| Objectives: Around a third of gastroesophageal reflux disease(GERD)patients treated with proton pump inhibitor(PPI)could not get a satisfying effect.In recent years,a new subsets of NERD called esophageal hypersensitivity was identified,and pain modulators(mostly antidepressants)may be effective for these patients.And GERD patients were more easily comorbid with anxiety and/or depression.There was some RCT researches about the effect of antidepressant on GERD,but the conclusion is inconsistent.So our research is to evaluate the efficacy and safety of antidepressants in the treatment of GERD through Meta-analysis and systematic review.Methods: We performed a systematic search of most of the database online up to January 2017 for including randomized controlled trials(RCTs)of antidepressants compared to placebo or other drugs in the treatment of GERD patients.Modified Jadad method was used to assess quality of all selected articles,and random effect model or fixed effect model was chosen to calculate effect variable according to the value of I2 in the heterogeneity test.Those data which cannot be quantificationally synthesized were made a descriptive analysis.Meta-analysis was performed by Rev Man 5.3 software to analyze the total effective rate of clinical symptoms,the effective rate of each symptoms(sour regurgitation,heartburn,chest pain),depression and anxiety scores after treatment,drop-out and lost to follow-up rate and the incidence of adverse events.Results: Nineteen RCTs,including eighteen full texts and one abstract,with 1443 cases totally(661 males and 782 females)were included in this review.Four articles were about antidepressants compared with placebo,five articles about antidepressants compared with PPI,two articles about antidepressants compared with anxiolytics,one article about two kinds of antidepressants compared with each other,and one article compared with prokinetics,and another one with Chinese medicine.(1)The results of quantitative analysis: the total effective rate of antidepressants(79.44%)on improving GERD symptoms was more than that of placebo(35.53%)[RR = 2.29,95% CI(1.19 ~ 4.42),p = 0.01].However,the effective rates had no significant difference between antidepressants and other drugs(PPI,anxiolytics,itopride,and Chinese medicine Xiang Sha Yang Wei pills).There was also no significan differentce in the effective rate between flupentixol and melitracen and paroxetine.In terms of the improvement of heartburn,antidepressants had an advantages compared with other drugs(including placebo and diazepam)[OR = 2.02,95% CI(1.09 ~ 3.72),p = 0.02].In terms of the improvement of chest pain,antidepressants had an advantages compared with diazepam[RR = 1.46,95% CI(1.18 ~ 1.81),p = 0.0005].However,in respect of the improvement of sour regurgitation,antidepressants had not any obvious advantage compared with other drugs(including placebo and diazepam)[RR = 1.25,95% CI(0.88 ~ 1.77),p=0.22].(2)Descriptive analysis results: The GERD patients taking fluoxetine(median 35.7,IQR 21.4-35.7)had higher percentage of hearburn-free days compared with either placebo(median 7.14,IQR 0-33.6,p < 0.001)or omeprazole(median 7.14,IQR 0-50,p < 0.001).The depression score was lower significantly in patients with treatment of flupenthixol and melitracen than with other drugs [SMD = 1.31,95% CI(1.93 ~ 0.69),p < 0.0001],while the anxiety score had no obviously decrease [SMD = 0.76,95% CI(1.98 ~ 1.98),p = 0.22].The drop-out rate and the incidence of adverse events were similar in patients taking either antidepressants or other drugs[RR= 0.47,95% CI(0.19 ~ 1.15),p = 0.10;RR = 0.89,95% CI(0.60 ~ 1.32),p = 0.57].Conclusions: The results suggested that antidepressants significantly improve the general symptoms,heartburn,chest pain,and depressive state in GERD patients,and the tolerance of antidepressants is good. |
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