S1115 Mirtazapine for Refractory Gastroparesis: A Systematic Review of Symptom Relief and Therapeutic Potential

Introduction: Gastroparesis is a chronic gastrointestinal motility disorder that leads to delayed gastric emptying in the absence of mechanical obstruction, causing symptoms like nausea, vomiting, bloating, and early satiety. Standard therapies often fail in refractory cases. Mirtazapine, a noradrenergic and specific serotonergic antidepressant with appetite-stimulating and antiemetic properties, has shown promise in symptom control. This systematic review aims to evaluate the efficacy and safety of mirtazapine in patients with refractory gastroparesis. Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase, and Scopus were searched using the terms “mirtazapine,” “gastroparesis,” “delayed gastric emptying,” “nausea,” and “appetite.” Eligible studies included adult patients with refractory gastroparesis treated with mirtazapine and reporting clinical outcomes. Study designs included randomized controlled trials, prospective and retrospective studies, case series, and case reports. Extracted data included sample size, dosage, symptom improvement, and adverse effects. Methodological quality was assessed using CASP tools. Results: Twenty-three studies met inclusion criteria: 3 randomized controlled trials, 5 prospective studies, 4 retrospective studies, 7 case series, and 4 case reports. Sample sizes ranged from 1 to 42. Across studies, mirtazapine was consistently associated with improvements in nausea, vomiting, appetite, caloric intake, and weight gain. Commonly used doses ranged from 15–30 mg at bedtime. Sedation and weight gain were the most frequently reported side effects, typically well tolerated. Heterogeneity in study design and outcome measures limited meta-analytic synthesis. Conclusion: This review suggests mirtazapine may be a safe and effective off-label option for managing refractory gastroparesis, particularly in patients with nausea and poor oral intake. Its mechanism likely involves 5-HT3 receptor antagonism and central appetite stimulation. However, the predominance of small, non-randomized studies and the lack of standardized symptom assessment underscore the need for larger, controlled trials. Future research should define optimal dosing, identify patient subgroups most likely to benefit, and establish long-term efficacy and safety profiles.