OBJECTIVEMethylphenidate is recommended as a first-line modality for treating attention deficit hyperactivity disorder (ADHD). In the past, immediate release methylphenidate (IR-MPH) was used for ADHD. Now oral osmotic-methylphenidate (OROS-MPH) is used for ADHD in China. This study was designed to investigate the efficacy and safety of OROS-MPH for treatment of ADHD in children.

METHODSNinety-nine children with ADHD were randomly administered with OROS-MPH (18 mg/time, once daily) and IR-MPH (5 mg/ time, twice or three times per day). After 6 weeks of treatment, the therapeutic effects were evaluated by the SNAP-IV and the IVA-CPT.

RESULTSFifty patients completed the 6-week treatment. The effective rate (83.3% vs 75%) and the complete remission rate (44% vs 25%) in the OROS-MPH treatment group were higher than that in the IR-MPH treatment group. There were statistically significant differences in the SNAP-IV and IVA-CPT scores before and after treatment in the two groups (P<0.01). The two groups had a similar incidence of side effects during treatment.

CONCLUSIONSOROS-MPH for the treatment of ADHD is effective and safe in children, and its once-daily administration is more convenient.

Administration, Oral ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Child ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects

The purpose of this study was to investigate the effects of methylphenidate, a psychostimulant, on quantitative electroencephalography (QEEG) during the continuous performance test (CPT) in boys with attention-deficit hyperactivity disorder (ADHD). The QEEG was obtained from 20 boys with ADHD. The amplitudes of 4 bands (alpha, beta, delta, and theta) in the QEEG, as well as the theta/beta ratio, before and after the administration of methylphenidate were compared during both the resting and CPT states. Methylphenidate induced a significant increase of alpha activities in both the right and left frontal and occipital areas, an increase of beta activities in almost all areas except for the temporal region, a decrease of theta activities in both the occipital and right temporo-parietal areas, a mild decrease of delta activities in the occipito-parietal areas, and an increase of the theta/beta ratio in the right frontal and parieto-occipital, and left temporal areas during the CPT state. No significant QEEG changes were induced by the administration of methylphenidate in the resting state. These data suggest that methylphenidate has greater electrophysiological influences on the cerebral topographical activities during the performance of attentional tasks, as compared to the resting state, in boys with ADHD.
Attention Deficit Disorder with Hyperactivity/*diagnosis/*drug therapy ; Central Nervous System Stimulants/*administration & dosage ; Child ; Electroencephalography/*drug effects ; Humans ; Male ; Methylphenidate/*administration & dosage ; Neuropsychological Tests

OBJECTIVES: ADHD has been known as psychiatric disorder in childhood associated with dopamine dysregulation. The symptoms of ADHD can be treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). In present study, we investigated DAT density using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([123I]IPT SPECT) in children with ADHD before and after treatment with methylphenidate. METHODS: Seven drug-naive children with ADHD and eight normal children were included in the study and performed SPECT 2 hours after an intravenous administration of [123I]IPT. All children with ADHD reperformed [123I]IPT SPECT after treatment with methylphenidate (0.7 mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/ nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/ nonspecific DAT binding ratio of basal ganglia. RESULTS: Children with ADHD had a significantly greater increase of specific/nonspecific DAT binding ratio of right basal ganglia than normal children (Right:z=2.085, p=0.037;Left:z=1.506, p=0.132). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right:t=3.239, p=0.018;Left:t=3.133, p=0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. CONCLUSIONS: The data of this study using methylphenidate in children with ADHD support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.
Administration, Intravenous ; Attention Deficit Disorder with Hyperactivity* ; Basal Ganglia* ; Child* ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Humans ; Methylphenidate* ; Neurotransmitter Agents ; Tomography, Emission-Computed, Single-Photon*

PURPOSE: Attention deficit hyperactivity disorder (ADHD) has been known as psychiatric disorder in childhood associated with dopamine dysregulation. In present study, we investigated changes in dopamine transporter (DAT) density of the basal ganglias using I-123 N- (3-iodopropen-2-yl) -2-carbomethoxy-3beta- (4-chlorophenyl) tropane [I-123 IPT] SPECT in children with ADHD before and after methylphenidate treatment. MATERIALS AND METHOD: Nine drug-naive children with ADHD and seven normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of I-123 IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of specific/nonspecific DAT binding ratios in the basal ganglia. All children with ADHD reperformed [123I]IPT SPECT after treatment with methylphenidate (0.7mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/nonspecific DAT binding ratio of basal ganglia. RESULTS: Children with ADHD had a significantly greater specific/nonspecific DAT binding ratio of the basal ganglia comparing to normal children (Right: z = 2.057, p = 0.041; Left: z = 2.096, p = 0.032). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right: t = 3.239, p = 0.018; Left: t = 3.133, p = 0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. CONCLUSIONS: These findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.
Administration, Intravenous ; Attention Deficit Disorder with Hyperactivity* ; Basal Ganglia* ; Brain ; Child* ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Humans ; Methylphenidate ; Neurotransmitter Agents ; Tomography, Emission-Computed, Single-Photon

BACKGROUNDAttention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.

METHODSThis 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.

RESULTSA total of 1447 children with ADHD (mean age (9.52 ± 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 ± 2.71) versus the score at baseline (10.45 ± 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study.

CONCLUSIONThis open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Child ; Delayed-Action Preparations ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Prospective Studies ; Treatment Outcome

BACKGROUNDAttention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.

METHODSThis 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.

RESULTSA total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study.

CONCLUSIONSThe OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1.

Administration, Oral ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; physiopathology ; Child ; Cognition ; drug effects ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Neuropsychological Tests ; Prospective Studies ; Treatment Outcome

OBJECTIVETo assess and compare the effectiveness and safety of methylphenidate immediate-release tablets (IR-MPH), methylphenidate controlled release tablets (OROS-MPH) and atomoxetine (AHC) for attention deficit hyperactivity disorder (ADHD) in Chinese children.

METHODSRandomized or clinical controlled trials on the effectiveness and safety of IR-MPH, OROS-MPH and AHC for ADHD were searched in electronic databases of CNKI, VIP, CBMDISC online, PubMed, Embase and MEDLINE. Two reviewers independently extracted the data and assessed the quality of the included literatures.

RESULTSEight trials were finally included. IR-MPH, OROS-MPH and AHC were effective for ADHD. OROS-MPH was superior to IR-MPH in the improvement of peer relationship, CGI-I score, mother satisfaction and psychosomatic problems. There were no significant differences in the effectiveness between the AHC and IR-MPH groups. The adverse events related to the therapy with IR-MPH, OROS-MPH or AHC were mild and the incidence rates of adverse events were not significantly different among the three groups.

CONCLUSIONSThe effectiveness of OROS-MPH for the treatment of ADHD is probably superior to IR-MPH, and the effectiveness between AHC and IR-MPH is similar. The three drugs demonstrate the safety and well tolerance.

Atomoxetine Hydrochloride ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Delayed-Action Preparations ; Humans ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Propylamines ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Tablets

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.
Administration, Oral ; Adolescent ; Atomoxetine Hydrochloride/therapeutic use ; Attention Deficit Disorder with Hyperactivity/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Child ; Databases, Factual ; Drug Compounding ; Female ; Humans ; Insurance Claim Review ; Logistic Models ; Male ; Medication Adherence/*statistics & numerical data ; Methylphenidate/therapeutic use ; Odds Ratio ; Republic of Korea ; Retrospective Studies

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.
Administration, Oral ; Adolescent ; Atomoxetine Hydrochloride/therapeutic use ; Attention Deficit Disorder with Hyperactivity/*drug therapy ; Central Nervous System Stimulants/*therapeutic use ; Child ; Databases, Factual ; Drug Compounding ; Female ; Humans ; Insurance Claim Review ; Logistic Models ; Male ; Medication Adherence/*statistics & numerical data ; Methylphenidate/therapeutic use ; Odds Ratio ; Republic of Korea ; Retrospective Studies