Intervention: Amitriptyline
Trial phase: Phase 2 | Phase 3
ATC code: N06AA09 | N06CA01
SMILES: CN(C)CCC=C1c2ccccc2CCc2ccccc21
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 97
Group description: Amitriptyline capsule (50 mg) plus a placebo escitalopram tablet will be taken at night half an hour before bedtime. To maximize patient tolerability, in the first 2 weeks the dose of amitriptyline will be 25 mg and then the dose will be increased to 50 mg, but the 25 mg and 50 mg capsules will be indistinguishable to maintain blinding.
Eligibility criteria:
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.