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Tricyclic antidepressants in low doses are widely used in the therapy of patients with functional gastrointestinal disorders, yet the mechanism(s) of action of these drugs in these disorders is not known. In the current study, we sought to determine in a group of patients with functional dyspepsia and associated poor sleep how amitryptiline affects digestive symptoms, perceptual responses to gastric distension, and subjective and objective measures of sleep.Patients were randomized to 4 wk of amitryptiline 50 mg taken at bedtime versus placebo. There was a 3-wk washout phase, followed by a cross-over to the alternate treatment. Perceptual sensitivity to gastric distention and sleep EEG were recorded at the end of each treatment period. Diaries of symptoms were maintained throughout.Seven of seven patients reported significantly less severe gastrointestinal symptoms after 4 wk on amitryptiline compared to placebo. Five of seven patients had evidence for altered perception of gastric balloon distension during placebo. However, the subjective symptom improvement on amitryptiline was not associated with a normalization of the perceptual responses to gastric distension. Baseline sleep dysfunction in the form of reduced sleep efficiency, increased arousal, or abnormal amounts of REM sleep was found in all seven patients. Amitryptiline significantly reduced absolute and relative amounts of REM sleep, but had no effect on sleep parameters related to nonregenerative sleep.The beneficial effect of low dose amitryptiline seen in functional dyspepsia is not related to changes in perception of gastric distension, or to measures of arousal from sleep. An increased tolerance to aversive visceral sensations may play a role in the therapeutic effect.