Gastro-esophageal reflux disease (GERD) is highly prevalent, affecting up to 20% of the adult population in North America. Up to 70% of GERD patients have non-erosive reflux disease (NERD), a term used to describe symptoms suggestive of GERD in patients with no endoscopic evidence of erosive esophagitis. NERD represents a heterogeneous group of patients whom are sub classified according to 24 hours-PH monitoring results and also symptom-acid association analysis(Symptom Index,SI).

Treatment of NERD can be a challenge for clinicians. According to the many studies , the pooled rate for symptomatic response after a period of proton pomp inhibitor(PPIs)therapy as the most frequently used drug, in NERD patients is lower than for erosive esophagitis patients. It is also shown that acid exposure is much lower in NERD patients than those with erosive esophagitis and NERD patients are less likely to exhibit a strong association between heartburn symptoms and acid reflux events than patients with erosive oesophagitis.

Furthermore, beside the high economic burden, there are concerns about the adverse effects of long time administration of PPIs.

Several hypothesis has been proposed to describe low response rate of NERD patients to PPIs. One of the most acceptable theories is that patients with anxiety or depression and psychological problems are at an increased risk of developing reflux symptoms. On the other hand, pain modulators such as sertraline, a selective serotonin reuptake inhibitor(SSRI), and other antidepressants have been shown to improve symptoms in patients with functional gastrointestinal disorders like non cardiac chest pain.

According to the above-mentioned tips, the investigators hypothesize that antidepressants like fluoxetine, as an SSRI, may have beneficial effects in improving symptoms of NERD patients.

The purpose of this study is to compare the effect of omeprazole with fluoxetine and placebo for treatment of NERD patients and its subgroups who all experience reflux symptoms and have normal endoscopic findings.

Inclusion Criteria:

• age above 18 and below 60 years old
• experiencing heartburn during last 6 months before inclusion
• experiencing heartburn during at least 4 of 7 days before inclusion
• presence of normal mucosa in upper gastrointestinal(GI) endoscopy which has been documented during 7 days before inclusion provided that the patient has not administered any PPI during last 30 days before inclusion

Exclusion Criteria:

• inability to undergone upper GI endoscopy or PH monitoring
• presence of barret's esophagus or erosive esophagitis in upper GI endoscopy
• presence of active peptic ulcer disease or any disease which affects the absorption of drugs such as inflammatory bowel disease
• past history of esophageal or gastric surgery
• esophageal stricture which needs dilation
• administration of proton pomp inhibitors during 30 days before inclusion to the study
• administration of H2 blockers, anticholinergics, sucralfate and pro-kinetics during the assessments for eligibility and also during the study
• long time administration of non-steroidal anti-inflammatory drugs (NSAIDs)
• administration of neuroleptic or antidepressant drugs during 30 days before inclusion to the study
• known allergy to PPIs or SSRIs
• presence of significant systemic disease such as scleroderma , diabet mellitus , peripheral and autonomic neuropathies and ...
• pregnancy for females
• presence of known psychiatric disorder such as depression , panic disorder or drug addiction according to the DSM-IV criteria