title: Anxiety is associated with uninvestigated and functional dyspepsia (Rome III criteria) in a Swedish population-based study. Visceral and somatic sensory function in functional dyspepsia. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Treatment of functional dyspepsia with sertraline: a double-blind randomized placebo-controlled pilot study. Effects of Amitriptyline on Gastric Sensorimotor Function and Postprandial Symptoms in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial A placebo-controlled trial of the 5-HT1A agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia. Clinical Guideline: Management of Gastroparesis Dyspeptic patients with visceral hypersensitivity: sensitisation of pain specific or multimodal pathways? Effects of Levosulpiride in Patients with Functional Dyspepsia Accompanied by Delayed Gastric Emptying Efficacy of the 5-HT1A Agonist Tandospirone Citrate in Improving Symptoms of Patients With Functional Dyspepsia: A Randomized Controlled Trial Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study. The eflects of levosulpiride on gastric and gall‐bladder emptying in functional dyspepsia Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double-blind, placebo-controlled trial. Influence of the selective serotonin re‐uptake inhibitor, paroxetine, on gastric sensorimotor function in humans Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials A new pharmacologic treatment of functional gastrointestinal disorder. A double-blind placebo-controlled study with mianserin. Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Comparative effects of levosulpiride and cisapride on gastric emptying and symptoms in patients with functional dyspepsia and gastroparesis Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. The effects of acute citalopram dosing on gastric motor function and nutrient tolerance in healthy volunteers Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.
abstract: BACKGROUND & AIMS The Rome III criteria for functional dyspepsia have been changed to include 2 distinct syndromes : postpr and ial distress syndrome and epigastric pain syndrome . We investigated risk factors for functional dyspepsia among the functional dyspepsia subgroups defined by the Rome III criteria . METHODS We performed a cross-sectional population -based study in a primary care setting ( the Kalix and a study ) . A r and om sample ( n = 2860 ) of the adult population from 2 northern Swedish municipalities ( n = 21,610 ) was surveyed using a vali date d postal question naire to assess gastrointestinal symptoms ( response rate , 74.2 % ; n = 2122 ) . A r and omly selected subgroup ( n = 1001 ) of responders was invited to undergo an esophagogastroduodenoscopy ( participation rate , 73.3 % ) including biopsy specimen collection , Helicobacter pylori culture and serology , and symptom assessment s. RESULTS Of the 1001 subjects examined by endoscopy , 202 ( 20.2 % ; 95 % confidence interval [ CI ] , 17.7 - 22.7 ) were classified as having uninvestigated dyspepsia and 157 ( 15.7 % ; 95 % CI , 13.4 - 18.0 ) as having functional dyspepsia . Major anxiety ( Hospital Anxiety and Depression Scale score > or = 11 ) was associated with uninvestigated dyspepsia ( odds ratio [ OR ] , 3.01 ; 95 % CI , 1.39 - 6.54 ) , as was obesity ( body mass index > or = 30 kg/m(2 ) ) ( OR , 1.86 ; 95 % CI , 1.15 - 3.01 ) . Major anxiety was associated with functional dyspepsia and postpr and ial distress syndrome ( OR of 2.56 [ 95 % CI , 1.06 - 6.19 ] and 4.35 [ 95 % CI , 1.81 - 10.46 ] , respectively ) , as was use of nonsteroidal anti-inflammatory drugs ( OR , 2.49 [ 95 % CI , 1.29 - 4.78 ] and 2.75 [ 95 % CI , 1.38 - 5.50 ] , respectively ) . Depression was not associated with any dyspepsia group . CONCLUSIONS Anxiety but not depression is linked to uninvestigated dyspepsia , functional dyspepsia , and postpr and ial distress syndrome but not to epigastric pain syndrome BACKGROUND Visceral hypersensitivity is one of the proposed underlying mechanisms in functional dyspepsia ( FD ) . It is not clear whether visceral hypersensitivity in FD is a manifestation of a central sensitization also encompassing somatic sensitization . Transient receptor potential vanilloid-1 ( TRPV(1 ) ) pathways are involved in gastric mechanosensory physiology and the TRPV(1 ) receptor agonist , capsaicin , has been used as a chemical stimulant . METHODS In this double-blind , r and omized study we evaluated both visceral and somatic sensory function in 34 FD patients and 42 healthy controls using quantitative sensory testing . Visceral pain sensitivity was assessed using a vali date d gastric pain model with oral capsaicin capsule titration and somatic pain sensitivity was determined by foot heat and h and electric stimulation . KEY RESULTS The median capsaicin dose required to attain moderate pain was 0.5 mg in FD and 1 mg in controls ( P = 0.03 ) . At these doses , mean pain intensities on a 0 - 100 visual analog scale were greater for FD than controls [ 56.9 ( 95 % confidence intervals , 52.2 - 61.5 ) vs 45.1 ( 41.6 - 48.6 ) , resp . ] ( P = 0.005 ) . Overall , mean somatic sensory and pain thresholds were similar in FD and control groups , but in a subgroup of FD pain hypersensitivity was seen on the h and and on the foot at different stimulation thresholds . CONCLUSIONS & INFERENCES A majority of patients with FD have visceral chemo-hypersensitivity involving TRPV(1 ) pathways . A substantial subgroup also has somatic hypersensitivity as evidence of central sensitization BACKGROUND & AIMS Functional abnormalities of the duodenum have been observed in non-ulcer dyspepsia . We aim ed to identify whether eosinophils in the upper gastrointestinal tract are a biomarker for non-ulcer dyspepsia . METHODS A r and om sample of an adult Swedish population ( n = 1001 ; mean age , 54 y ; 51 % female ) underwent upper endoscopy . Non-ulcer dyspepsia cases ( n = 51 , Rome II ) and r and omly selected controls ( n = 48 ) were identified . Two blinded independent observers assessed the gastroduodenal eosinophil counts . Eosinophils were quantified by counting the number per 5 high-power fields at each of 5 sites ( cardia , body , antrum , D1 duodenal bulb , and D2 second portion of duodenum ) , and total counts were summed over the 5 fields at each site . RESULTS The odds ratio for non-ulcer dyspepsia ( vs asymptomatic controls ) in subjects with high duodenal bulb eosinophil counts ( median , > /=22 , relative to < 22 ) was 11.7 ( 95 % confidence interval , 3.9 - 34.9 ) , adjusting for age , sex , and H pylori ; similar results were observed in D2 ( odds ratio = 7.3 ; 95 % confidence interval , 2.9 - 18.1 ) . A significant association with the number of eosinophil clusters was detected in the duodenum , with higher values in non-ulcer dyspepsia ( P < .01 ) . By immunostaining with major basic protein antibody in a subset of duodenal biopsy specimens , eosinophil degranulation was observed in non-ulcer dyspepsia ( 7 of 15 vs 0 of 5 controls ; P = .11 ) . Gastric eosinophil counts were overall not significantly increased in non-ulcer dyspepsia vs controls . Early satiety was associated with eosinophilia in D1 ( P = .01 ) and D2 ( P = .02 ) , adjusting for age , sex , and H pylori . CONCLUSIONS Duodenal eosinophilia may characterize a subset of adults with non-ulcer dyspepsia AIM To evaluate sertraline , a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia . METHODS Consecutive tertiary hospital patients with a clinical diagnosis of functional dyspepsia ( FD ) according to the Rome II criteria with a Hong Kong dyspepsia index ( HKDI ) of greater than 16 were recruited . Patients commenced enrolment prior to the inception of the Rome III criteria for functional dyspepsia . All patients were ethnic Chinese , had a normal upper endoscopy and were Helicobacter pylori negative prior to enrolment . Study patients were r and omized to receive sertraline 50 mg or placebo daily for 8 wk . HKDI symptom scores , quality of life , hospital anxiety and depression ( HAD ) scale and global symptom relief were evaluated before , during and after treatment . Adverse effects were monitored during and after treatment . RESULTS A total of 193 patients were r and omized in the intention to treat ( ITT ) , and 150 patients were included in the per protocol ( PP ) analysis . In both the ITT and PP , there was no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups at week 8 . In the ITT analysis , 98 and 95 patients were r and omized to the sertraline and placebo groups respectively . A total of 43 patients withdrew from the study ( 22.3 % ) by week 8 , with 23 of the 24 drop-outs in the sertraline group occurring prior to week 4 ( 95.8 % ) . In contrast , in the placebo arm , 11 of 19 patients dropped out by week 4 ( 57.9 % ) . Utilizing the last response carried forward to account for the drop-outs , there were no differences between the sertraline and placebo groups at baseline in terms of the HKDI , HKDI 26.08 ± 6.19 vs 26.70 ± 5.89 , P = 0.433 ; and at week 8 , HKDI 22.41 ± 6.36 vs 23.25 ± 7.30 , P = 0.352 respectively . In the PP analysis , 74 and 76 patients were r and omized to the sertraline and placebo groups respectively . At baseline , there were no statistically significant differences between the sertraline and placebo groups , HKDI 25.83 ± 6.313 vs 27.19 ± 5.929 respectively , P = 0.233 ; however by week 8 , patients in the sertraline group demonstrated a statistically significant difference in their Hong Kong Dyspepsia Index compared to placebo , HKDI 20.53 ± 6.917 vs 23.34 ± 7.199 , P = 0.02 , respectively ) . There was also no statistically significant difference in overall quality of life measures or the HAD scale related to treatment in either the ITT or PP analysis at week 8 . CONCLUSION This pilot study , the first to examine sertraline , a selective serotonin reuptake inhibitor , for the management of FD , did not find that it was superior to placebo BACKGROUND : Low-dose tricyclic antidepressants have been used to treat chronic somatic and gastrointestinal pain disorders , including refractory functional dyspepsia . However , there are only limited data on the effects of these drugs on upper gastrointestinal function . AIM : To compare the effects of two doses of amitriptyline ( AMT ) and placebo on gastric accommodation , emptying , satiation , and postpr and ial symptoms in healthy volunteers . METHODS : Using a parallel-group , double-blind , placebo-controlled design , 41 healthy volunteers were r and omized to AMT 25 mg , AMT 50 mg , or placebo for 2 wk . During the final 3 days of therapy , the following end points were assessed : fasting and postpr and ial gastric volumes , 2- and 4-h gastric emptying , time and volume to maximum satiation using a nutrient drink test , and postpr and ial symptoms 30 min later using 10-cm visual analog scales . AMT and metabolite levels were measured . RESULTS : AMT slowed gastric emptying at 2 h ( median 75 % for placebo , 57 % for AMT 25 mg , 67 % for AMT 50 mg ; P= 0.037 ) and 4 h ( median 98 % for placebo , 96 % for AMT 25 mg , 92 % for AMT 50 mg ; P= 0.003 ) . AMT did not affect gastric volumes or satiation volume , but it did reduce nausea scores at 30 min in a dose-dependent manner ( median 2.1 for placebo , 0.9 for AMT 25 mg , and 0.0 for AMT 50 mg ; P= 0.009 ) . CONCLUSION : In healthy volunteers , AMT slows gastric emptying of solids , but it does not significantly affect gastric volumes or satiation .  AMT reduces nausea after challenge with a high calorie liquid load Acute studies suggested a therapeutic benefit for fundus-relaxing drugs in functional dyspepsia ( FD ) with visceral hypersensitivity ( VH ) to gastric distention or impaired accommodation ( IA ) , but long-term studies are lacking . R-137696 is a serotonin-1A ( 5-HT(1A ) ) receptor agonist which relaxes the proximal stomach in man . Our aim was to investigate the influence of R-137696 on symptoms in FD with VH or IA . R and omized , double-blind , placebo-controlled , parallel group study of 4 weeks R-137696 2 mg t.i.d . in FD with VH or IA . Symptoms were assessed using the  patient assessment of upper gastrointestinal symptom severity index ( PAGI-SYM ) total score and individual symptom subscales . Barostat studies were performed before and after 4 weeks of treatment . Fifty-three patients ( 33 VH and 20 IA ) , 18 men , mean age 40 + /- 13 years were recruited . Twenty-four received placebo and 29 received R-137696 . In VH patients , both placebo and R-137696 improved total symptom scores , with a tendency for superiority of placebo ( -1.12 vs-0.51 , P = 0.07 ) . Placebo was superior for the subscales of early satiety , bloating , fullness and discomfort ( all P < 0.05 ) . In IA , both placebo and R-137696 had no significant influence on total or individual symptom scores ( -0.08 and -0.27 ) . In VH , both placebo and R-137696 increased the discomfort volume , without a statistical difference between both arms ( + 120 and + 164 mL ) . In IA , both placebo and R-137696 enhanced accommodation , without a statistical difference between both ( + 77 and + 159 mL ) . Adverse events were similar for drug and placebo . A 4-week administration of the fundus-relaxing 5-HT(1A ) agonist R-137696 failed to significantly improve symptoms , VH or gastric accommodation compared to placebo This guideline presents recommendations for the evaluation and management of patients with gastroparesis . Gastroparesis is identified in clinical practice through the recognition of the clinical symptoms and documentation of delayed gastric emptying . Symptoms from gastroparesis include nausea , vomiting , early satiety , postpr and ial fullness , bloating , and upper abdominal pain . Management of gastroparesis should include assessment and correction of nutritional state , relief of symptoms , improvement of gastric emptying and , in diabetics , glycemic control . Patient nutritional state should be managed by oral dietary modifications . If oral intake is not adequate , then enteral nutrition via jejunostomy tube needs to be considered . Parenteral nutrition is rarely required when hydration and nutritional state can not be maintained . Medical treatment entails use of prokinetic and antiemetic therapies . Current approved treatment options , including metoclopramide and gastric electrical stimulation ( GES , approved on a humanitarian device exemption ) , do not adequately address clinical need . Antiemetics have not been specifically tested in gastroparesis , but they may relieve nausea and vomiting . Other medications aim ed at symptom relief include unapproved medications or off-label indications , and include domperidone , erythromycin ( primarily over a short term ) , and central ly acting antidepressants used as symptom modulators . GES may relieve symptoms , including weekly vomiting frequency , and the need for nutritional supplementation , based on open-label studies . Second-line approaches include venting gastrostomy or feeding jejunostomy ; intrapyloric botulinum toxin injection was not effective in r and omized controlled trials . Most of these treatments are based on open-label treatment trials and small numbers . Partial gastrectomy and pyloroplasty should be used rarely , only in carefully selected patients . Attention should be given to the development of new effective therapies for symptomatic control Background and aims : Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain , suggesting the presence of hyperalgesia . It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations . In the former case , hyperalgesia should occur when intensity of non-painful sensations is still low . The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways . Methods : Forty eight consecutive dyspeptic patients ( 35 female ) underwent gastric sensitivity testing with a barostat balloon using a double r and om staircase protocol .  At the end of every distending step , patients scored perception of upper abdominal sensations on a graphic 0–6 rating scale and completed visual analogue scales ( VAS 0–100 mm ) for pain , nausea , satiety , and fullness . The end point was a rating scale of 5 or more . Results : Hypersensitivity was present in 20 patients ( 40 % ) ; gastric compliance did not differ between normo- and hypersensitive patients . At maximal distension ( score 5 or more ) , hypersensitive patients had significantly lower distending pressures and intra-balloon volumes , but similar VAS scores for pain , nausea , satiety , and fullness compared with normosensitive patients . In both normosensitive and hypersensitive patients , elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea , satiety , and fullness . Conclusions : Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures . Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations . These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity Objectives Levosulpiride is the levo-enantiomer of sulpiride , a well-known antiemetic , antidyspeptic and antipsychotic drug . This study was undertaken to investigate the effects of levosulpiride on dyspeptic symptoms and gastric motor function in a group of patients with functional dyspepsia showing delayed gastric emptying . Method Forty two eligible patients were entered into a 3 week , double-blind r and omized comparison of 25 mg of levosulpiride or placebo t.i.d .. Symptom assessment  and  gastric scintigraphy  following the intake of scrambled egg s and wich , were performed in each patient before and after treatment . Results The improvement of symptom score in levosulpiride group was higher than the placebo group ( p<0.05 ) . We assessed global efficacy , which was excellent in 1 ( 6 % ) , good 11 ( 65 % ) , fair 4 ( 24 % ) , nil 1 ( 6 % ) of those receiving levosulpiride , and fair 9(60 % ) , nil 5 ( 33 % ) , poor 1 ( 6 % ) of those receiving placebo . Levosulpiride tended to be more effective than placebo in relieving the dyspeptic symptoms especially in the subgroups of dysmotility-like ( p<0.05 ) and nonspecific ( p<0.05 ) as compared to other subgroups ( p=0.16 ) . The reduction of gastric emptying time after levosulpiride treatment was more marked than Placebo group ( p<0.05 ) . We found a significant correlation between changes of symptom score and gastric emptying time ( r=0.47 , p=0.01 . No serious adverse effects were reported after administration of either levosulpiride or placebo . Only two patients reported mild somnolence during levosulpiride administration . Conclusions Levosulpiride is effective and well tolerated in patients with functional dyspepsia accompanied by delayed gastric emptying .  Its efficacy may be related to its action on the gastric motor function by improving the delayed gastric emptying OBJECTIVES : Functional dyspepsia ( FD ) is a common condition in the general population ; however , its treatment remains a challenge . The aim of this study was to examine the efficacy of t and ospirone citrate , a new partial agonist of the 5-hydroxytryptamine 1A ( 5-HT1A ) receptor , in improving the symptoms of patients with FD . METHODS : In this double-blind , placebo-controlled , multicenter study , FD patients were r and omized to treatment with 10 mg t.i.d . t and ospirone citrate or to placebo for 4 weeks . The primary end point was change in abdominal symptom scores . The difference in the proportion of responders ( a total abdominal symptom score of 0 or 1 ) was also assessed . The quality -of-life question naire , the SF-8 , and a psychological test question naire , the State-Trait Anxiety Inventory ( STAI ) , were completed at baseline and at weekly intervals . RESULTS : Data were available for 144 patients : 73 for t and ospirone and 71 for placebo .  Improvements in total abdominal scores were significantly larger with t and ospirone than placebo at weeks 1 , 2 , and 4 . Significantly greater improvements in the t and ospirone group were observed in upper abdominal pain ( P=0.02 ) and discomfort ( P=0.002 ) at week 4 . The proportion of responders was significantly greater in the active treatment arm at weeks 3 ( P=0.017 ) and 4 ( P=0.0016 ) . Significant improvements in STAI ( P<0.0001 ) were reported in both arms , as well as in the majority of questions in the SF-8 ( P=0.04 ) . No serious adverse events were reported , with similar rates in both study arms . CONCLUSIONS : Despite a considerable placebo effect , the benefits of t and ospirone were shown in terms of improvement in abdominal symptom scores BACKGROUND & AIMS Functional gastrointestinal disorders ( FGID ) are common in the community . The natural history of FGID is unknown because of a lack of prospect i ve population -based studies and the indistinct nature of the phenotype . We sought to report the natural history of FGID in a US population . METHODS This prospect i ve cohort study used data from multiple vali date d surveys of r and om sample s of Olmsted County , MN , residents over a mean of a 12-year period between 1988 and 2003 ( n = 1365 ) . The surveys measured gastrointestinal symptoms experienced during the past year . Each subject received a minimum of 2 surveys . Point prevalence , onset , and disappearance rates and transition probabilities were calculated for individual FGIDs . RESULTS Between the initial and final surveys , the point prevalences ( per 100 residents ) were stable for irritable bowel syndrome ( 8.3 % and 11.4 % , respectively ) and functional dyspepsia ( 1.9 % and 3.3 % , respectively ) . The onset of each of the disorders studied was greater than the disappearance rate , but the transition probabilities varied across the different subgroups . Among people with symptoms at baseline , approximately 20 % had the same symptoms , 40 % had no symptoms , and 40 % had different symptoms at follow-up . CONCLUSIONS Although the prevalence of the FGID was stable over time , the turnover in symptom status was high . Many episodes of symptom disappearance were due to subjects changing symptoms rather than total symptom resolution . This transition between different FGIDs suggests a common etiopathogenesis Background : 50 % of patients with functional dyspepsia have delayed gastric emptying .  Levosulpiride is an orthopramide drug that stimulates gastrointestinal motility . Aim of our study was to evaluate the effect of levosulpiride on symptoms and gastric and gall‐bladder emptying , in dyspeptic patients BACKGROUND & AIMS Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects . Previous studies with these drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel syndrome . This study aim ed to assess the effectiveness of the serotonin and norepinephrine reuptake inhibitor venlafaxine in patients with functional dyspepsia . METHODS This was a multi-center , r and omized , double-blind , placebo-controlled trial . Participants had persistent dyspeptic symptoms and underwent upper gastrointestinal endoscopy in a secondary care hospital to exclude organic abnormalities . They were r and omly assigned to receive 8 weeks of treatment with either venlafaxine XR ( 2 weeks 75 mg once daily , 4 weeks 150 mg once daily , and 2 weeks 75 mg once daily ) or placebo .  Symptoms , health-related quality of life , anxiety , and depression were assessed before and at 4 , 8 , 12 , and 20 weeks after inclusion . RESULTS One hundred sixty patients were r and omized ; 56 % and 73 % of participants completed treatment with venlafaxine or placebo , respectively , according to protocol . There was no difference in proportions of symptom-free patients after 8 weeks of treatment or at 20 weeks after inclusion , with venlafaxine in comparison to placebo ( 37 % and 39 % , respectively ; odds ratio [ OR ] , 0.8 ; 95 % confidence interval [ CI ] , 0.3 - 2.1 ; and 42 % and 41 % , respectively ; OR , 3.1 ; 95 % CI , 0.9 - 12.6 ) . Per- protocol analysis did not reveal any differences between venlafaxine and placebo either ( 38 % and 39 % symptom-free , respectively ; OR , 1.0 ; 95 % CI , 0.4 - 2.4 at 8 weeks ) . CONCLUSIONS Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia Background : The role of 5‐hydroxytryptamine in the control of gastric fundus tone  in humans is still unknown . Selective 5‐hydroxytryptamine re‐uptake inhibitors act both central ly and peripherally to enhance the availability of physiologically released 5‐hydroxytryptamine Background : Functional dyspepsia ( FD ) is a common disorder but there is currently little efficacious drug therapy . Itopride , a prokinetic approved in several countries , showed promising efficacy in FD in a phase IIb trial . The aim of this study was to test the efficacy and safety of this drug in FD . Methods : Two similar placebo-controlled clinical trials were conducted ( International and North America ) . Males and females , 18–65 years old , with a diagnosis of FD ( Rome II ) and the absence ( by upper endoscopy ) of any relevant structural disease were recruited . All were negative for Helicobacter pylori and , if present , heartburn could not exceed one episode per week . Following screening , patients were r and omised to itopride 100 mg three times daily or identical placebo . The co- primary end points were : ( 1 ) global patient assessment ( GPA ) of efficacy ; and ( 2 ) Leeds Dyspepsia Question naire ( LDQ ) . Symptoms were evaluated at weeks 2 , 4 and 8 . Secondary measures of efficacy included Nepean Dyspepsia Index ( NDI ) quality of life . Results : The GPA responder rates at week 8 on itopride versus placebo were similar in both trials ( 45.2 % vs 45.6 % and 37.8 vs 35.4 % , respectively ; p = NS ) . A significant benefit of itopride over placebo was observed for the LDQ responders in the International ( 62 % vs 52.7 % , p = 0.04 ) but not the North American trial ( 46.9 % vs 44.8 % ) . The safety and tolerability profile were comparable with placebo , with the exception of prolactin elevations , which occurred more frequently on itopride ( 18/579 ) than placebo ( 1/591 ) . Conclusion : In this population with FD , itopride did not show a difference in symptom response from placebo BACKGROUND The efficacy of unselected monoamine reuptake inhibitors ( tricyclic antidepressants ) in the treatment of patients with functional gastrointestinal disorders ( FGD ) has not been convincingly demonstrated . We investigated the efficacy of an antidepressant ( mianserin ) with a different receptor profile ( combined 5-hydroxytryptamine-2 + 3 and alpha-2 antagonist ) in FGD . METHODS After excluding patients with psychopathology and initial placebo responders from the study , eligible patients ( n = 49 ) were r and omized to 7 weeks of double-blind treatment with either mianserin , 120 mg/day , or placebo . Efficacy was assessed by using observer-completed ratings , the Global Improvement Scale , and patient self-ratings , Visual Analog Scale , and Disability Scales . RESULTS Patients taking mianserin  reported less abdominal pain , symptoms of abdominal distress , and functional disability than those given placebo ( p < 0.001 ) . The efficacy was significant across different lengths of illness periods and types of functional disorder . There was no major change 4 weeks after tapering . CONCLUSION Mianserin may be an effective and well-tolerated pharmacologic short-term treatment for functional gastrointestinal disorders in patients with no clinical evidence of psychopathology BACKGROUND & AIMS Impaired accommodation and hypersensitivity to gastric distention are believed to be involved in the development of functional dyspepsia ( FD ) . Buspirone , a 5-hydroxytryptamine 1A receptor agonist , relaxes the proximal stomach in healthy individuals . We studied the effects of buspirone on symptoms and mechanisms of FD . METHODS We performed a r and omized , double-blind , placebo-controlled , crossover study of 17 patients ( 13 women ; mean age , 38.5 ± 2.4 years ) . The study included 2 treatment periods of 4 weeks each , separated by a 2-week washout period . In the first period , 7 participants were given buspirone ( 10 mg , 3 times daily for 4 weeks ) and 10 were given placebo 15 minutes before meals ; patients switched groups for the second period . We assessed meal-related symptoms and severity , along with gastric sensitivity , accommodation , and emptying ( by using barostat and breath tests ) before and after 4 weeks of treatment . RESULTS Buspirone significantly reduced the overall severity of symptoms of dyspepsia ( 7.5 ± 1.3 vs 11.5 ± 1.2 for placebo ; P < .005 ) and individual symptoms of postpr and ial fullness , early satiation , and upper abdominal bloating , whereas placebo had no significant effect ( all P < .05 ) . Buspirone did not alter the rate of gastric emptying of solids or sensitivity to gastric distention , but it significantly increased gastric accommodation , compared with placebo ( 229 ± 28 vs 141 ± 32 mL , respectively ; P < .05 ) , and delayed gastric emptying of liquids ( half-life = 64 ± 5 vs 119 ± 24 minutes , respectively ) . Adverse events were similar when patients were given buspirone or placebo . CONCLUSIONS In patients with FD , 4 weeks of administration of buspirone significantly improved symptoms and gastric accommodation , compared with placebo , whereas gastric emptying of liquids was delayed The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well‐established in patients with functional dyspepsia , but formal studies comparing different prokinetic drugs are lacking IMPORTANCE Many medications have anticholinergic effects . In general , anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy . However , a few studies suggest that anticholinergics may be associated with an increased risk for dementia . OBJECTIVE To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve population -based cohort study using data from the Adult Changes in Thought study in Group Health , an integrated health care delivery system in Seattle , Washington . We included 3434 participants 65 years or older with no dementia at study entry . Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003 . Beginning in 2004 , continuous replacement for deaths occurred . All participants were followed up every 2 years . Data through September 30 , 2012 , were included in these analyses . EXPOSURES Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure , which was defined as the total st and ardized daily doses ( TSDDs ) dispensed in the past 10 years . The most recent 12 months of use was excluded to avoid use related to prodromal symptoms . Cumulative exposure was up date d as participants were followed up over time . MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer disease using st and ard diagnostic criteria . Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics , health behaviors , and health status , including comorbidities . RESULTS The most common anticholinergic classes used were tricyclic antidepressants , first-generation antihistamines , and bladder antimuscarinics . During a mean follow-up of 7.3 years , 797 participants ( 23.2 % ) developed dementia ( 637 of these [ 79.9 % ] developed Alzheimer disease ) . A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease ( test for trend , P < .001 ) . For dementia , adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 ( 95 % CI , 0.74 - 1.16 ) for TSDDs of 1 to 90 ; 1.19 ( 95 % CI , 0.94 - 1.51 ) for TSDDs of 91 to 365 ; 1.23 ( 95 % CI , 0.94 - 1.62 ) for TSDDs of 366 to 1095 ; and 1.54 ( 95 % CI , 1.21 - 1.96 ) for TSDDs greater than 1095 . A similar pattern of results was noted for Alzheimer disease . Results were robust in secondary , sensitivity , and post hoc analyses . CONCLUSIONS AND RELEVANCE Higher cumulative anticholinergic use is associated with an increased risk for dementia . Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time Aliment Pharmacol Ther 2011 ; 33 : 395–402 BACKGROUND & AIMS Antidepressants are frequently prescribed to treat functional dyspepsia ( FD ) , a common disorder characterized by upper abdominal symptoms , including discomfort or postpr and ial fullness . However , there is little evidence of the efficacy of these drugs in patients with FD . We performed a r and omized , double-blind , placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms , gastric emptying ( GE ) , and meal-induced satiety in patients with FD . METHODS We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants . Patients ( n = 292 ; 44 ± 15 years old , 75 % were female , 70 % with dysmotility-like FD , and 30 % with ulcer-like FD ) were r and omly assigned to groups given placebo , 50 mg amitriptyline , or 10 mg escitalopram for 10 weeks . The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks ( of 12 ) . Secondary end points included GE time , maximum tolerated volume in Nutrient Drink Test , and FD-related quality of life . RESULTS An adequate relief response was reported by 39 subjects given placebo ( 40 % ) , 51 given amitriptyline ( 53 % ) , and 37 given escitalopram ( 38 % ) ( P = .05 , after treatment , adjusted for baseline balancing factors including all subjects ) . Subjects with ulcer-like FD given amitriptyline were > 3-fold more likely to report adequate relief than those given placebo ( odds ratio = 3.1 ; 95 % confidence interval : 1.1 - 9.0 ) . Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group . Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE ( odds ratio = 0.4 ; 95 % confidence interval : 0.2 - 0.8 ) . Both antidepressants improved overall quality of life . CONCLUSIONS Amitriptyline , but not escitalopram , appears to benefit some patients with FD , particularly those with ulcer-like ( painful ) FD . Patients with delayed GE do not respond to these drugs . Clinical Trials.gov ID : NCT00248651
target: However , benefit was limited to antipsychotics and tricyclic antidepressants .
  Conclusions Psychotropic drugs may be an effective treatment for FD , but the effect appears to be limited to antipsychotics and tricyclic antidepressants with fewer trials for other agents , meaning that firm conclusions for efficacy can not be made .
background: Objective Functional dyspepsia ( FD ) is a chronic gastroduodenal disorder .
  Individuals with FD demonstrate visceral hypersensitivity , abnormal central pain processing , and low mood , but it is unclear whether psychotropic drugs are an effective treatment for the condition .