Functional Dyspepsia Treatment Trial

The aims of this study were to:

• Determine whether antidepressant therapy is more efficacious than placebo in relief of the symptoms of functional dyspepsia, adjusting for psychological and psychiatric co-morbidity. The investigators also planned to determine if antidepressant therapy reduces disability, improves quality of life and influences clinical response over 6 months after ceasing medication.
• Determine if gastric emptying (motor dysfunction) and the nutrient drink test (a test that assesses gastric hypersensitivity and/or gastric accommodation) is altered by antidepressant therapy with a tricyclic or selective serotonin re-uptake inhibitors (SSRI), and whether subgroups with altered physiology are associated with treatment outcome.

Inclusion criteria

• Normal esophagogastroduodenoscopy (EGD) (no esophagitis, Barrett's esophagus, cancer, erosions, or ulcer disease) within the past 5 years
• Diagnosis of functional dyspepsia
• Patients may have failed to adequately respond to antisecretory therapy in the past for functional dyspepsia to be suitable; a good response to antisecretory therapy, which remains first line therapy, suggests underlying gastroesophageal reflux disease (GERD).

Exclusion criteria

• Any documented history of endoscopic esophagitis, or predominant heartburn or acid regurgitation, or these symptoms two or more times per week in the prior year, to exclude GERD.
• Those who have had an adequate response to antisecretory therapy according to the physician interview, to exclude patients with disease easy to control with first line therapy or misdiagnosed GERD.
• Any documented peptic ulcer disease.
• Regular use of non-steroidal anti-inflammatory drugs (except long term low dose aspirin ≤ 325 mg / day)
• Subjects undergoing psychiatric treatment, having a current history of drug or alcohol abuse, or currently taking psychotropic medication for depression or psychosis, or eating disorders
• A history of abdominal surgery except appendectomy, cholecystectomy or hysterectomy, tubal ligations, bladder slings, and vasectomies
• Subjects with concurrent major physical illness (including cardiac or liver disease, diabetes, inflammatory bowel disease, glaucoma, urinary retention, active thyroid disease, vasculitis, lactose intolerance explaining symptoms)
• Subjects whose literacy skills are insufficient to complete self report questionnaires.
• Pregnancy, or refusal to apply adequate contraceptive measures during the trial
• Subjects currently on antidepressant therapy will be excluded.
• Patients who score 11 or greater on the 7 questions related to depression of the Hospital Anxiety Depression Scale will be excluded. These patients will be encouraged to get follow up for depression.
• All eligible patients over age 50 will have an EKG before randomization. Those found to have significant arrhythmias, conduction defects or a previous myocardial infarction on EKG will be excluded. Anyone with QT prolongation will be excluded.

The following concomitant medications will be prohibited during the trial:

• Systemically acting cholinergics and anticholinergics (atropine, didinium bromide, propantheline)
• Prokinetics (e.g., metoclopramide, tegaserod)
• Macrolide antibiotics (e.g., erythromycin, azithromycin)
• Aspirin (> 325 mg/day)
• Spasmolytics (e.g., dicyclomine)
• Antidepressants other than study medications
• Serotonin enhancing drugs: monamine oxidase inhibitors, anticonvulsants, dextromethorphan.

Participants will be instructed to avoid grapefruit/grapefruit juice during the trial.