenter JS, Anderson GL, Larson JC, Ensrud KE, Reed SD, Newton KM, Sherman S, Sammel MD, LaCroix AZ. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011 Jan 19;305(3):267-74. doi: 10.1001/jama.2010.2016.
citation: Davari-Tanha F, Soleymani-Farsani M, Asadi M, Shariat M, Shirazi M, Hadizadeh H. Comparison of citalopram and venlafaxine's role in treating sleep disturbances in menopausal women, a randomized, double-blind, placebo-controlled trial. Arch Gynecol Obstet. 2016 May;293(5):1007-13. doi: 10.1007/s00404-015-3900-1. Epub 2015 Oct 5.
citation: Shirazi M, Jalalian MN, Abed M, Ghaemi M. The Effectiveness of Melissa Officinalis L. versus Citalopram on Quality of Life of Menopausal Women with Sleep Disorder: A Randomized Double-Blind Clinical Trial. Rev Bras Ginecol Obstet. 2021 Feb;43(2):126-130. doi: 10.1055/s-0040-1721857. Epub 2021 Jan 19.
citation: Molaie M, Darvishi B, Jafari Azar Z, Shirazi M, Amin G, Afshar S. Effects of a combination of Nigella sativa and Vitex agnus-castus with citalopram on healthy menopausal women with hot flashes: results from a subpopulation analysis. Gynecol Endocrinol. 2019 Jan;35(1):58-61. doi: 10.1080/09513590.2018.1499086. Epub 2018 Aug 21.
citation: Valdes-Sustaita B, Lopez-Rubalcava C, Gonzalez-Trujano ME, Garcia-Viguera C, Estrada-Camarena E. Aqueous Extract of Pomegranate Alone or in Combination with Citalopram Produces Antidepressant-Like Effects in an Animal Model of Menopause: Participation of Estrogen Receptors. Int J Mol Sci. 2017 Dec 19;18(12):2643. doi: 10.3390/ijms18122643.
citation: Zhou J, Wang X, Feng L, Xiao L, Yang R, Zhu X, Shi H, Hu Y, Chen R, Boyce P, Wang G. Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study. BMC Psychiatry. 2021 May 19;21(1):260. doi: 10.1186/s12888-021-03253-8.
citation: Rios-Espinosa A, Cruz-Luna M, Garmendia-Gallardo C, Hernandez-Castanon MY, Hernandez-Hernandez VY, Sanchez-Tinoco PM, Bajonero-Dominguez A, Vergara Lope-Nunez JA, Alvarez-Perez MA, Gonzalez-Quiroz JL, Loranca-Moreno P, Ocampo-Godinez JM. Citalopram improves vasomotor syndrome and urogenital syndrome of menopause in Mexican women: a randomized clinical trial. Arch Gynecol Obstet. 2022 Dec;306(6):2035-2045. doi: 10.1007/s00404-022-06732-9. Epub 2022 Aug 23.