Nortriptyline for the Treatment of Functional Dyspepsia

Inclusion Criteria:

• Age 18-65 years;

• A diagnosis of FD according to the Rome IV criteria;

• Predicted CYP2D6 extensive metabolizer phenotype on the basis of CYP genotyping

• Insufficient effect of first line treatment with proton pump inhibitors (twice daily)or prokinetics;

• In the presence of alarm symptoms, patients are required to have undergone an uppergastrointestinal endoscopy (without evidence of organic disease), and have testednegative for Helicobacter pylori 2 years prior to inclusion;

• Women in their fertile age (<55 years old) must use contraception or be postmenopausalfor at least two years.

Exclusion Criteria:

• Predicted CYP2D6 poor, intermediate or ultrarapid metabolizer phenotype on the basisof CYP genotyping

• Evidence of current anxiety and/or depression disorder as defined by a score ≥ 10 onthe GAD-7 and/or PHQ-9 questionnaire;

• Current use or any previous use of psychotropic medication in the last 3 months priorto inclusion;

• Inability to discontinue prokinetics, NSAIDs or opioids;

• Using drugs of abuse;

• Using more than 2 or 3 units of alcohol per day (females and males respectively)

• Previous major abdominal surgery or radiotherapy interfering with gastrointestinalfunction:

1. Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unlesswithin the past 6 months;

2. Other surgery upon judgment of the principle investigator;

• History of gastric ulcer;

• History of liver disease, cholangitis, achlorhydria, gallstones or other diseases ofthe gallbladder/biliary system;

• History of epilepsy

• History of glaucoma

• Pregnancy or lactation.