Attention Deficit/Hyperactivity Disorder (ADHD) is characterised by developmentally inappropriate levels of inattention, impulsivity and hyperactivity. As might be expected of a disorder in which inhibitory deficits f...Attention Deficit/Hyperactivity Disorder (ADHD) is characterised by developmentally inappropriate levels of inattention, impulsivity and hyperactivity. As might be expected of a disorder in which inhibitory deficits form part of the diagnostic criteria, deficits in response inhibition in ADHD have been evidenced in a number of studies. To date, the tasks used in such studies have required participants to inhibit the learned stimulus-response associations that result in unwanted behavior. However, no research has examined the inhibition of stimulus-stimulus associations, formally ‘conditioned inhibition’. The present study used video game style conditioned inhibition procedures, developed for children and adolescents with a clinical diagnosis of ADHD and suitable for typically developing matched controls. Two computer-based tasks (‘Mission to Mars’ and ‘Weapon-X’) required participants to predict the occurrence of an outcome based on the stimuli presented. We selected 12 male participants with ADHD on medication (methylphenidate), but without comorbid Tourette Syndrome, pervasive developmental disorder, learning disability or psychosis. This group showed overall normal inhibition of stimulus-stimulus associations, measured repeatedly over trials and with two task variants. There was no correlation between inhibitory learning and symptom severity ratings. However, participants with ADHD on higher dosages of methylphenidate, or longer duration of treatment with methylphenidate, showed improved ability to anticipate outcomes following the different stimulus presentations on non-inhibited versus inhibited trials. This effect was most clearly demonstrated on the Weapon-X task. Thus, methylphenidate doserelatedly improved the expression of associative learning. This action may contribute to its therapeutic effects in improving cognitive function in ADHD.展开更多
Methylphenidate （MPH） is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder （ADHD）. Although several studies have evaluated the effects of MPH on human brain act...Methylphenidate （MPH） is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder （ADHD）. Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging （fMRI）, few studies have focused on spontaneous brain activity. In the current study, we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18 normal adult males. A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication, and a resting-state fMRI scan was obtained 1 h after medication （20 mg MPH or placebo, order counterbalanced between participants）. We demonstrated that： （1） there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; （2） the left middle and superior temporal gyri had stronger MPH-related regional homogeneity （ReHo）; and （3） the left lingual gyrus had weaker MPH-related ReHo. Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults, even though there are no behavioral differences. This method can be applied to patients with mental illness who may be treated with MPH, and be used to compare the difference between patients taking MPH and normal participants, to help reveal the mechanism of how MPH works.展开更多
This study retrospectively analyzed the medication prescriptions of children diagnosed with attention-deficit/hyperactivity disorder(ADHD) in Ningbo Psychiatric Hospital and Ningbo Women and Children’s Hospital from ...This study retrospectively analyzed the medication prescriptions of children diagnosed with attention-deficit/hyperactivity disorder(ADHD) in Ningbo Psychiatric Hospital and Ningbo Women and Children’s Hospital from March 2018 to September 2020 and compared the drug retention rate of methylphenidate hydrochloride and atomoxetine hydrochloride. The prescription automatic screening system was used to screen the prescriptions in children with ADHD. Kaplan-Meier regression analysis was used to compare prescription retention rates between the two regimens after adjusting for gender, age, body weight, and prescription cost. The mean age of the methylphenidate hydrochloride group was 8.75 ± 2.16 years, and the monthly prescription cost was 327.37 ± 146.64 RMB. The average age of the atomoxetine group was 8.33 ± 1.73 years, and the monthly prescription cost was 363.15 ± 154.90 ￥. There were some differences in the age of enrollment and the monthly prescription cost between the two regimens(all P < 0.01). Moreover, the retention rate of methylphenidate hydrochloride was higher compared with atomoxetine hydrochloride within 18 months. Kaplan-Meier regression analysis showed that this trend was significant(Tarone-ware, Chi-square value = 14.893, P < 0.001). Prescription costs might be a factor affecting drug retention. This study found that the retention rates were decreased month by month in children with ADHD, and after 5 months, the retention rates were 52.20% and 41.22%, respectively, far below the recommended levels of the guidelines.展开更多
The objective of this study was to examine whether stimulants impact pubertal development in adolescent Attention Deficit Hyperactivity Disorder (ADHD), an understudied subject. Pubertal staging data were collected du...The objective of this study was to examine whether stimulants impact pubertal development in adolescent Attention Deficit Hyperactivity Disorder (ADHD), an understudied subject. Pubertal staging data were collected during a 2-year open study of extended release methylphenidate in adolescents (N = 111) with ADHD. Tanner stages were compared to national estimates. The sample was primarily male, Caucasian, and a mean age of 14.8 years at baseline. The baseline Tanner stage for 70% of subjects was consistent with chronological age. For the majority of subjects who reached 12 - 20 months (N = 25) or 24 months (N = 21) endpoints, the Tanner stage at respective endpoints was consistent with age. We found that progression in Tanner stage was not associated with OROS MPH duration or dose (p > 0.10). Long-term treatment with extended release methylphenidate did not appear to adversely impact pubertal development in this sample of adolescents with ADHD.展开更多
Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical...Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40°C/75% RH and 18 Months at 25°C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.展开更多
Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration(FDA) recommends the proper disposal of unused prescribed ...Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration(FDA) recommends the proper disposal of unused prescribed medications to maintain safety and prevent environmental hazards. However, many of the current disposal techniques do not properly address safety. A drug disposal pouch containing granular activated carbon offers a unique disposal method to deactivate residual or expired medication in a convenient, effective, and safe manner. A robust and validated method for methylphenidate hydrochloride and loxapine succinate was developed using high-performance liquid chromatography(HPLC) and the deactivation efficiency of the disposal system was tested. Methylphenidate hydrochloride was analyzed on a C18 analytical column(250 mm ?4.60 mm, 100?) using acetonitrile-water(0.05%(v/v) trifluoroacetic acid) as the mobile phase at a flow rate of1.0 mL/min with a run time of 15 min and retention time of 7.8 min. Loxapine succinate was separated on a C8100?(250 mm ? 4.6 mm, 5 mm) column maintained at 25 °C using a flow rate of 1.0 mL/min. The run time was 10 min and the retention time of the drug was around 4.6 min. Mobile phase was composed of acetonitrile and water(0.3% triethylamine) at pH 3.0 as 40:60(v/v). Reference standard solutions(100 mg/mL) for both drugs were prepared by dissolving in mobile phases. These methods provide good linearity(R2? 0.999) over the range of 5–100 mg/mL for methylphenidate hydrochloride and 0.1–100 mg/mL for loxapine succinate. The assay methods were successfully applied to study the deactivation of these drugs.展开更多
Objectives: This paper deals with the methylphenidate (MPH) misuse by adults in Germany. Results of a survey among primary care physicians/internists have been supplemented by a comparison with the literature. Methods...Objectives: This paper deals with the methylphenidate (MPH) misuse by adults in Germany. Results of a survey among primary care physicians/internists have been supplemented by a comparison with the literature. Methods: In the period from October 5-20, 2015, a survey was sent to 414 primary care physicians/internists in four German cities (n = 10 were undeliverable). The response rate was 58% (n = 235). 34 original works on MPH abuse worldwide were found in the literature and are used in the analysis of the present data situation. The literature published before November 9, 2015 is considered in this paper. Results: 14% of the doctors who took part in the survey said that they had been asked for MPH prescriptions without any medical indication. The most frequent reason given for the request (42%) was adult attention deficit/hyperactivity disorder (ADHD) not verified by documents. According to the comparison with the literature, university students had a lifetime prevalence of MPH misuse ranging from 0.8% to 16.6% and school children had a misuse rate of 4.0%. In the civilian US population, the misuse rate was 4.2%. Among patients in possession of a current MPH prescription due to a diagnosis, the lifetime prevalence was 29% and among adolescents with suspected alcohol and/or drug problems 20%. Conclusions: MPH misuse is a major problem which has not been studied sufficiently. MPH misuse not only plays a role in the field of psychiatry, but also in other disciplines. Misuse particularly following a therapeutic prescription should be taken into account.展开更多
Operant conditioning of the electroencephalographic rhythm (EEG biofeedback) is argued to be an effective method for treating children with ADHD. This study was designed to evaluate whether this method, compared to me...Operant conditioning of the electroencephalographic rhythm (EEG biofeedback) is argued to be an effective method for treating children with ADHD. This study was designed to evaluate whether this method, compared to methylphenidate, achieves an equally effective outcome. Participants were 39 children aged between 7-12 years. Thirteen children with attention-deficit/hyperactivity disorder (ADHD) were trained to enhance the amplitude of the beta1 activity (15-18 Hz) and decrease the amplitude of the theta activity (4-8 Hz), and 13 of which were treated with methylphenidate alone. Thirteen healthy children did not receive intervention. Several behavioral, neuropsychological and experimental tests were administered before and after intervention. While behavioral measures were improved by both types of method, methylphenidate was significantly more effective than EEG biofeedback. Response inhibition was improved only by EEG biofeedback. Both EEG biofeedback and methylphenidate were associated with improvements on the variability and accuracy measures of computerized tests. Intellectual ability increased also by both methods. Although averaged effect size for methylphenidate seems to be greater than for EEG biofeedback, the difference was not significant. In conjunction with other studies, these findings demonstrate that EEG biofeedback can significantly improve several be-havioral and cognitive functions in children with ADHD, and it might be an alternative treatment for non-responders or incomplete responders to medication as well as for those their parents favor a non-pharmacological treatment.展开更多
文摘目的对比哌甲酯与托莫西汀治疗儿童注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)的效果及对皮质酮(corticosterone,CORT)、25-羟维生素D[25-hydroxyvitamin D,25-(OH)D]水平的影响。方法选择2023年1月至2024年6月我院接受治疗的ADHD患儿,以简单排序随机法分为试验组(n=53,托莫西汀治疗)和对照组(n=53,哌甲酯治疗)。试验组中途退出研究2例,对照组中途退出研究3例。比较两组临床疗效、CORT、25-(OH)D、视听整合持续操作测验(integrated visual and auditorycontinuous performance test,IVA-CPT)、中国修订韦氏儿童智力量表(Chinese revision of the wechsler intelligence scale for children,C-WISC)评分及不良反应发生率等。结果治疗后,两组总有效率差异显著(92.16%vs.72.00%,P<0.05)。两组患儿CORT、25-(OH)D评分均较治疗前升高(P<0.05),且试验组高于对照组(P<0.05)。试验组听觉反应控制商数、视觉反应控制商数、C-WISC评分高于对照组(P<0.05)。两组SNAP-IV评分、多动指数、临床疗效总评量表均较治疗前降低(P<0.05),且试验组低于对照组(P<0.05)。试验组和对照组不良反应发生情况无显著差异(3.92%vs.10.00%,P>0.05)。结论托莫西汀较哌甲酯治疗ADHD患儿有更好的疗效,可改善CORT、25-(OH)D水平。
文摘Attention Deficit/Hyperactivity Disorder (ADHD) is characterised by developmentally inappropriate levels of inattention, impulsivity and hyperactivity. As might be expected of a disorder in which inhibitory deficits form part of the diagnostic criteria, deficits in response inhibition in ADHD have been evidenced in a number of studies. To date, the tasks used in such studies have required participants to inhibit the learned stimulus-response associations that result in unwanted behavior. However, no research has examined the inhibition of stimulus-stimulus associations, formally ‘conditioned inhibition’. The present study used video game style conditioned inhibition procedures, developed for children and adolescents with a clinical diagnosis of ADHD and suitable for typically developing matched controls. Two computer-based tasks (‘Mission to Mars’ and ‘Weapon-X’) required participants to predict the occurrence of an outcome based on the stimuli presented. We selected 12 male participants with ADHD on medication (methylphenidate), but without comorbid Tourette Syndrome, pervasive developmental disorder, learning disability or psychosis. This group showed overall normal inhibition of stimulus-stimulus associations, measured repeatedly over trials and with two task variants. There was no correlation between inhibitory learning and symptom severity ratings. However, participants with ADHD on higher dosages of methylphenidate, or longer duration of treatment with methylphenidate, showed improved ability to anticipate outcomes following the different stimulus presentations on non-inhibited versus inhibited trials. This effect was most clearly demonstrated on the Weapon-X task. Thus, methylphenidate doserelatedly improved the expression of associative learning. This action may contribute to its therapeutic effects in improving cognitive function in ADHD.
基金supported by the National Natural Science Foundation of China(30600181)a Key Project of the Department of Science and Technology of Zhejiang Province,China(2006C23030)
文摘Methylphenidate （MPH） is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder （ADHD）. Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging （fMRI）, few studies have focused on spontaneous brain activity. In the current study, we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18 normal adult males. A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication, and a resting-state fMRI scan was obtained 1 h after medication （20 mg MPH or placebo, order counterbalanced between participants）. We demonstrated that： （1） there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; （2） the left middle and superior temporal gyri had stronger MPH-related regional homogeneity （ReHo）; and （3） the left lingual gyrus had weaker MPH-related ReHo. Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults, even though there are no behavioral differences. This method can be applied to patients with mental illness who may be treated with MPH, and be used to compare the difference between patients taking MPH and normal participants, to help reveal the mechanism of how MPH works.
基金Natural Science Foundation of Ningbo(Grant No.2018A610245)。
文摘This study retrospectively analyzed the medication prescriptions of children diagnosed with attention-deficit/hyperactivity disorder(ADHD) in Ningbo Psychiatric Hospital and Ningbo Women and Children’s Hospital from March 2018 to September 2020 and compared the drug retention rate of methylphenidate hydrochloride and atomoxetine hydrochloride. The prescription automatic screening system was used to screen the prescriptions in children with ADHD. Kaplan-Meier regression analysis was used to compare prescription retention rates between the two regimens after adjusting for gender, age, body weight, and prescription cost. The mean age of the methylphenidate hydrochloride group was 8.75 ± 2.16 years, and the monthly prescription cost was 327.37 ± 146.64 RMB. The average age of the atomoxetine group was 8.33 ± 1.73 years, and the monthly prescription cost was 363.15 ± 154.90 ￥. There were some differences in the age of enrollment and the monthly prescription cost between the two regimens(all P < 0.01). Moreover, the retention rate of methylphenidate hydrochloride was higher compared with atomoxetine hydrochloride within 18 months. Kaplan-Meier regression analysis showed that this trend was significant(Tarone-ware, Chi-square value = 14.893, P < 0.001). Prescription costs might be a factor affecting drug retention. This study found that the retention rates were decreased month by month in children with ADHD, and after 5 months, the retention rates were 52.20% and 41.22%, respectively, far below the recommended levels of the guidelines.
文摘The objective of this study was to examine whether stimulants impact pubertal development in adolescent Attention Deficit Hyperactivity Disorder (ADHD), an understudied subject. Pubertal staging data were collected during a 2-year open study of extended release methylphenidate in adolescents (N = 111) with ADHD. Tanner stages were compared to national estimates. The sample was primarily male, Caucasian, and a mean age of 14.8 years at baseline. The baseline Tanner stage for 70% of subjects was consistent with chronological age. For the majority of subjects who reached 12 - 20 months (N = 25) or 24 months (N = 21) endpoints, the Tanner stage at respective endpoints was consistent with age. We found that progression in Tanner stage was not associated with OROS MPH duration or dose (p > 0.10). Long-term treatment with extended release methylphenidate did not appear to adversely impact pubertal development in this sample of adolescents with ADHD.
文摘Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40°C/75% RH and 18 Months at 25°C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.
基金funded by Verde Technologies(Minnetonka,MN,USA)as an SBIR PhaseⅡcontract from the National Institute on Drug Abuse(NIDA).Title:In-Home Deactivation System for Psychoactive Drugs(SBIR Phase 2),Contract no.HHSN271201400068C NIDA Reference no.N44DA-14-4420
文摘Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration(FDA) recommends the proper disposal of unused prescribed medications to maintain safety and prevent environmental hazards. However, many of the current disposal techniques do not properly address safety. A drug disposal pouch containing granular activated carbon offers a unique disposal method to deactivate residual or expired medication in a convenient, effective, and safe manner. A robust and validated method for methylphenidate hydrochloride and loxapine succinate was developed using high-performance liquid chromatography(HPLC) and the deactivation efficiency of the disposal system was tested. Methylphenidate hydrochloride was analyzed on a C18 analytical column(250 mm ?4.60 mm, 100?) using acetonitrile-water(0.05%(v/v) trifluoroacetic acid) as the mobile phase at a flow rate of1.0 mL/min with a run time of 15 min and retention time of 7.8 min. Loxapine succinate was separated on a C8100?(250 mm ? 4.6 mm, 5 mm) column maintained at 25 °C using a flow rate of 1.0 mL/min. The run time was 10 min and the retention time of the drug was around 4.6 min. Mobile phase was composed of acetonitrile and water(0.3% triethylamine) at pH 3.0 as 40:60(v/v). Reference standard solutions(100 mg/mL) for both drugs were prepared by dissolving in mobile phases. These methods provide good linearity(R2? 0.999) over the range of 5–100 mg/mL for methylphenidate hydrochloride and 0.1–100 mg/mL for loxapine succinate. The assay methods were successfully applied to study the deactivation of these drugs.
文摘Objectives: This paper deals with the methylphenidate (MPH) misuse by adults in Germany. Results of a survey among primary care physicians/internists have been supplemented by a comparison with the literature. Methods: In the period from October 5-20, 2015, a survey was sent to 414 primary care physicians/internists in four German cities (n = 10 were undeliverable). The response rate was 58% (n = 235). 34 original works on MPH abuse worldwide were found in the literature and are used in the analysis of the present data situation. The literature published before November 9, 2015 is considered in this paper. Results: 14% of the doctors who took part in the survey said that they had been asked for MPH prescriptions without any medical indication. The most frequent reason given for the request (42%) was adult attention deficit/hyperactivity disorder (ADHD) not verified by documents. According to the comparison with the literature, university students had a lifetime prevalence of MPH misuse ranging from 0.8% to 16.6% and school children had a misuse rate of 4.0%. In the civilian US population, the misuse rate was 4.2%. Among patients in possession of a current MPH prescription due to a diagnosis, the lifetime prevalence was 29% and among adolescents with suspected alcohol and/or drug problems 20%. Conclusions: MPH misuse is a major problem which has not been studied sufficiently. MPH misuse not only plays a role in the field of psychiatry, but also in other disciplines. Misuse particularly following a therapeutic prescription should be taken into account.
文摘Operant conditioning of the electroencephalographic rhythm (EEG biofeedback) is argued to be an effective method for treating children with ADHD. This study was designed to evaluate whether this method, compared to methylphenidate, achieves an equally effective outcome. Participants were 39 children aged between 7-12 years. Thirteen children with attention-deficit/hyperactivity disorder (ADHD) were trained to enhance the amplitude of the beta1 activity (15-18 Hz) and decrease the amplitude of the theta activity (4-8 Hz), and 13 of which were treated with methylphenidate alone. Thirteen healthy children did not receive intervention. Several behavioral, neuropsychological and experimental tests were administered before and after intervention. While behavioral measures were improved by both types of method, methylphenidate was significantly more effective than EEG biofeedback. Response inhibition was improved only by EEG biofeedback. Both EEG biofeedback and methylphenidate were associated with improvements on the variability and accuracy measures of computerized tests. Intellectual ability increased also by both methods. Although averaged effect size for methylphenidate seems to be greater than for EEG biofeedback, the difference was not significant. In conjunction with other studies, these findings demonstrate that EEG biofeedback can significantly improve several be-havioral and cognitive functions in children with ADHD, and it might be an alternative treatment for non-responders or incomplete responders to medication as well as for those their parents favor a non-pharmacological treatment.
