AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period...AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.展开更多
AIM:To compare the efficacy and side effects of lowdose amitriptyline(AMT)with proton pump inhibitor treatment in patients with globus pharyngeus.METHODS:Thirty-four patients who fulfilled the RomeⅢcriteria for funct...AIM:To compare the efficacy and side effects of lowdose amitriptyline(AMT)with proton pump inhibitor treatment in patients with globus pharyngeus.METHODS:Thirty-four patients who fulfilled the RomeⅢcriteria for functional esophageal disorders were included in this study.Patients were randomly assigned to receive either 25 mg AMT before bedtime(AMT group)or 40 mg Pantoprazole once daily for 4 wk(conventional group).The main efficacy endpoint was assessed using the Glasgow Edinburgh Throat Scale(GETS).The secondary efficacy endpoints included the Medical Outcomes Study 36-item short form health survey[social functioning(SF)-36]and the Pittsburgh Sleep Quality Index.Treatment response was defined as a>50%reduction in GETS scores.All patients entering this study recorded side effects at days 1,8,15,22 and 29 using a visual analogue scale.RESULTS:Thirty patients completed the study.After 4 wk of treatment,the AMT group had a greater response than the conventional group(75%vs 35.7%,P=0.004).At day 3,the AMT group showed significantly more improvement than the Conventional group in GETS score(3.69±1.14 vs 5.64±1.28,P=0.000).After 4 wk of treatment,the AMT group showed significantly greater improvement in GETS score and sleep quality than the Conventional group(1.25±1.84 vs 3.79±2.33,4.19±2.07 vs 8.5±4.97;P<0.01 for both).Additionally,the AMT group was more likely than the Conventional group to experience improvement in the SF-36,including general health,vitality,social functioning and mental health(P=0.044,0.024,0.049 and 0.005).Dry mouth,sleepiness,dizziness and constipation were the most common side effects.CONCLUSION:Low-dose AMT is well tolerated and can significantly improve patient symptoms,sleep and quality of life.Thus,low-dose AMT may be an effective treatment for globus pharyngeus.展开更多
AIM:To investigate the efficacy of amitriptyline with proton pump inhibitor(PPI)for the treatment of functional chest pain(FCP).METHODS:This was a randomized,open-label trial investigating the addition of low dose ami...AIM:To investigate the efficacy of amitriptyline with proton pump inhibitor(PPI)for the treatment of functional chest pain(FCP).METHODS:This was a randomized,open-label trial investigating the addition of low dose amitriptyline(10 mg at bedtime)to a conventional dose of rabeprazole(20 mg/d)(group A,n = 20)vs a double-dose of rabeprazole(20 mg twice daily)(group B,n = 20)for patients with FCP whose symptoms were refractory to PPI.The primary efficacy endpoints were assessed by global symptom score assessment and the total number of individuals with > 50% improvement in their symptom score.RESULTS:The between-group difference in global symptom scores was statistically significant during the last week of treatment(overall mean difference;3.75 ± 0.31 vs 4.35 ± 0.29,the between-group difference;P < 0.001).Furthermore,70.6% of patients in group A had their symptoms improve by > 50%,whereas only 26.3% of patients in group B had a similar treatment response(70.6% vs 26.3%,P = 0.008).Specifically,patients in group A had a significantly greater improvement in the domains of body pain and general health perception than did patients in group B(52.37 ± 17.00 vs 41.32 ± 12.34,P = 0.031 and 47.95 ± 18.58 vs 31.84 ± 16.84,P = 0.01,respectively).CONCLUSION:Adding amitriptyline to a PPI was more effective than a double-dose of PPI in patients with FCP refractory to a conventional dose of PPI.展开更多
In this study platelet 3H-paroxetine binding site was studied in 16 depressed pa-tients and 16 healthy volunteers. We found that the mean Bmax of 3H-paroxetine binding on theplatelets of depressed patients was signifi...In this study platelet 3H-paroxetine binding site was studied in 16 depressed pa-tients and 16 healthy volunteers. We found that the mean Bmax of 3H-paroxetine binding on theplatelets of depressed patients was significantly lower than that of normal controls. After treated withamitriptyline or electro-acupuncture for 6 weeks, the density of paroxetine binding sites increased to-wards normal in well responded patients. But no significant difference was found between electro-acupuncture and amitriptyline as compared in their effects on 3H-paroxetine binding sites.展开更多
AIM: To study the effects of low dose amitriptyline on cardiac conduction in children.METHODS: Secondary analysis of data obtained from a double-blind, randomized placebo-controlled trial, evaluating low dose amitript...AIM: To study the effects of low dose amitriptyline on cardiac conduction in children.METHODS: Secondary analysis of data obtained from a double-blind, randomized placebo-controlled trial, evaluating low dose amitriptyline in children with a diagnosis of functional abdominal pain, functional dyspepsia, and irritable bowel syndrome according to the Rome II criteria. Children 8-17 years of age were recruited from the pediatric gastroenterology clinics of 6 tertiary care centers in the United States. The electrocardiograms(EKGs) done prior to initiation of amitrityline and 1 mo after initiation of amitriptyline were examined. The changes in cardiac conduction were evaluated in patients and controls. RESULTS: Thirty children were included in the study. There were 12 patients, ages 9-17 years of both genders, in the amitriptyline treatment group and 18 patients, ages 9-17 years of both genders, in the placebotreatment group. None of the patients had any baseline EKG abnormality. Amitriptyline use was associated with an increase in heart rate(P = 0.024) and QTc interval(P = 0.0107) as compared to pre-EKGs. Children in the placebo group were also noted to present a statistically significant increase in QTc interval(P = 0.0498). None of the patients developed borderline QTc prolongation or long-QT syndrome after they were started on amitriptyline.CONCLUSION: The study findings suggest that once patients with functional gastrointestinal disorders have been screened for prolonged QTc interval on baseline EKG, they probably do not need a second EKG for reevaluation of cardiac conduction after starting low dose amitriptyline.展开更多
A new and simple procedure for the spectrophotometric determination of the tricyclic antidepressant drug amitriptyline is proposed. The method is based on enhancement of sensitivity of the [AMIYTP]+ β-cyclodextrin an...A new and simple procedure for the spectrophotometric determination of the tricyclic antidepressant drug amitriptyline is proposed. The method is based on enhancement of sensitivity of the [AMIYTP]+ β-cyclodextrin and PEG molecules involved in formation of molecules inclusion complex, in presence of polyethylene glycol (PEG) medium. The mole ratio of [AMIYTP]+ β-cyclodextrin and PEG molecules in inclusion complex were determined by the curve fitting method. The value of molar absorptivity of {[AMIYTP: (β CD)] PEG} complex in term of the drug lies in rage of (2.20 - 2.23) × 104 L·mole–1·cm–1 at absorption maximum 242 nm. The slope, intercept and correlation co-efficient were found to be 14.21, 0.0046, and 0.998, respectively. The effect of analytical variables on the determination of the drug and composition of the ion associated complex are discussed in the paper. This method is applicable in the determina-tion of amitriptyline in the pharmaceutical preparations.展开更多
Diabetic neuropathies are a family of nerve disorders caused by diabetes.Symptoms of the disease include nerve palsy,mononeuropathy,mononeuropathy multiplex,diabetic amyotrophy,painful polyneuropathy,autonomic neuropa...Diabetic neuropathies are a family of nerve disorders caused by diabetes.Symptoms of the disease include nerve palsy,mononeuropathy,mononeuropathy multiplex,diabetic amyotrophy,painful polyneuropathy,autonomic neuropathy,and thoracoabdominal neuropathy.In this study,type 2 diabetes in rats was induced with nicotinamidestreptozotocin.Drug treatment was initiated on the d 15,with the combination regimen of metformin,pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin,amitriptyline and sitagliptin and led to significantly improved glycemic control,increased grip strength and paw jumping response on d 21,28 and 35(P < 0.001).Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21,28 and 35(P < 0.001).Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells,while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain.In conclusion,treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain,but causes an increase in grip strength and pain sensitivity,exhibits neural protection,and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.展开更多
Available pharmacotherapies for autism spectrum disorders(ASD)are reviewed based on clinical and research experience,highlighting some older drugs with emerging evidence.Several medications show efficacy in ASD,though...Available pharmacotherapies for autism spectrum disorders(ASD)are reviewed based on clinical and research experience,highlighting some older drugs with emerging evidence.Several medications show efficacy in ASD,though controlled studies in ASD are largely lacking.Only risperidone and aripiprazole have Federal Drug Administration approval in the United States.Methylphenidate(MPH)studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder(ADHD)than in the typically developing(TD)population;atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes.Guanfacine improved hyperactivity in ASD comparably to TD.Dextroamphetamine promises greater efficacy than MPH in ASD.ADHD medications reduce impulsive aggression in youth,and may also be key for this in adults.Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors.Trials of antiseizure medications in ASD remain inconclusive,however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors.No identified drugs treat ASD core symptoms;oxytocin lacked efficacy.Amitriptyline and loxapine however,show promise.Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies,but may be weight-sparing.Amitriptyline at approximately 1 mg/kg/day used cautiously,shows efficacy for sleep,anxiety,impulsivity and ADHD,repetitive behaviors,and enuresis.Both drugs have promising neurotrophic properties.展开更多
文摘AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.
文摘AIM:To compare the efficacy and side effects of lowdose amitriptyline(AMT)with proton pump inhibitor treatment in patients with globus pharyngeus.METHODS:Thirty-four patients who fulfilled the RomeⅢcriteria for functional esophageal disorders were included in this study.Patients were randomly assigned to receive either 25 mg AMT before bedtime(AMT group)or 40 mg Pantoprazole once daily for 4 wk(conventional group).The main efficacy endpoint was assessed using the Glasgow Edinburgh Throat Scale(GETS).The secondary efficacy endpoints included the Medical Outcomes Study 36-item short form health survey[social functioning(SF)-36]and the Pittsburgh Sleep Quality Index.Treatment response was defined as a>50%reduction in GETS scores.All patients entering this study recorded side effects at days 1,8,15,22 and 29 using a visual analogue scale.RESULTS:Thirty patients completed the study.After 4 wk of treatment,the AMT group had a greater response than the conventional group(75%vs 35.7%,P=0.004).At day 3,the AMT group showed significantly more improvement than the Conventional group in GETS score(3.69±1.14 vs 5.64±1.28,P=0.000).After 4 wk of treatment,the AMT group showed significantly greater improvement in GETS score and sleep quality than the Conventional group(1.25±1.84 vs 3.79±2.33,4.19±2.07 vs 8.5±4.97;P<0.01 for both).Additionally,the AMT group was more likely than the Conventional group to experience improvement in the SF-36,including general health,vitality,social functioning and mental health(P=0.044,0.024,0.049 and 0.005).Dry mouth,sleepiness,dizziness and constipation were the most common side effects.CONCLUSION:Low-dose AMT is well tolerated and can significantly improve patient symptoms,sleep and quality of life.Thus,low-dose AMT may be an effective treatment for globus pharyngeus.
文摘AIM:To investigate the efficacy of amitriptyline with proton pump inhibitor(PPI)for the treatment of functional chest pain(FCP).METHODS:This was a randomized,open-label trial investigating the addition of low dose amitriptyline(10 mg at bedtime)to a conventional dose of rabeprazole(20 mg/d)(group A,n = 20)vs a double-dose of rabeprazole(20 mg twice daily)(group B,n = 20)for patients with FCP whose symptoms were refractory to PPI.The primary efficacy endpoints were assessed by global symptom score assessment and the total number of individuals with > 50% improvement in their symptom score.RESULTS:The between-group difference in global symptom scores was statistically significant during the last week of treatment(overall mean difference;3.75 ± 0.31 vs 4.35 ± 0.29,the between-group difference;P < 0.001).Furthermore,70.6% of patients in group A had their symptoms improve by > 50%,whereas only 26.3% of patients in group B had a similar treatment response(70.6% vs 26.3%,P = 0.008).Specifically,patients in group A had a significantly greater improvement in the domains of body pain and general health perception than did patients in group B(52.37 ± 17.00 vs 41.32 ± 12.34,P = 0.031 and 47.95 ± 18.58 vs 31.84 ± 16.84,P = 0.01,respectively).CONCLUSION:Adding amitriptyline to a PPI was more effective than a double-dose of PPI in patients with FCP refractory to a conventional dose of PPI.
文摘In this study platelet 3H-paroxetine binding site was studied in 16 depressed pa-tients and 16 healthy volunteers. We found that the mean Bmax of 3H-paroxetine binding on theplatelets of depressed patients was significantly lower than that of normal controls. After treated withamitriptyline or electro-acupuncture for 6 weeks, the density of paroxetine binding sites increased to-wards normal in well responded patients. But no significant difference was found between electro-acupuncture and amitriptyline as compared in their effects on 3H-paroxetine binding sites.
文摘AIM: To study the effects of low dose amitriptyline on cardiac conduction in children.METHODS: Secondary analysis of data obtained from a double-blind, randomized placebo-controlled trial, evaluating low dose amitriptyline in children with a diagnosis of functional abdominal pain, functional dyspepsia, and irritable bowel syndrome according to the Rome II criteria. Children 8-17 years of age were recruited from the pediatric gastroenterology clinics of 6 tertiary care centers in the United States. The electrocardiograms(EKGs) done prior to initiation of amitrityline and 1 mo after initiation of amitriptyline were examined. The changes in cardiac conduction were evaluated in patients and controls. RESULTS: Thirty children were included in the study. There were 12 patients, ages 9-17 years of both genders, in the amitriptyline treatment group and 18 patients, ages 9-17 years of both genders, in the placebotreatment group. None of the patients had any baseline EKG abnormality. Amitriptyline use was associated with an increase in heart rate(P = 0.024) and QTc interval(P = 0.0107) as compared to pre-EKGs. Children in the placebo group were also noted to present a statistically significant increase in QTc interval(P = 0.0498). None of the patients developed borderline QTc prolongation or long-QT syndrome after they were started on amitriptyline.CONCLUSION: The study findings suggest that once patients with functional gastrointestinal disorders have been screened for prolonged QTc interval on baseline EKG, they probably do not need a second EKG for reevaluation of cardiac conduction after starting low dose amitriptyline.
文摘A new and simple procedure for the spectrophotometric determination of the tricyclic antidepressant drug amitriptyline is proposed. The method is based on enhancement of sensitivity of the [AMIYTP]+ β-cyclodextrin and PEG molecules involved in formation of molecules inclusion complex, in presence of polyethylene glycol (PEG) medium. The mole ratio of [AMIYTP]+ β-cyclodextrin and PEG molecules in inclusion complex were determined by the curve fitting method. The value of molar absorptivity of {[AMIYTP: (β CD)] PEG} complex in term of the drug lies in rage of (2.20 - 2.23) × 104 L·mole–1·cm–1 at absorption maximum 242 nm. The slope, intercept and correlation co-efficient were found to be 14.21, 0.0046, and 0.998, respectively. The effect of analytical variables on the determination of the drug and composition of the ion associated complex are discussed in the paper. This method is applicable in the determina-tion of amitriptyline in the pharmaceutical preparations.
文摘Diabetic neuropathies are a family of nerve disorders caused by diabetes.Symptoms of the disease include nerve palsy,mononeuropathy,mononeuropathy multiplex,diabetic amyotrophy,painful polyneuropathy,autonomic neuropathy,and thoracoabdominal neuropathy.In this study,type 2 diabetes in rats was induced with nicotinamidestreptozotocin.Drug treatment was initiated on the d 15,with the combination regimen of metformin,pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin,amitriptyline and sitagliptin and led to significantly improved glycemic control,increased grip strength and paw jumping response on d 21,28 and 35(P < 0.001).Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21,28 and 35(P < 0.001).Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells,while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain.In conclusion,treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain,but causes an increase in grip strength and pain sensitivity,exhibits neural protection,and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.
文摘Available pharmacotherapies for autism spectrum disorders(ASD)are reviewed based on clinical and research experience,highlighting some older drugs with emerging evidence.Several medications show efficacy in ASD,though controlled studies in ASD are largely lacking.Only risperidone and aripiprazole have Federal Drug Administration approval in the United States.Methylphenidate(MPH)studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder(ADHD)than in the typically developing(TD)population;atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes.Guanfacine improved hyperactivity in ASD comparably to TD.Dextroamphetamine promises greater efficacy than MPH in ASD.ADHD medications reduce impulsive aggression in youth,and may also be key for this in adults.Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors.Trials of antiseizure medications in ASD remain inconclusive,however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors.No identified drugs treat ASD core symptoms;oxytocin lacked efficacy.Amitriptyline and loxapine however,show promise.Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies,but may be weight-sparing.Amitriptyline at approximately 1 mg/kg/day used cautiously,shows efficacy for sleep,anxiety,impulsivity and ADHD,repetitive behaviors,and enuresis.Both drugs have promising neurotrophic properties.
