Gastroparesis, a rare motility disorder that affects gastric emptying, presents significant challenges in diagnosis and treatment. With limited therapeutic options and frequent misdiagnosis, patients often struggle to find effective care. Experts are now advocating for a reevaluation of the understanding of this complex condition, emphasizing the need for innovative treatment strategies.
The difficulties associated with gastroparesis stem from its diverse symptoms and the lack of effective diagnostic protocols. According to Brian Lacy, MD, PhD, from the Mayo Clinic, the field of gastroparesis is characterized by three key attributes: challenging, complicated, and controversial. Misdiagnosis is common, often exacerbated by inadequately performed tests.
In 2022, the American Gastroenterological Association (AGA) released comprehensive guidelines aimed at improving the diagnosis and treatment of gastroparesis. The AGA recommends scintigraphic gastric emptying of a solid meal lasting at least three hours as the primary diagnostic tool, cautioning against shorter studies due to the risk of false negatives.
Despite these guidelines, Douglas Weinstein, MD, director of GI Motility at Hackensack Meridian Jersey Shore University Medical Center, highlights that numerous factors, including the composition of the test meal and the patient’s position during the test, can affect results. He states, “Even if everything’s done right, sometimes [the test] will still be normal.”
Compounding the issue, the AGA guidelines primarily endorse treatments that are not yet substantiated for use in gastroparesis. The only FDA-approved treatment remains metoclopramide, a dopamine receptor antagonist first approved in 1979 for diabetic gastroparesis. In 2020, the FDA approved Evoke Pharma’s nasal spray formulation of metoclopramide, known as Gimoti, marking a rare advancement in treatment options.
Despite this progress, concerns about metoclopramide persist. Its use is limited to short durations, and it carries significant side effects, including the risk of tardive dyskinesia. Weinstein points out, “Metoclopramide is not a good medicine because it can’t be used long-term.”
In addition to metoclopramide, erythromycin is used off-label for its prokinetic properties, but its efficacy is also limited. Adeling Hung, MD, emphasizes that available prokinetics, including metoclopramide and erythromycin, exhibit modest effectiveness and significant side effects.
With a critical need for new treatments, Vanda Pharmaceuticals has sought to introduce a novel therapy, tradipitant, a neurokinin receptor 1 antagonist. However, in September 2024, the FDA issued a Complete Response Letter (CRL) for Vanda’s New Drug Application, requesting further studies that do not align with expert recommendations.
The CRL leaves metoclopramide as the only approved treatment for gastroparesis, raising questions about the path forward for effective therapies. Experts like Hung argue for the necessity of redefining gastroparesis, suggesting it may be more accurately understood as a sensory disorder for many patients rather than solely a motility issue.
This perspective is gaining traction, as Lacy suggests that reframing gastroparesis could lead to new treatment pathways, such as the use of targeted devices or medications that address sensory dysfunction.
The exploration of device-based therapies is also gaining momentum. Techniques like gastric electrical stimulation and vagal nerve stimulation are emerging as potential treatments for nausea and motility control. These methods are customizable, allowing for personalized care. Weinstein explains that a temporary stimulation trial can help determine which patients are likely to benefit from such interventions.
Despite the promise of these approaches, Hung cautions that standardization in integrating novel treatments with pharmacotherapy is essential for optimal patient outcomes. She states, “This could be an exciting area of research in the future.”
As the medical community continues to navigate the complexities of gastroparesis, there is hope for meaningful advancements. Redefining the condition, incorporating patient-reported outcomes into clinical trials, and advancing device-based therapies may bridge the existing gaps in treatment. The growing recognition of gastroparesis’ heterogeneity suggests that a new era in patient care may be on the horizon, offering long-awaited solutions for those suffering from this challenging disorder.