Effects of Amitriptyline on Gastric Sensorimotor Function and Postprandial Symptoms in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial

Bouras, Ernest P.; Talley, Nicholas J.; Camilleri, Michael; Burton, Duane D.; Heckman, Michael G.; Crook, Julia E.; Richelson, Elliott

doi:10.1111/j.1572-0241.2008.02021.x

Cited by 49 publications

(40 citation statements)

References 58 publications

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“…This was in agreement with a previous study in which a TCA, amitriptyline, slowed gastric solid emptying at 2 and 4 h in healthy volunteers (2). However, another study reported that mianserin, a tetracyclic antidepressant, did not affect solid or liquid gastric emptying (14).…”

Section: Discussionsupporting

confidence: 81%

“…Antidepressants are widely prescribed in patients with FD in clinic (12,33,38). These drugs may modulate several aspects in FD such as improving psychiatric and psychological conditions, influencing central regulation of visceral pain stimuli, and modifying gut sensorimotor function (2)(3)(4). In previous studies, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were used to treat FD (21,37,43).…”

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confidence: 99%

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Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

Dai

Lei

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Desvenlafaxine succinate (DVS) is a novel serotonin and norepinephrine reuptake inhibitor. The aim of this study was to investigate the effects of DVS on visceral hypersensitivity and solid gastric emptying in a rodent model of gastric hyperalgesia. Twenty-eight gastric hyperalgesia rats and 20 control rats were used. Visceral sensitivity during gastric distention (GD) was assessed by recording of electromyogram (EMG) at pressures of 20, 40, 60, and 80 mmHg. DVS with doses of 1, 10, and 30 mg/kg were administrated by gavage, 5-HT1A antagonist (WAY-100635, 0.3 mg/kg) was given subcutaneously, and 5-HT2A antagonist (ketanserin, 1 mg/kg) was given intraperitoneally. The level of norepinephrine in plasma was measured by enzymelinked immunosorbent assay. We found that 1) visceral hypersensitivity induced by acetic acid was validated. 2) DVS dose-dependently reduced visceral hypersensitivity in the gastric hypersensitivity rats. The EMG (% of baseline value without GD) during GD at 60 and 80 mmHg with DVS at a dose of 30 mg/kg were 119.4 Ϯ 2.3% (vs. saline 150.9 Ϯ 2.7%, P Ͻ 0.001) and 128.2 Ϯ 3.2% (vs. saline 171.1 Ϯ 2.4%, P Ͻ 0.001). Similar findings were observed at a dose of 10 mg/kg. DVS at a dose of 1 mg/kg reduced visceral hypersensitivity only during GD at 60 mmHg. 3) Neither WAY-100635 nor ketanserin blocked the effect of DVS on visceral sensitivity. 4) DVS at 30 mg/kg significantly increased plasma NE level (P ϭ 0.012 vs. saline). 5) DVS at 30 mg/kg significantly delayed solid gastric emptying (P Ͻ 0.05 vs. saline). We conclude that DVS reduces visceral sensitivity in a rodent model of visceral hypersensitivity and delays solid gastric emptying. Caution should be made when DVS is used for treating patients.antidepressant; visceral hypersensitivity; gastric emptying; desvenlafaxine succinate FUNCTIONAL DYSPEPSIA (FD) is a common clinical gastrointestinal disease with a high prevalence throughout the world (23, 27), defined as pain or discomfort located in the upper abdomen without evidence of organic structural abnormalities that can explain the symptoms (36). FD is considered to be a biopsychosocial disorder with visceral hypersensitivity, impaired gastroduodenal motility, and central nervous system disturbance (34, 35). Psychosocial factors can affect visceral sensation and gut motility (34,35). Antidepressants are widely prescribed in patients with FD in clinic (12,33,38). These drugs may modulate several aspects in FD such as improving psychiatric and psychological conditions, influencing central regulation of visceral pain stimuli, and modifying gut sensorimotor function (2-4). In previous studies, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were used to treat FD (21, 37, 43).Desvenlafaxine succinate (DVS) is the third serotonin-norepinephrine reuptake inhibitor approved by the Food and Drug Administration for the treatment of major depressive disorders in 2008 (19). It increases the level of serotonin (5-HT) and norepinephrine (NE) by blocking the presynaptic reup...

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

Dai

Lei

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Second, antidepressants have central analgesic actions and alter central processing of visceral pain stimuli (10, 27). Third, antidepressants may have local pharmacological actions on the gut and modulate gut sensorimotor functions (3,8,9).Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, the third serotonin-norepinephrine reuptake inhibitor (SNRI) approved by the U.S. Food and Drug Administration for the treatment of major depressive disorders in 2008 (26, 35). It is a novel salt form of the isolated major active metabolite of the antidepressant venlafaxine.…”

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confidence: 99%

mentioning

confidence: 99%

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Dai¹,

Lei²,

Chen

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, serotonin-norepinephrine reuptake inhibitor. Antidepressants have been widely used for the treatment of functional gastrointestinal disorders. Possible roles of DVS on gastrointestinal motility have not been studied. The aim of this study was to investigate the effects of DVS on gastric slow waves (GSW), antral contractions, and gastric accommodation in dogs. Fifteen healthy dogs implanted with gastric serosal electrodes and a gastric cannula were studied in four separate sessions: control, DVS (50 mg), propranolol (1 mg·kg Ϫ1 ·h Ϫ1 ), and propranolol ϩ DVS. GSW were measured via the gastric serosal electrodes. Antral contractions were assessed via an intraluminal manometric catheter inserted via the gastric cannula. The sympathovagal activity was assessed from the spectral analysis of the heart rate variability signal. Gastric tone was measured by barostat via an intragastric balloon inserted into the fundus via the gastric cannula. In the postprandial period, in comparison with the control, DVS reduced the percentage of normal GSW (P ϭ 0.001) and increased the percentage of tachygastria (P ϭ 0.005) and bradygastria (P ϭ 0.002). Simultaneously, DVS increased the sympathetic activity (P ϭ 0.006) and the sympathovagal ratio (low frequency/high frequency; P ϭ 0.044). These effects were blocked by propranolol. DVS attenuated postprandial antral contractions and gastric accommodation. The postprandial antral contractile index (area under the curve) was decreased by 26% with DVS (P ϭ 0.013), and gastric accommodation was decreased by about 50% with DVS (P Ͻ 0.001). The inhibitory effect of DVS on gastric accommodation was blocked by propranolol. DVS inhibits gastric contractions, slow waves, and accommodation in the fed state. These inhibitory effects are associated with an increased sympathetic modulation in the gastrointestinal system. Cautions should be made when DVS is used for treating patients with depression and gastric motility disorders. desvenlafaxine succinate; antidepressants; gastrointestinal motility ANTIDEPRESSANTS ARE WIDELY used for the treatment of functional gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome (17,20,55). The rationale for the use of antidepressants in functional gastrointestinal disorders is based on the following potential effects. First, antidepressants may improve psychiatric and psychological symptoms, particularly anxiety and depression (11,18,47). Second, antidepressants have central analgesic actions and alter central processing of visceral pain stimuli (10, 27). Third, antidepressants may have local pharmacological actions on the gut and modulate gut sensorimotor functions (3,8,9).Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, the third serotonin-norepinephrine reuptake inhibitor (SNRI) approved by the U.S. Food and Drug Administration for the treatment of major depressive disorders in 2008 (26, 35). It is a novel salt form of the isolated major active metab...

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“…Known prokinetic medications include metoclopramide, domperidone, erythromycin and cholinergic medications such as bethanechol [14][15][16][17][18][19][20]. Medications known to slow gastric emptying include opioid narcotics, tramadol, tricyclic antidepressants, calcium channel blockers, dopamine agonists, octreotide, anticholinergics, clonidine, and phenothiazines [14,[21][22][23][24][25][26][27][28][29][30][31][32][33]. Nicotine has also been shown to slow gastric emptying [13,34,35].…”

Section: Introductionmentioning

confidence: 99%

Outpatient vs. Inpatient Gastric Emptying Studies: Does Admission Status Influence Findings?

Holmes¹,

Kim²,

Prather³

et al. 2015

J Hepatol Gastroint Dis

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Objectives: Gastric emptying studies are performed in both outpatient and inpatient settings. Although there is no data on the prevalence of positive and negative testing between inpatient and outpatient studies, some feel inpatient testing is inappropriate secondary to potential false positives. We aim to identify the incidence and determinants of abnormal studies for inpatient versus outpatient gastric emptying studies. Methods:A retrospective chart review of scintigraphic gastric emptying studies was performed between June 1, 2012 and April 11, 2014. Demographics, clinical information, and procedure details were collected. Descriptive statistics were used to report findings with categorical variables analyzed using Pearson Chi-Square test and continuous variables analyzed with independent samples t-test. All statistical analyses were performed using IBM SPSS Statistics version 21.0 software.Results: 107 GE studies were reviewed (34 inpatient, 73 outpatient). Six incomplete studies were excluded. Mean patient age was 51 years (64% female, 60% Caucasian). There were more women than men in the outpatient population (p=0.04). The inpatient studies had a higher percentage of African Americans while the outpatient studies were mostly Caucasian (p=0.002). There were no other demographic differences between the inpatient and outpatient groups. The most common indication for testing was nausea and/or vomiting (44%). 42 (22 inpatient, 20 outpatient) tests were positive and 59 (8 inpatient, 51 outpatient) were negative for impaired gastric emptying. Inpatient GE testing was abnormal 73% of the time, while outpatient GE testing was abnormal 28% of the time (p<0.01). Review of inpatient GE studies revealed 97% patients received a medication known to alter gastric motility and 67% received opioid narcotics within 72 hours of testing. Patients with diabetes were 2.28 times more likely to have a positive test than patients without diabetes. Half of the abnormal tests were found in patients with diabetes. Conclusions:Abnormal gastric emptying studies are more commonly found in inpatient studies. A majority of inpatient studies are performed on patients who have received medications known to delay gastric motility and may be at an increased risk for false positives.

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Effects of Amitriptyline on Gastric Sensorimotor Function and Postprandial Symptoms in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial

Cited by 49 publications

References 58 publications

Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Outpatient vs. Inpatient Gastric Emptying Studies: Does Admission Status Influence Findings?

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