Systematic review and network meta‐analysis: efficacy of drugs for functional dyspepsia

Abstract

Summary Background Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown. Aim To perform a systematic review with network meta‐analysis to resolve this uncertainty. Methods We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. Results We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58‐0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36‐0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo. Conclusions TCAs, histamine‐2 receptor antagonists, standard‐ and low‐dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.

Derivation and validation of a novel method to subgroup patients with functional dyspepsia: beyond upper gastrointestinal symptoms

“…Although psychological therapies are considered in guidelines for the management of functional dyspepsia, 46 especially for patients who are still symptomatic despite drug treatments, they remain an understudied area. Previous meta‐analyses have supported a potential causal role of psychological factors in functional gastrointestinal disorders, and that gastrointestinal symptoms, psychological distress, and impairments in quality of life can be alleviated with psychological therapies such as cognitive behavioural therapy, hypnotherapy, or gut‐brain neuromodulators, such as tricyclic antidepressants 8,21,46 . Antidepressants have been used in the treatment of functional dyspepsia to reduce anxiety and depression, to induce analgesia, and to improve sleep quality 47 .…”

“…One of the aims of this classification system was to direct therapy based on underlying pathophysiology. However, there is limited evidence that the evolving definitions of functional dyspepsia have improved clinical care or defined a particular group of patients with a different prognosis or different response to treatment 8 . In addition, these subgroups do not consider extraintestinal manifestations, or psychological factors and traits, which are considered integral to the pathophysiology of disorders of gut‐brain interaction.…”

Editorial: will clusters for anxiety, depression, sleep disturbance and fatigue symptoms predict treatment outcomes in functional dyspepsia? Authors' reply

“…As Van Zanten suggests, subgrouping patients with FD into clusters based on psychological and extra‐intestinal symptoms, as well as gastrointestinal symptoms, might be helpful to predict treatment success with tricyclic antidepressants (TCAs) or psychological therapies. In fact, as shown in our recent network meta‐analysis assessing relative efficacy of drugs for adults with FD, 7 TCAs were one of the most efficacious drugs, even in those whose symptoms were refractory to other drugs. This suggests that earlier use of TCAs may be beneficial.…”

Editorial: will clusters for anxiety, depression, sleep disturbance and fatigue symptoms predict treatment outcomes in functional dyspepsia?

“…Cure of Helicobacter pylori infection leads to symptom improvement in some FD patients, but most will have ongoing dyspepsia 1,4 . PPIs are effective in a sub‐group of FD patients 4‐6 …”

“…Antidepressants may be effective because of their stabilising effect on mood (and associated GI symptoms) but also by altering the stomach (gut)‐brain axis, ameliorating the perception of painful or unpleasant stimuli. Data are based on 5 RCTs comprising 228 patients 6,7 …”