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BACKGROUND & AIMS
Although there have been multiple drugs tested in gastroparesis, their relative efficacy and safety is unknown. We evaluated this in a network meta-analysis of randomized controlled trials (RCTs).
We searched the literature to 7th September 2022. We judged drugs' efficacy based on global symptoms of gastroparesis, individual symptoms including nausea, vomiting, abdominal pain, bloating, or fullness, and safety according to total adverse events and adverse events leading to withdrawal. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of not improving with 95% confidence intervals (CIs), ranking drugs according to P-score.
We identified 29 RCTs (3772 patients). Based on global symptoms, clebopride ranked first for efficacy (RR = 0.30; 95% CI 0.16-0.57, P-score 0.99) followed by domperidone (RR = 0.69; 95% CI 0.48-0.98, P-score 0.76). No other drug was superior to placebo. Only two drug classes were efficacious: in rank order, oral dopamine antagonists (RR = 0.58; 95% CI 0.44-0.77, P-score 0.96) and tachykinin-1 antagonists (RR = 0.69; 95% CI 0.52-0.93, P-score 0.83). For individual symptoms, oral metoclopramide ranked first for nausea (RR 0.46; 95% CI 0.21-1.00, P-score 0.95), fullness (RR 0.67; 95% CI 0.35-1.28, P-score 0.86), and bloating (RR 0.53; 95% CI 0.30-0.93, P-score 0.97), based on only one small trial. Only prucalopride was more likely to be associated with adverse events than placebo.
In a network meta-analysis, oral dopamine antagonists and tachkinin-1 antagonists were more efficacious than placebo for gastroparesis, but confidence in the evidence was low to moderate for most comparisons. There is an unmet need for efficacious therapies for gastroparesis.
Disclosure statements are available on the authors' profiles:
Efficacy and Safety of Drugs for Gastroparesis: Systematic Review and Network Meta-analysisGastroenterology 2022 Dec 26;[EPub Ahead of Print], MR Ingrosso, M Camilleri, J Tack, G Ianiro, CJ Black, AC Ford
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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Drugs for gastroparesis
A systematic review with a network meta-analysis often suggests a large sample size. However, the fact that this one only included 29 randomized controlled trials with a total of 3772 patients confirms the authors' conclusions that the data in support of pharmaceuticals for gastroparesis is limited.
The class of drugs found to have the greatest benefit is dopamine antagonists. Clebopride and domperidone came out on top, but unfortunately, they are not available in the US. Domperidone is available in Canada and other countries but has a black-box warning in the US due to the associated risk of prolonged QT syndrome and extrapyramidal side effects. No other drugs were found to be better than placebo for global improvement in gastroparesis. The only drug approved by the FDA for gastroparesis is metoclopramide (also a dopamine antagonist). It was found to have the greatest benefit on fullness and bloating. Serotonin (5-HT4) agonists are also available including prucalopride. However, this review did not show a significant benefit over placebo with these drugs.
Therapeutic summary for gastroparesis
Prescribe for no longer than 3 months to reduce the risk of extrapyramidal side effects. Include 2-week holidays between dosing to reassess its efficacy and limit side effects.