Short-Term Effects of Flupentixol-Melitracen on Regional Brain Function in Patients with Irritable Bowel Syndrome: An fMRI Study

Abstract

Background: The efficacy of the treatment for irritable bowel syndrome (IBS) with the combination of anxiolytic/antidepressant has been confirmed by clinical studies, but the central mechanism is unclear. Objectives: To investigate the effects of flupentixol-melitracen, a mixture of tricyclic antidepressant and a classical antipsychotic component, on resting-state brain function in IBS patients by using functional magnetic resonance imaging (fMRI). Patients and Methods: Thirty-two patients with IBS were randomly divided into an observation group (OG, n = 16) and control group (CG, n = 16). All patients in both groups were given spasmolytic agent (pinaverium bromide). For the OG group, flupentixol-melitracen was added. FMRI scans were performed in all patients before and four weeks after the therapy. The scores of gastrointestinal symptom rating scale (GSRS), Hamilton depression scale (HAMD-17) and anxiety scale (HAMA-14) were evaluated at the same time. FMRI regional homogeneity (ReHo) parameters were compared between the two groups before and after treatment using a 2 (therapy) × 2 (time) mixed model analysis of variance (ANOVA) statistical method, and were correlated with the changes of GSRS, HAMD and HAMA scores in the two groups. Results: The fMRI results of the mixed-model analysis of covariance (ANCOVA) and post analyses were as follows. When the therapeutic factor was the main effect, ReHo was increased in the left superior and middle occipital gyrus, and the left parietal gyrus, and decreased in the left thalamus and the lenticular nucleus in both groups after treatment when compared to the unmedicated state. In addition, the OG group showed decreased ReHo in the left superior temporal gyrus, the right lenticular-putamen nucleus, the right inferior frontal gyrus, the right insula, the right gyrus rectus and subcallosal gyrus. The CG group showed increased ReHo in the right angular gyrus. When the interaction between therapy and time was the main effect, the brain region with different ReHo values was in the left precuneus. In the OG group, the change of ReHo in the left precuneus was negatively correlated with the decrease of HAMD and HAMA scores. Conclusion: Flupentixol-melitracen can effectively improve anxiety, depression and gastrointestinal symptoms in patients with IBS, which may be related to the reversal of abnormal neural activity in the brain regions within the default network and the prefrontal-limbic-temporal emotional circuit in IBS patients.