Citalopram Vs Amitriptyline For The Treatment Of Irritable Bowel Syndrome:an8-week Follow Up, Open-label, Randomized Controlled Study

ObjectiveTherapy of the irritable bowel syndrome (IBS) will be still a challenge. Tricyclic antidepressant amitriptyline has good efficacy in IBS, but its clinical use is limited by consideration of tolerability. Citalopram, another antidepressant, acts as a selective serotonin reuptake inhibitor, may has a better tolerability. We compared Citalopram with amitriptyline for the treatment of patients with moderate IBS.MethodsSixty eight patients were enrolled in this randomized, open-label, non-inferiority,8-week clinical study. Subjects diagnosed based on Rome-3criteria received either Citalopram treatment (20-30mg/d, n=34) or amitriptyline treatment (75mg/d, n=34). Baseline characteristics and disease-related information were comparable. A10cm visual analogue scale was used to assess and compare the severity of global symptoms, abdominal pain, bloating and stool pattern at week4after treatment and at the endpoint respectively. Depressive and anxiety symptoms were assessed using the Hamilton rating scale for depression (HAMD) and Hamilton rating scale for anxiety (HAMA). The adverse events were recorded using the treatment emergent symptom scale. The primary efficacy was the relief of IBS symptoms. The secondary efficacy was the change of quality of life (endpoint versus baseline) evaluated by Short Form36(SF-36). Student’s t-test, Chi-square test and a multiple regression model were constructed in the intent-to-treat analysis.ResultsA higher dropout rates were noted in the amitriptyline arms compared to Citalopram arms (26.5%at4weeks and35.3%at8weeks vs5.9%at4weeks and11.8%at8weeks, all P<0.05). Adverse events such as constipation were significantly lower in the Citalopram group than the amitriptyline group. At the end of4weeks, there was a significant difference in the relief of global symptom, abdominal pain, bloating and depression scores with Citalopram over amitriptyline (2.6±1.1vs1.5±0.5,2.7±1.3vs1.1±0.4,1.1±0.8vs0.2±0.1, P<0.01respectively). This group difference was markedly and persisted to week8between Citalopram group and amitriptyline group in the enhancement of overall symptom, abdominal pain, bloating (4.4±2.1vs2.3±1.6,4.6±2.6vs2.5±1.3,2.2±1.4vs0.4±0.2, P<0.01respectively). Although amitriptyline significantly increase the quality of life in bodily pain (BP), more widespread SF-36domains including social functioning (SF), role limitations-emotional (RE), role limitations-physical (RP), general health (GH) and vitality (VT) enhanced after Citalopram treatment as well as BP dimension. A group difference (P<0.05) was found in BP and RE as compared between two groups at the endpoint. In multivariate linear regression analysis, the change of IBS symptoms was primarily correlated with SF-36scores whereas the Hamilton rating scale for depression only had significant correlation with BP (β=0.55, P<0.05)and VT (β=0.87, P<0.01).ConclusionCitalopram is superior to amitriptyline in the treatment of IBS in terms of both efficacy and tolerability and its action may be through an independent mechanism on improving anxiety and depression.