The influence of fluoxetine on the blood pressure: a meta-analysis of randomized controlled trials

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.

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).

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 mmHg; 95% CI: 0.14 to 14.80; p = 0.046) and diastolic BP (DBP) (WMD: 4.19 mmHg; 95% CI: 0.44 to 7.93; p = 0.028); 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 mmHg; 95% CI: 1.53 to 19.80; p = 0.022) and DBP (WMD: 6.65 mmHg; 95% CI: 4.30 to 8.99; p < 0.001) were more pronounced in trials lasting 12 weeks or less. No significant changes in BP were observed in studies with longer durations.

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.