• To assess if Nortriptyline improves quality of life in patients with nonulcer dyspepsia [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• To assess frequency of side effects in patients receiving Nortriptyline for nonulcer dyspepsia [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

• To assess if Nortriptyline improves quality of life in patients with nonulcer dyspepsia [ Time Frame: 8 weeks ]
• To assess frequency of side effects in patients receiving Nortriptyline for nonulcer dyspepsia [ Time Frame: 8 weeks ]

The purpose of this study is to determine if use of Nortriptyline will improve symptoms and quality of life in patients who have nonulcer dyspepsia.

Nonulcer dyspepsia is a common complaint in clinical practice and its management should be based on the best evidence. Many clinical trials of nonulcer dyspepsia suffer from important weaknesses in trial design. This makes it difficult to determine whether truly efficacious therapies exist for this disorder.

Once a diagnosis of nonulcer dyspepsia is confirmed by normal endoscopy, a trial of therapy is commonly prescribed. However, the benefits of all therapies in this condition have been questioned. Small studies have suggested benefit in use of antidepressants such as Nortriptyline and even though the data is insufficient, antidepressants such as Nortriptyline are widely used in clinical practice largely due to lack of proven, reliable therapies for nonulcer dyspepsia.

Our hypothesis is that Nortriptyline will improve symptoms of nonulcer dyspepsia and improve quality of life.

• Drug: Nortriptyline
• Drug: Placebo

• Active Comparator: Patients in this group will receive Nortriptyline 25mg at night for 8 weeks.
• Placebo Comparator: Patients in this group will receive an identical placebo capsule at night for 8 weeks.

• Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer EA. Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. Am J Gastroenterol. 1998 Feb;93(2):160-5.
• Tanum L, Malt UF. A new pharmacologic treatment of functional gastrointestinal disorder. A double-blind placebo-controlled study with mianserin. Scand J Gastroenterol. 1996 Apr;31(4):318-25.
• Wiklund IK, Junghard O, Grace E, Talley NJ, Kamm M, Veldhuyzen van Zanten S, Pare P, Chiba N, Leddin DS, Bigard MA, Colin R, Schoenfeld P. Quality of Life in Reflux and Dyspepsia patients. Psychometric documentation of a new disease-specific questionnaire (QOLRAD). Eur J Surg Suppl. 1998;(583):41-9.
• Veldhuyzen van Zanten SJ, Chiba N, Armstrong D, Barkun AN, Thomson AB, Mann V, Escobedo S, Chakraborty B, Nevin K. Validation of a 7-point Global Overall Symptom scale to measure the severity of dyspepsia symptoms in clinical trials. Aliment Pharmacol Ther. 2006 Feb 15;23(4):521-9.
• Hojo M, Miwa H, Yokoyama T, Ohkusa T, Nagahara A, Kawabe M, Asaoka D, Izumi Y, Sato N. Treatment of functional dyspepsia with antianxiety or antidepressive agents: systematic review. J Gastroenterol. 2005 Nov;40(11):1036-42. Review.
• Veldhuyzen van Zanten SJ, Cleary C, Talley NJ, Peterson TC, Nyren O, Bradley LA, Verlinden M, Tytgat GN. Drug treatment of functional dyspepsia: a systematic analysis of trial methodology with recommendations for design of future trials. Am J Gastroenterol. 1996 Apr;91(4):660-73.
• Talley NJ, Vakil N; Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the management of dyspepsia. Am J Gastroenterol. 2005 Oct;100(10):2324-37.
• Jackson JL, O'Malley PG, Tomkins G, Balden E, Santoro J, Kroenke K. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med. 2000 Jan;108(1):65-72.
• Talley NJ. Therapeutic options in nonulcer dyspepsia. J Clin Gastroenterol. 2001 Apr;32(4):286-93. Review.
• Talley NJ, Fullerton S, Junghard O, Wiklund I. Quality of life in patients with endoscopy-negative heartburn: reliability and sensitivity of disease-specific instruments. Am J Gastroenterol. 2001 Jul;96(7):1998-2004.
• Design of Treatment Trials Committee; Irvine EJ, Whitehead WE, Chey WD, Matsueda K, Shaw M, Talley NJ, Veldhuyzen van Zanten SJ. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology. 2006 Apr;130(5):1538-51. Review.
• Veldhuyzen van Zanten SJ, Talley NJ, Bytzer P, Klein KB, Whorwell PJ, Zinsmeister AR. Design of treatment trials for functional gastrointestinal disorders. Gut. 1999 Sep;45 Suppl 2:II69-77.
• Moayyedi P, Delaney BC, Vakil N, Forman D, Talley NJ. The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis. Gastroenterology. 2004 Nov;127(5):1329-37. Review.

Inclusion Criteria:

• Men and Women
• Ages 18-65
• Meet Rome III criteria for functional dyspepsia
• Endoscopy within 1 year

Exclusion Criteria:

• Allergic reaction or history of adverse events with Nortriptyline or tricyclic antidepressants
• Organic cause found on physical examination
• Organic cause found on lab work: CBC, CMP, TSH, Tissue transglutaminase IgA
• Predominantly GERD symptoms
• Current Helicobacter pylori infection
• History of PUD
• NSAID use > 2x/wk
• Pregnant or planning pregnancy
• History of major depression
• Abdominal surgery in the last year