Comparing the analgesic effect of fluoxetine plus vitamin e with vitamin e alone on mastodynia due to fibrocystic breast disease: a randomized double-blind clinical trial

Abstract

Mastodynia is a common symptom in women with fibrocystic breast disease and can substantially impair quality of life. Although vitamin E is frequently used for symptom relief, the potential additional analgesic effect of fluoxetine remains unclear. This study aimed to compare the analgesic effect of fluoxetine plus vitamin E with that of vitamin E plus placebo in women with mastodynia associated with fibrocystic breast disease. This double-blind, randomized clinical trial enrolled 78 women with mastodynia associated with fibrocystic breast disease who attended clinics affiliated with Shahrekord University of Medical Sciences, Shahrekord, Iran. Participants were randomly assigned (1:1) to receive either vitamin E (400 IU/day) plus fluoxetine (10 mg/day) or vitamin E (400 IU/day) plus placebo for 8 weeks. Randomization was computer-generated, allocation was concealed using identical medication packaging, and participants, investigators, and outcome assessors were blinded to treatment allocation. The primary outcome was breast pain intensity, assessed using the Visual Analog Scale (VAS) at baseline and at 1 and 2 months after treatment initiation. Secondary outcomes included breast heaviness, breast itching, and adverse events. Data were analyzed using repeated-measures analysis of variance and appropriate categorical tests. Seventy participants (35 per group) completed the study and were included in the analysis. Baseline demographic and clinical characteristics were comparable between the two groups. Repeated-measures analysis of variance demonstrated significant effects of treatment group (F (1,68) = 11.056, P = 0.001), time (F (2,136) = 164.321, P < 0.001), and the group-by-time interaction (F (2,136) = 60.996, P < 0.001) on breast pain intensity. No significant between-group differences were observed at baseline or after 1 month of treatment; however, after 2 months, breast pain intensity was significantly lower in the fluoxetine plus vitamin E group than in the vitamin E plus placebo group ( P < 0.001). Breast heaviness was also significantly less frequent in the combination therapy group after 1 month ( P = 0.009). Three participants in the fluoxetine group discontinued treatment because of adverse events, and no serious adverse events were reported in either group. The addition of fluoxetine to vitamin E improved breast pain after 8 weeks compared with vitamin E plus placebo in women with mastodynia associated with fibrocystic breast disease. These findings suggest that fluoxetine may be a useful adjunctive treatment; however, larger multicenter randomized trials with longer follow-up are needed to confirm its efficacy and safety. Iranian Registry of Clinical Trials (IRCT20200205046381N1), registered on February 28, 2020.