BackgroundMitral valve prolapse (MVP) is accompanied by mental disorders including anxiety, which has similar presentations as MVP. It is hypothesised that treatment of anxiety might reduce the symptoms of MVP.ObjectiveThe aim of this study was to assess the clinical and echocardiographic effects of fluoxetine administration in patients with MVP and anxiety.MethodsThis randomized clinical trial was conducted on patients with documented MVP and generalised anxiety disorder (GAD) who were referred to Mashhad University of Medical Sciences cardiology clinics, Mashhad, Iran in 2015. Subjects were randomly assigned to intervention group who received propranolol and fluoxetine (both at 10 mg/day) and control group who received 10 mg/day propranolol. Assessments included echocardiography and GAD-7 questionnaire and rating of chest pain, that were performed at baseline and then weekly for 4 weeks. Analysis was performed using the Mann-Whitney U test and Two-way Repeated Measures Analysis of Variance (ANOVA).ResultsSixty patients (25 male/ 35 female) with a mean age of 22.9 ± 2.5 years were studied in two groups of intervention (n = 30) and control (n = 30). GAD score was significantly higher in the intervention group (17.37 ± 1.61) compared with the control group (14.17 ± 0.83) (p<0.001). No significant difference was observed for changes in left atrium diameter, mitral annular diameter, left ventricular diameter or ejection fraction (p>0.05). Pain severity was reduced significantly more in control group (3.27 ± 1.26) compared to intervention group (2.80 ± 0.85) after treatment (p<0.001).ConclusionsThis study revealed that the co-administration of fluoxetine and propranolol may not only have no effective in improving echocardiographic changes of MVP but may also aggravate subjective findings of patients with MVP and GAD.Trial registrationThe trial is registered at the Iranian Clinical Trial Registry (IRCT.ir) with the IRCT identification number IRCT2014102819721N1.FundingThis research has been financially supported by Research Council of Sabzevar University of Medical Sciences.