Successful Treatment of Refractory Gastroparesis-related Nausea in Parkinson’s Disease with Mirtazapine
Objective:
To highlight the potential role of off-label mirtazapine in treating refractory gastroparesis-related nausea in Parkinson’s disease (PD), thereby expanding current approaches to non-motor symptom management and contributing to the growing literature on therapeutic strategies.
Background:
Gastrointestinal symptoms are among the most prevalent non-motor manifestations in PD, significantly contributing to morbidity. While constipation and dysphagia are commonly recognized, nausea secondary to gastroparesis remains difficult to manage. The underlying pathophysiology is multifactorial, involving dysregulation of the brain-gut axis, vagal nerve dysfunction, and alpha-synuclein deposition within the enteric nervous system. These disruptions impair gastric motility and contribute to refractory symptoms. Pharmacologic options for managing gastroparesis-related nausea in PD are limited, and treatment is often suboptimal. This case highlights the successful off-label use of mirtazapine as a therapeutic alternative.
Design/Methods:
An 81-year-old man with idiopathic PD (diagnosed in 2021) presented in March 2024 with one month of persistent daytime nausea occasionally disrupting sleep. He denied constipation but noted unintentional weight loss. Proton pump inhibitors and ondansetron were ineffective. Importantly, nausea occurred independently of levodopa dose timing and did not improve with typical management including additional carbidopa, reduction of dopaminergic medications, or administration with food, suggesting symptoms were unrelated to dopaminergic therapy. EGD revealed a 14 mm GE junction stricture (dilated to 15–18 mm) and a 4 cm hiatal hernia. A gastric emptying study confirmed mild gastroparesis. Trials of CBD/THC, scopolamine, and vagal nerve stimulation (GammaCore) provided limited benefit. Mirtazapine 7.5 mg nightly was initiated, later titrated to 15 mg.
Results:
At 7.5 mg, nausea improved substantially; at 15 mg, episodes decreased from daily severe to mild, brief symptoms every other day.
Conclusions:
Mirtazapine may offer a valuable off-label option for treating refractory nausea related to gastroparesis in PD. Its multimodal serotonergic and noradrenergic effects may enhance gastric motility and antiemetic response where standard agents fail.
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