Nortriptyline for the Treatment of Functional Dyspepsia
Nortriptyline for the Treatment of Functional Dyspepsia
Functional dyspepsia (FD) is a common functional gastrointestinal disorder characterized by
 upper abdominal discomfort/pain and/or symptoms of meal-related fullness/satiety. There is
 currently no definitive therapy that is beneficial for all FD patients. Accumulating evidence
 suggests efficacy of tricyclic antidepressants (TCAs) in FD. However, no firm conclusion can
 be drawn currently due to the relatively small amount of studies and large heterogeneity
 between studies. In addition, TCAs are often associated with side effects, which occur early
 after initiation of therapy preceding the therapeutic effect and often result in
 discontinuation of the therapy. These side effects are related to drug metabolism, which
 depend on polymorphisms of the cytochrome P (CYP) enzyme system. It is therefore hypothesized
 that pre-treatment assessment of CYP genotype and subsequent exclusion of abnormal
 metabolizers limits the occurrence of side-effects and as such improves compliance and
 efficacy.
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 upper
 gastrointestinal endoscopy (without evidence of organic disease), and have tested
 negative for Helicobacter pylori 2 years prior to inclusion;

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

 Exclusion Criteria:

 -  Predicted CYP2D6 poor, intermediate or ultrarapid metabolizer phenotype on the basis
 of CYP genotyping

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

 -  Current use or any previous use of psychotropic medication in the last 3 months prior
 to 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 gastrointestinal
 function:

 1. Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless
 within 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 of
 the gallbladder/biliary system;

 -  History of epilepsy

 -  History of glaucoma

 -  Pregnancy or lactation.