{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T07:02:35Z","timestamp":1779951755537,"version":"3.53.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>There are ongoing controversies regarding the impact of fluoxetine on blood pressure (BP), and a comprehensive analysis specifically addressing this relationship is lacking. Given the limited detail in existing literature on BP fluctuations during fluoxetine treatment, we conducted this meta-analysis to evaluate BP variations, providing clinically relevant insights.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A structured and comprehensive review was conducted using systematic review and meta-analytic approaches. Only randomized controlled trials (RCTs) comparing fluoxetine with placebo were included. Exhaustive searches were performed across major scholarly databases, including Scopus, Web of Science, Embase, and PubMed\/MEDLINE, covering all records up to July 28, 2025. Pooled estimates were calculated using the DerSimonian and Laird random-effects model, and results were reported as weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five RCT arms encompassing a total of 538 participants were included in the current meta-analysis. Fluoxetine treatment was associated with a statistically significant increase in systolic BP (SBP) (WMD: 7.47\u2005mmHg; 95% CI: 0.14 to 14.80;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.046) and diastolic BP (DBP) (WMD: 4.19\u2005mmHg; 95% CI: 0.44 to 7.93;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.028); however, these findings should be interpreted cautiously due to substantial heterogeneity and the limited number of included studies. Subgroup analyses based on treatment duration indicated that increases in SBP (WMD: 10.66\u2005mmHg; 95% CI: 1.53 to 19.80;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022) and DBP (WMD: 6.65\u2005mmHg; 95% CI: 4.30 to 8.99;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) were more pronounced in trials lasting 12 weeks or less. No significant changes in BP were observed in studies with longer durations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While fluoxetine was associated with modest increases in SBP and DBP, these findings should not be interpreted as evidence supporting its clinical use for the management of hypotension or orthostatic hypotension. The included trials did not specifically enroll hypotensive populations, and the limited number of studies with substantial heterogeneity restricts the clinical applicability of this observation. Further clinical and experimental studies are warranted to better understand the relationship between fluoxetine and BP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1813209","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:17:33Z","timestamp":1779949053000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The influence of fluoxetine on the blood pressure: a meta-analysis of randomized controlled trials"],"prefix":"10.3389","volume":"13","author":[{"given":"Deyun","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, The First People\u2019s Hospital of Xiaoshan District","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The First People\u2019s Hospital of Xiaoshan District","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousalya","family":"Prabahar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk","place":["Tabuk, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Safargar","sequence":"additional","affiliation":[{"name":"Student Research Committee, Tabriz University of Medical Sciences","place":["Tabriz, Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41581-019-0244-2","article-title":"The global epidemiology of hypertension","volume":"16","author":"Mills","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/j.jacc.2018.07.008","article-title":"Prevention and control of hypertension: jACC health promotion series","volume":"72","author":"Carey","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"100755","DOI":"10.1016\/j.curtheres.2024.100755","article-title":"Impact of magnesium supplementation on blood pressure: an umbrella meta-analysis of randomized controlled trials","volume":"101","author":"Alharran","year":"2024","journal-title":"Curr Ther Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","article-title":"Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants","volume":"398","author":"Zhou","year":"2021","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1016\/S0140-6736(14)60685-1","article-title":"Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1\u00b7 25 million people","volume":"383","author":"Rapsomaniki","year":"2014","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"387","DOI":"10.3390\/neurolint13030038","article-title":"Selective serotonin reuptake inhibitors and adverse effects: a narrative review","volume":"13","author":"Edinoff","year":"2021","journal-title":"Neurol Int"},{"key":"B7","doi-asserted-by":"publisher","first-page":"316","DOI":"10.5498\/wjp.v11.i7.316","article-title":"Selective serotonin reuptake inhibitors and risk reduction for cardiovascular disease in patients with schizophrenia: a controversial but promising approach","volume":"11","author":"Bellon","year":"2021","journal-title":"World J Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"112040","DOI":"10.1016\/j.diabres.2025.112040","article-title":"The effect of Fluoxetine on lipid profiles in overweight or obese individuals: a systematic review and meta-analysis of randomized controlled trials","volume":"222","author":"Liu","year":"2025","journal-title":"Diabetes Res Clin Pract"},{"key":"B9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1097\/00004714-199902000-00004","article-title":"Blood pressure changes during short-term fluoxetine treatment","volume":"19","author":"Amsterdam","year":"1999","journal-title":"J Clin Psychopharmacol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"148","DOI":"10.4306\/pi.2013.10.2.148","article-title":"Relationship between SSRIs and metabolic syndrome abnormalities in patients with generalized anxiety disorder: a prospective study","volume":"10","author":"Beyazy\u00fcz","year":"2013","journal-title":"Psychiatry Investig"},{"key":"B11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.4103\/1735-1995.189647","article-title":"Selective serotonin reuptake inhibitors and cardiovascular events: a systematic review","volume":"21","author":"Nezafati","year":"2016","journal-title":"J Res Med Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.jash.2018.06.002","article-title":"The association between antidepressant use and orthostatic hypotension in older people: a matched cohort study","volume":"12","author":"Briggs","year":"2018","journal-title":"J Am Soc Hypertens"},{"key":"B13","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1097\/EDE.0000000000000840","article-title":"Depressive symptoms, antidepressant use, and hypertension in young adulthood","volume":"29","author":"Crookes","year":"2018","journal-title":"Epidemiology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1177\/00912700122009746","article-title":"Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure patients","volume":"41","author":"Graff","year":"2001","journal-title":"J Clin Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1093\/ptj\/89.9.873","article-title":"Reprint\u2014preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"89","author":"Moher","year":"2009","journal-title":"Phys Ther"},{"key":"B16","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"Br Med J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"Br Med J"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clineuro.2018.02.029","article-title":"Effect of fluoxetine on three-year recurrence in acute ischemic stroke: a randomized controlled clinical study","volume":"168","author":"He","year":"2018","journal-title":"Clin Neurol Neurosurg"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/ijo.2013.225","article-title":"A comparative study of five centrally acting drugs on the pharmacological treatment of obesity","volume":"38","author":"Suplicy","year":"2014","journal-title":"Int J Obes"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.2337\/db08-0236","article-title":"Effects of a selective serotonin reuptake inhibitor, fluoxetine, on counterregulatory responses to hypoglycemia in healthy individuals","volume":"57","author":"Briscoe","year":"2008","journal-title":"Diabetes"},{"key":"B21","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1002\/j.1550-8528.1994.tb00641.x","article-title":"No specific effect of fluoxetine treatment on fasting glucose, insulin, lipid levels, and blood pressure in healthy men with abdominal obesity","volume":"2","author":"Visser","year":"1994","journal-title":"Obes Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jad.2023.08.032","article-title":"A meta-analysis on the association between SSRIs and blood pressure in patients with CVD and depression","volume":"340","author":"Zhang","year":"2023","journal-title":"J Affect Disord"},{"key":"B23","doi-asserted-by":"publisher","first-page":"26","DOI":"10.4103\/2008-7802.174891","article-title":"Can antidepressant drug impact on blood pressure level in patients with psychiatric disorder and hypertension? A randomized trial","volume":"7","author":"Razavi Ratki","year":"2016","journal-title":"Int J Prev Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/jhh.2013.82","article-title":"Alcohol and psychotropic drugs: risk factors for orthostatic hypotension in elderly fallers","volume":"31","author":"Gaxatte","year":"2017","journal-title":"J Hum Hypertens"},{"key":"B25","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/fcp.12440","article-title":"Hypertension induced by serotonin reuptake inhibitors: analysis of two pharmacovigilance databases","volume":"33","author":"Humbert","year":"2019","journal-title":"Fundam Clin Pharmacol"},{"key":"B26","first-page":"gfaa142.P0150","article-title":"Effect of serotonin reuptake inhibitors (SSRIS) and serotonin-norepinephrine reuptake inhibitors (SNRIS) on blood pressure variability using 24 h ambulatory blood pressure monitoring","volume-title":"Nephrology Dialysis Transplantation","author":"Aslam","year":"2020"},{"key":"B27","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1111\/j.1472-8206.2000.tb00426.x","article-title":"Fluoxetine-induced pressor response in freely moving rats: a role for vasopressin and sympathetic tone","volume":"14","author":"Lazartigues","year":"2000","journal-title":"Fundam Clin Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3390\/biomedicines10010056","article-title":"Off-target effects of antidepressants on vascular function and structure","volume":"10","author":"Dimoula","year":"2021","journal-title":"Biomedicines"},{"key":"B29","doi-asserted-by":"publisher","first-page":"704281","DOI":"10.3389\/fcvm.2021.704281","article-title":"Antidepressant drugs effects on blood pressure","volume":"8","author":"Calvi","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ejphar.2017.02.029","article-title":"Chronic treatment with fluoxetine modulates vascular adrenergic responses by inhibition of pre-and post-synaptic mechanisms","volume":"800","author":"Pereira","year":"2017","journal-title":"Eur J Pharmacol"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1813209\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:17:34Z","timestamp":1779949054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1813209\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":30,"alternative-id":["10.3389\/fcvm.2026.1813209"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1813209","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]},"article-number":"1813209"}}