Gastroesophageal reflux disease (GERD) is a common chronic digestive system disorder with a high prevalence and a notably increasing trend. It imposes significant costs in terms of treatment expenses and impacts patients' quality of life. Acid suppression remains the primary treatment for GERD. However, numerous clinical studies have shown that 20-30% of patients still exhibit poor response to proton pump inhibitors (PPIs) even after completing a standard course of acid-suppressive therapy. Many studies have demonstrated that the incidence of abnormal psychological conditions, such as anxiety, depression, and obsessive-compulsive disorder, is higher in GERD patients compared to the general population. Current international consensus acknowledges that the application of psychosomatic medicine principles and the use of neuromodulators can effectively alleviate symptoms in patients with gut-brain interaction disorders. Nevertheless, with the growing emphasis on digestive-psychosomatic-holistic medicine in clinical practice and the deepening of research on "gut-brain interactions," recent studies in the field of psycho-gastroenterology have challenged the notion that psychological processes are unique to gut-brain interaction disorders. Instead, these processes may play a universal role in symptom generation across the entire spectrum of GERD. Previous experiments have confirmed that Flupentixol-Melitracen (FM) can improve symptoms in GERD patients with a low incidence of adverse reactions. Therefore, we aim to verify the efficacy and safety of neuromodulators in patients with GERD, reduce healthcare costs, and provide new insights for optimizing treatment strategies for GERD patients in the future.

Inclusion Criteria:

- Adults aged 18-70 years with gastroesophageal reflux disease (GERD) meeting diagnostic criteria.

Exclusion Criteria:

• Patients with organic gastrointestinal disorders (e.g., celiac disease, inflammatory bowel disease, history of gastrointestinal malignancies);

Severe dysfunction of major organs (e.g., class IV cardiac dysfunction, hepatic failure, uremia, respiratory failure) or congenital diseases (e.g., hemophilia, Wilson's disease);

Hypersensitivity to study medications;

Patients who are pregnant, lactating, or planning pregnancy;

Use of monoamine oxidase inhibitors (e.g., linezolid or intravenous methylene blue) within the past 5 weeks;

Severe psychological symptoms or cognitive impairment (GAD-7 >15 or PHQ-9 ≥15);

Circulatory failure, central nervous system depression (e.g., acute alcohol, barbiturate, or opioid intoxication), or coma.