Immediate‐Term Dapoxetine Administration Suppressed Functional Connectivity of Subcallosal Cingulate Cortex in Premature Ejaculation: A Resting‐State fMRI Study

INTRODUCTION: Dapoxetine, a short-acting selective serotonin reuptake inhibitor (SSRI), is commonly prescribed to treat premature ejaculation (PE). Functional connectivity (FC) between dorsolateral prefrontal cortex (DLPFC) and subcallosal cingulate cortex (SCC) has been found to serve as neuroimaging biomarker for predicting SSRI treatment response. Despite the fact that altered FC has been observed in PE patients, the neural mechanisms underlying the rapid-acting effects on brain of immediate-term dapoxetine administration remain unknown. This study aimed to explore the mechanisms underlying this therapeutic effect based on DLPFC and SCC, which are involved in the regulation of ejaculatory reflex. METHODS: Resting-state functional magnetic resonance imaging and structural MRI data were acquired from a sample of 40 PE patients before and after immediate-term dapoxetine administration, as well as 40 healthy controls (HCs). Seed-based voxel-wise FC analysis was performed, and whole-brain FC values in regions of interest (ROIs) (bilateral SCC and DLPFC: spheres with 6 mm radius) were calculated. FC values of bilateral DLPFC and SCC were compared between PE patients before and after dapoxetine administration and HCs. RESULTS: Using SCC as ROIs, treatment-naïve PE patients showed decreased FC within the default mode network (p < 0.005) but increased FC with the attention network (p < 0.005) compared to HCs. Following dapoxetine administration, the pattern of alterations compared to HCs changed, now additionally featuring decreased FC between the SCC and the visual network (p < 0.005). Crucially, within-patient comparisons revealed that dapoxetine administration significantly decreased FC between the SCC and both the attention network (p < 0.005) and the visual network (p < 0.005). In contrast, using DLPFC as ROIs revealed widespread hypocomnectivity in patients, which remained unchanged following acute administration. CONCLUSION: The therapeutic effects of immediate-term dapoxetine administration may act by downregulating FC of SCC and related circuits (promotional factors for PE), but do not enhance FC of DLPFC and related circuits (inhibition factors for PE). The latter may be achieved by long-term dapoxetine administration or other long-acting SSRI treatments.