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Open Access 01-12-2021 | Mood Disorders | Research article

Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study

Authors: Jingjing Zhou, Xiao Wang, Lei Feng, Le Xiao, Rui Yang, Xuequan Zhu, Hui Shi, Yongdong Hu, Runsen Chen, Philip Boyce, Gang Wang

Published in: BMC Psychiatry | Issue 1/2021

Abstract

Background

In the population of postmenopausal patients with major depressive disorder (MDD), the superiority of serotonin-norepinephrine reuptake inhibitors (SNRIs) over selective serotonin reuptake inhibitors (SSRIs) has not yet been definitively proven. Consequently, a direct comparison of the efficacy of SSRIs and SNRIs in the treatment of postmenopausal depression could provide relevant data. The aim of this study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of postmenopausal MDD.

Methods

This was an 8-week, multicenter, randomized, single-blind, active-controlled trial conducted at a psychiatric hospital (Beijing Anding Hospital) and a general hospital (Beijing Chaoyang Hospital) between April 2013 and September 2017. The primary outcome measure was improving depressive symptoms (Hamilton Depression Rating Scale (HAMD-24) score). The secondary outcomes included the change of HAMD-24 anxiety/somatization factor score and Clinical Global Impressions-Improvement (CGI-I) response rate. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory tests. Efficacy was analyzed by using the full analysis set (FAS) following the modified intention-to-treat (mITT) principle. The primary endpoint measurements were analyzed using a mixed-effect model for repeated measures (MMRM) model with patients as a random-effect factor, treatment group as the independent variable, time as a repeated measure, and baseline covariates, using a first-order ante dependence covariance matrix.

Results

A total of 184 women were randomized. The full analysis set (FAS) included 172 patients (venlafaxine, n = 82; fluoxetine, n = 90). Over the 8-week study period, the reduction in HAMD-24 scores was significant (P < 0.001) in both groups, while a significantly greater decline from baseline was observed in the venlafaxine group compared with the fluoxetine group (least-squares mean difference [95% CI]: − 2.22 [− 7.08, − 0.41]), P = 0.001). The baseline-to-week-8 least-squares mean change of the anxiety/somatization factor scores, CGI-I response rate were greater in the venlafaxine group than in the fluoxetine group (all P < 0.05). The most frequent TEAEs (≥5%) in both groups were nausea, somnolence, dizziness, headache, and dry mouth. There was no significant difference in the incidence of adverse events between the two groups.

Conclusion

Venlafaxine was well tolerated and compared to fluoxetine, it led to a greater improvement in the treatment of postmenopausal MDD.

Trial registration

Clinical Trials. gov #NCT01824433. The trial was registered on April 4, 2013.

National Collaborating Centre for Mental Health commissioned by the National Institute for Health and Care Excellence (NICE). Depression in adults: the treatment and management of depression in adults (updated edition). London: NICE; 2009.

Gelenberg AJ, Freeman MP, Markowitz JC. Practice guideline for the treatment of patients with major depressive disorder (third edition). Washington, D.C.: American Psychiatric Association; 2010.

Brody DJ, Pratt LA, Hughes JP. Prevalence of Depression Among Adults Aged 20 and Over: United States, 2013–2016. NCHS Data Brief: 1–8; 2018.

World Health Organization: Depression and Other Common Mental Disorders: Global Health Estimates. 2017.

Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T, et al. Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med. 2013;43(3):471–81. https://doi.org/10.1017/S0033291712001511.CrossRefPubMed

Unsal A, Tozun M, Ayranci U. Prevalence of depression among postmenopausal women and related characteristics. Climacteric. 2011;14(2):244–51. https://doi.org/10.3109/13697137.2010.510912.CrossRefPubMed

Jung SJ, Shin A, Kang D. Hormone-related factors and post-menopausal onset depression: results from KNHANES (2010-2012). J Affect Disord. 2015;175:176–83. https://doi.org/10.1016/j.jad.2014.12.061.CrossRefPubMed

Grigoriadis S, Bouffard BA, Kennedy S, Bagby RM, Joffe RT. A comparison of desipramine response in younger and older women. J Clin Psychopharmacol. 2010;30(1):80–2. https://doi.org/10.1097/JCP.0b013e3181c82717.CrossRefPubMed

Pinto-Meza A, Usall J, Serrano-Blanco A, Suarez D, Haro JM. Gender differences in response to antidepressant treatment prescribed in primary care. Does menopause make a difference? J Affect Disord. 2006;93(1–3):53–60. https://doi.org/10.1016/j.jad.2006.02.010.CrossRefPubMed

10.

Kornstein SG, Clayton AH, Soares CN, Padmanabhan SK, Guico-Pabia CJ. Analysis by age and sex of efficacy data from placebo-controlled trials of desvenlafaxine in outpatients with major depressive disorder. J Clin Psychopharmacol. 2010;30(3):294–9. https://doi.org/10.1097/JCP.0b013e3181dcb594.CrossRefPubMed

11.

Burt VK, Wohlreich MM, Mallinckrodt CH, Detke MJ, Watkin JG, Stewart DE. Duloxetine for the treatment of major depressive disorder in women ages 40 to 55 years. Psychosomatics. 2005;46(4):345–54. https://doi.org/10.1176/appi.psy.46.4.345.CrossRefPubMed

12.

Melichar JK, Haida A, Rhodes C, Reynolds AH, Nutt DJ, Malizia AL. Venlafaxine occupation at the noradrenaline reuptake site: in-vivo determination in healthy volunteers. J Psychopharmacol (Oxford, England). 2001;15(1):9–12.CrossRef

13.

Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. 2018;19(10):1057–70. https://doi.org/10.1080/14656566.2018.1491966.CrossRefPubMedPubMedCentral

14.

Ungvari Z, Tarantini S, Yabluchanskiy A, Csiszar A. Potential adverse cardiovascular effects of treatment with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) in patients with geriatric depression: implications for Atherogenesis and Cerebromicrovascular dysregulation. Front Genet. 2019;10:898. https://doi.org/10.3389/fgene.2019.00898.CrossRefPubMedPubMedCentral

15.

Hamilton M. Rating depressive patients. J Clin Psychiatr. 1980;41(12 Pt 2):21–4.

16.

Williams JB. A structured interview guide for the Hamilton depression rating scale. Arch Gen Psychiatr. 1988;45(8):742–7. https://doi.org/10.1001/archpsyc.1988.01800320058007.CrossRefPubMed

17.

Guy W. Clinical global impressions (CGI) scale, modified. In: Rush JA, Task force for the handbook of psychiatric measures, editors. Handbook of Psychiatric Measures (1st ed). Edn. Washington, D.C.: American Psychiatric Association; 2000.

18.

Dierick M, Ravizza L, Realini R, Martin A. A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog Neuro-Psychopharmacol Biol Psychiatry. 1996;20(1):57–71. https://doi.org/10.1016/0278-5846(95)00292-8.CrossRef

19.

Martenyi F, Dossenbach M, Mraz K, Metcalfe S. Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile. Eur Neuropsychopharmacol. 2001;11(3):227–32. https://doi.org/10.1016/S0924-977X(01)00089-X.CrossRefPubMed

20.

Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry. 2000;157(9):1445–52. https://doi.org/10.1176/appi.ajp.157.9.1445.CrossRefPubMed

21.

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;293(5):1007–13. https://doi.org/10.1007/s00404-015-3900-1.CrossRefPubMed

22.

Soares CN, Thase ME, Clayton A, Guico-Pabia CJ, Focht K, Jiang Q, et al. Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder. Menopause (New York, NY). 2010;17(4):700–11.CrossRef

23.

Haskins JT, Moyer JA, Muth EA, Sigg EB. DMI, Wy-45,030, Wy-45,881 and ciramadol inhibit locus coeruleus neuronal activity. Eur J Pharmacol. 1985;115(2–3):139–46. https://doi.org/10.1016/0014-2999(85)90684-3.CrossRefPubMed

24.

Wong DT, Bymaster FP, Engleman EA. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci. 1995;57(5):411–41. https://doi.org/10.1016/0024-3205(95)00209-O.CrossRefPubMed

25.

Almeida OP, Lautenschlager N, Vasikaram S, Leedman P, Flicker L. Association between physiological serum concentration of estrogen and the mental health of community-dwelling postmenopausal women age 70 years and over. Am J Geriatric Psychiatr. 2005;13(2):142–9. https://doi.org/10.1097/00019442-200502000-00008.CrossRef

26.

Morgan ML, Cook IA, Rapkin AJ, Leuchter AF. Estrogen augmentation of antidepressants in perimenopausal depression: a pilot study. J Clin Psychiatr. 2005;66(6):774–80. https://doi.org/10.4088/JCP.v66n0617.CrossRef

27.

Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB, Meyers BS. Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Fluoxetine collaborative study group. Am J Geriatric Psychiatr. 1997;5(2):97–106. https://doi.org/10.1097/00019442-199721520-00002.CrossRef

28.

Smith LJ, Henderson JA, Abell CW, Bethea CL. Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques. Neuropsychopharmacol. 2004;29(11):2035–45. https://doi.org/10.1038/sj.npp.1300510.CrossRef

29.

Holschneider DP, Kumazawa T, Chen K, Shih JC. Tissue-specific effects of estrogen on monoamine oxidase a and B in the rat. Life Sci. 1998;63(3):155–60. https://doi.org/10.1016/S0024-3205(98)00255-0.CrossRefPubMed

30.

Gundlah C, Alves SE, Clark JA, Pai LY, Schaeffer JM, Rohrer SP. Estrogen receptor-beta regulates tryptophan hydroxylase-1 expression in the murine midbrain raphe. Biol Psychiatry. 2005;57(8):938–42. https://doi.org/10.1016/j.biopsych.2005.01.014.CrossRefPubMed

31.

Sanchez RL, Reddy AP, Centeno ML, Henderson JA, Bethea CL. A second tryptophan hydroxylase isoform, TPH-2 mRNA, is increased by ovarian steroids in the raphe region of macaques. Brain Res Mol Brain Res. 2005;135(1–2):194–203. https://doi.org/10.1016/j.molbrainres.2004.12.011.CrossRefPubMed

32.

Sumner BE, Grant KE, Rosie R, Hegele-Hartung C, Fritzemeier KH, Fink G. Raloxifene blocks estradiol induction of the serotonin transporter and 5-hydroxytryptamine2A receptor in female rat brain. Neurosci Lett. 2007;417(1):95–9. https://doi.org/10.1016/j.neulet.2007.02.039.CrossRefPubMed

33.

De Nayer A, Geerts S, Ruelens L, Schittecatte M, De Bleeker E, Van Eeckhoutte I, et al. Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety. Int J Neuropsychopharmacol. 2002;5(2):115–20. https://doi.org/10.1017/S1461145702002857.CrossRefPubMed

34.

Feighner JP. Mechanism of action of antidepressant medications. J Clin Psychiatr. 1999;60(Suppl 4):4–11 discussion 12-13.

35.

Davidson JR, Meoni P, Haudiquet V, Cantillon M, Hackett D. Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms. Depression Anxiety. 2002;16(1):4–13. https://doi.org/10.1002/da.10045.CrossRefPubMed

36.

Bener A, Rizk DE, Shaheen H, Micallef R, Osman N, Dunn EV. Measurement-specific quality-of-life satisfaction during the menopause in an Arabian gulf country. Climacteric. 2000;3(1):43–9. https://doi.org/10.3109/13697130009167598.CrossRefPubMed

37.

Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, et al. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005;23(28):6931–40. https://doi.org/10.1200/JCO.2005.11.181.CrossRefPubMed

38.

Lutwak N, Dill C. A depressed post-menopausal woman. J Emergency Med. 2012;43(5):815–9. https://doi.org/10.1016/j.jemermed.2011.05.040.CrossRef

39.

Schuch JJ, Roest AM, Nolen WA, Penninx BW, de Jonge P. Gender differences in major depressive disorder: results from the Netherlands study of depression and anxiety. J Affect Disord. 2014;156:156–63. https://doi.org/10.1016/j.jad.2013.12.011.CrossRefPubMed

40.

Kim JH, Cho MJ, Hong JP, Bae JN, Cho SJ, Hahm BJ, et al. Gender differences in depressive symptom profile: Results from Nationwide general population surveys in Korea. J Korean Med Sci. 2015;30(11):1659–66. https://doi.org/10.3346/jkms.2015.30.11.1659.CrossRefPubMedPubMedCentral

41.

Kornstein SG, Young EA, Harvey AT, Wisniewski SR, Barkin JL, Thase ME, et al. The influence of menopause status and postmenopausal use of hormone therapy on presentation of major depression in women. Menopause (New York, NY). 2010;17(4):828–39.CrossRef

Title: Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study
Authors: Jingjing Zhou
Xiao Wang
Lei Feng
Le Xiao
Rui Yang
Xuequan Zhu
Hui Shi
Yongdong Hu
Runsen Chen
Philip Boyce
Gang Wang
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Mood Disorders
Affective Disorder
Fluoxetine
Venlafaxine
Published in: BMC Psychiatry / Issue 1/2021
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/s12888-021-03253-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study

Abstract

Background

Methods

Results

Conclusion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Trial registration

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