Comparison of Fluoxetine Versus Citalopram Therapy to Control Postmenopausal Vasomotor Syndrome

Hot Flashes Clinical Trial

Official title:

Citalopram Improves Vasomotor and Urogenital Syndromes in Mexican Patients With Post-menopause

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05346445
• Other study ID #: 122.2021
• Status: Completed
• Phase: N/A
• Start date: January 20, 2021
• Est. completion date: December 20, 2021

Study information

• Verified date: July 2022
• Source: Hospital Regional 1o de Octubre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: December 20, 2021
• Est. primary completion date: November 20, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Hot Flashes
• Postmenopause
• Syndrome

Intervention

Drug:
• Fluoxetine 20 MG
Participants received non-hormonal treatment with fluoxetine.
• Citalopram 20mg
Participants received non-hormonal treatment with citalopram.

Locations

Country	Name	City	State
Mexico	Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE	Mexico City

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Regional 1o de Octubre	National Polytechnic Institute, Mexico, Universidad Nacional Autonoma de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (40)

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. — View 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. Review. — View 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. Review. — View 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. — View 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. — View Citation

Belso N, Kiss K, Rihmer Z, Tüzko N, Tóth 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. — View Citation

Blümel JE, Lavín P, Vallejo MS, Sarrá 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. Review. — View 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. — View 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. — View 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. Epub 2007 Jun 18. — View 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. Epub 2007 Dec 12. Review. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum in: J Womens Health (Larchmt). 2006 Oct;15(8):988. — View 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). doi: 10.1093/sleep/zsx190. — View 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. — View 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. — View 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. Review. — View 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. Erratum in: Menopause. 2021 Feb 1;28(2):229. — View 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. — View 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. — View 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. Review. — View 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. — View 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. Review. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

Suvanto-Luukkonen E, Koivunen R, Sundström H, Bloigu R, Karjalainen E, Häivä-Mällinen 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. — View Citation

Valdés-Sustaita B, López-Rubalcava C, González-Trujano ME, García-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). pii: E2643. doi: 10.3390/ijms18122643. — View 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. — View 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. — View Citation

* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline Menopause Rating Scale (MRS) total score at 3 months	Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. It considers the score of the somatic, urogenital, and psychological domains. A score of 0-4 was considered minimal severity, 5-8 mild, 9-16 moderate, and greater than 17 severe.	3 months
Primary	Change from baseline Menopause Rating Scale (MRS) total score at 6 months	Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. It considers the score of the somatic, urogenital, and psychological domains. A score of 0-4 was considered minimal severity, 5-8 mild, 9-16 moderate, and greater than 17 severe.	6 months
Primary	Change from baseline Menopause Rating Scale (MRS) somatic domain score at 3 months	It considers the score obtained from the somatic dimension, which includes hot flashes, heart problems, sleep problems, and muscle and joint pain. A score of 0-2 was considered minimal severity, 3-4 mild, 5-8 moderate, and greater than 9 severe.	3 months
Primary	Change from baseline Menopause Rating Scale (MRS) somatic domain score at 6 months	It considers the score obtained from the somatic dimension, which includes hot flashes, heart problems, sleep problems, and muscle and joint pain. A score of 0-2 was considered minimal severity, 3-4 mild, 5-8 moderate, and greater than 9 severe.	6 months
Primary	Change from baseline Menopause Rating Scale (MRS) urogenital domain score at 3 months	It considers the score obtained from the urogenital dimension, which includes sexual problems, bladder problems and vaginal dryness. A score of 0 was considered minimal severity, 1 mild, 2-3 moderate, and greater than 4 severe.	3 months
Primary	Change from baseline Menopause Rating Scale (MRS) urogenital domain score at 6 months	It considers the score obtained from the urogenital dimension, which includes sexual problems, bladder problems and vaginal dryness. A score of 0 was considered minimal severity, 1 mild, 2-3 moderate, and greater than 4 severe.	6 months
Primary	Change from baseline Menopause Rating Scale (MRS) psychological domain score at 3 months	It considers the score obtained from the psychological dimension, which includes depression, irritability, anxiety and tiredness. A score of 0-1 was considered minimal severity, 2-3 mild, 4-6 moderate, and greater than 7 severe.	3 months
Primary	Change from baseline Menopause Rating Scale (MRS) psychological domain score at 6 months	It considers the score obtained from the psychological dimension, which includes depression, irritability, anxiety and tiredness. A score of 0-1 was considered minimal severity, 2-3 mild, 4-6 moderate, and greater than 7 severe.	6 months
Primary	Change from baseline score in Item 1 of the Menopause Rating Scale (MRS) at 3 months	Item 1 considers the score obtained from hot flashes on the MRS scale. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms.	3 months
Primary	Change from baseline score in Item 1 of the Menopause Rating Scale (MRS) at 6 months	Item 1 considers the score obtained from hot flashes on the MRS scale. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms.	3 months
Secondary	Change from the severity of individual Menopause Rating Scale (MRS) items at 6 months	It considers the obtained score from individual MRS items. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms.	6 months