Adolescent ; Attention ; drug effects ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; physiopathology ; Child ; Electroencephalography ; drug effects ; Female ; Follow-Up Studies ; Humans ; Male ; Psychomotor Performance ; Treatment Outcome

OBJECTIVE: To study the relation between human blood estazolam concentration and neurobehavioral function. METHODS: The neurobehavioral ability of 10 volunteers were measured with computer-administered neurobehavioral evaluation system-chinese3 (NES-C3) and SMART EquiTest system. RESULTS: The neurobehavioral ability and balance function declined 1 h later after dosing estazolam. The neurobehavioral ability index and balance function declined to the lowest level 3 h later after dosing estazolam. The neurobehavioral ability recovered partly 6 h later after dosing estazolam, and neurobehavioral ability recovered completely 10 h later. CONCLUSION Driving ability was impaired when estazolam concentration in blood is 20 ng/mL, and the neurobehavioral ability declined when estazolam concentration is 40 ng/mL in blood. The influence to human in absorption process is greater than the metabolic process with the same estazolam concentration.
Accidents, Traffic/prevention & control* ; Administration, Oral ; Adult ; Anticonvulsants/pharmacokinetics* ; Attention/drug effects* ; Behavior/drug effects* ; Estazolam/pharmacokinetics* ; Female ; Humans ; Male ; Neuropsychological Tests ; Psychomotor Performance/drug effects* ; Reaction Time

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

OBJECTIVETo investigate the effect of baicalin on the behavioral characteristics of rats with attention deficit hyperactivity disorder (ADHD), and to provide a basis for further research on baicalin in the treatment of ADHD.

METHODSA total of 40 SHR rats were randomly divided into model group, methylphenidate hydrochloride (MPH) group, and low-, medium-, and high-dose baicalin groups, with 8 rats in each group. Eight WKY rats were selected as normal control group. The rats in the MPH group (0.07 mg/mL) and the low- (3.33 mg/mL), medium- (6.67 mg/mL), and high-dose (10 mg/mL) baicalin groups were given the corresponding drugs (1.5 mL/100 g) by gavage twice a day, and those in the normal control group and the model group were given an equal volume of normal saline by gavage twice a day. The course of treatment was 4 weeks for all groups. The open field test was performed to observe total moving distance and average moving speed on day 0 of experiment and at 7, 14, 21, and 28 days after gavage and to evaluate the control effects of drugs on hyperactivity and impulsive behavior. The Morris water maze test was used to observe the latency, time spent in the target quadrant, and number of platform crossings and to evaluate the effects of drugs on attention.

RESULTSThe open field test showed that the model group and the drug treatment groups had a significantly longer total moving distance and a significantly higher average moving speed than the normal control group on day 0 (P<0.05). On day 7, the MPH group had significant reductions in total moving distance and average moving speed compared with the model group (P<0.05). On day 14, the MPH group and the high-dose baicalin group had significant reductions in total moving distance and average moving speed compared with the model group (P<0.05). The data on days 21 and 28 showed that compared with the model group, the low-, medium-, and high-dose baicalin groups had gradual reductions in total moving distance and average moving speed (P<0.05). The water maze test showed that compared with the model group, the MPH group and the medium- and high-dose baicalin groups had a significantly longer time spent in the target quadrant (P<0.05), and the MPH group and the high-dose baicalin group had a significantly higher proportion of the moving distance in the target quadrant in total moving distance (P<0.05). The high-dose baicalin group had the highest number of platform crossings among all groups (P<0.05).

CONCLUSIONSBoth baicalin and MPH can regulate the motor ability and learning and memory abilities of SHR rats with ADHD and thus control the core symptoms of ADHD, i.e., hyperactivity, impulsive behavior, and inattention. Baicalin exerts its effect in a dose-dependent manner, and high-dose baicalin has the most significant effect, but compared with MPH, it needs a longer time to play its therapeutic effect.

Animals ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; psychology ; Behavior, Animal ; drug effects ; Dose-Response Relationship, Drug ; Flavonoids ; therapeutic use ; Male ; Maze Learning ; drug effects ; Motor Activity ; drug effects ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

OBJECTIVETo determine whether long-term treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate influences the growth in height and weight of children.

METHODSAnalyses were performed on 146 school age children (126 boys) diagnosed as ADHD and treated with methylphenidate [0.27-0.64 mg/(kg.day)] for methylphenidate group and 29 children with ADHD who did not receive any medication for ADHD (controls). These children were followed-up for 2-4 years. Changes in height and weight after long-term treatment with methylphenidate were recorded and the factors affecting growth of height, weight, and height velocity were analyzed.

RESULTSThe change of difference between patients' height and mean height in methylphenidate group and controls was (-1.86 +/- 0.82) cm (paired t test, t = 27.335, P < 0.001) and (-0.26 +/- 0.51) cm (P < 0.05), respectively; the change of height standard deviation score (SDS) in methylphenidate group and controls was -0.14 +/- 0.23 SD (paired t test, t = 7.326, P < 0.001) and +0.05 +/- 0.10 SD (P < 0.05), respectively. When the height change and height SDS change in methylphenidate group and controls were compared by using independent-samples T-test, the t value was -10.078 and -4.262 respectively, P for both was < 0.001. Both of bivariate correlation analysis and stepwise multiple-regression analysis indicated that the duration of treatment contributed significantly to the variance in change of height (P < 0.001); but age, sex, DSM-IV type, NJ22 degree and dose of methylphenidate did not contribute significantly to the variance of height. The mean height velocity from 1st to 4th year was 4.28 cm/year, 4.90 cm/year, 4.98 cm/year and 4.95 cm/year, respectively. With Friedman test, Chi-square = 253.673, P < 0.001. The change of difference of patients' weight to weight for height after methylphenidate was (-0.14 +/- 1.25) kg (paired t test, t = 1.326, P > 0.05).

CONCLUSIONSmall but significant deceleration of height velocity is the identified long-term side effect of methylphenidate, the magnitude of height deficit is related to duration of treatment. The height velocity was significantly attenuated in the first year. Methylphenidate had no significant influence on weight.

Attention Deficit Disorder with Hyperactivity ; drug therapy ; Body Height ; drug effects ; Body Weight ; drug effects ; Case-Control Studies ; Central Nervous System Stimulants ; adverse effects ; therapeutic use ; Child ; Child Development ; Female ; Humans ; Male ; Methylphenidate ; adverse effects ; therapeutic use ; Regression Analysis

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

PURPOSE: Evidence suggests that some patients with breast cancer experience cognitive difficulties following chemotherapy. This longitudinal study was done to examine the prevalence of cognitive impairment and trajectory of cognitive function over time in women with breast cancer, who received adjuvant chemotherapy. METHODS: Participants were 137 patients with breast cancer. They completed neuropsychological tests and the Functional Assessment of Cancer Therapy-Cognitive Function before adjuvant therapy (pretest), toward the end of adjuvant therapy (posttest), and 6 months after the completion of adjuvant therapy (follow-up test). Of the patients, 91 were treated with adjuvant chemotherapy and 46 patients who did not receive chemotherapy made up the comparison group. A reliable-change index and repeated-measure ANOVA were used for statistical analyses. RESULTS: At the posttest point, over 30% of patients showed complex cognitive impairment and reported greater difficulty in subjective cognitive function. At the follow-up test point, 22.0% of patients exhibited complex cognitive impairment and 30.8% of patients complained of subjective cognitive impairment. Repeated-measure ANOVA showed significant decreases after receiving chemotherapy followed by small improvements 6 months after the completion of chemotherapy in cognitive domains of change for attention and concentration, memory, executive function, and subjective cognitive function. CONCLUSION: These results suggest that chemotherapy in patients with breast cancer may be associated with objective and subjective cognitive impairments. Further studies are needed to explore the potential risk factors and predictor of chemotherapy-related cognitive changes. Also nursing interventions for prevention and intervention of cognitive impairments should be developed and tested.
Adult ; Analysis of Variance ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Attention/drug effects ; Breast Neoplasms/*drug therapy ; Chemotherapy, Adjuvant ; Cognitive Dysfunction/epidemiology/*etiology ; Female ; Humans ; Longitudinal Studies ; Memory/drug effects ; Middle Aged

The regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment were examined in children with attention deficit/hyperactivity disorder (ADHD). Thirty-two male children, diagnosed with ADHD by the DSM-IV diagnostic criteria, other behavioral assessment scales and neuropsychological battery, were studied using 99mTc-HMPAO-single photon emission computed tomography (SPECT). Subjects were studied before and after MPH treatment. First, using an image subtraction method, we obtained a NDR parametric image of each patient and found increased cerebral blood flow in the frontal lobes, caudate nuclei and thalamic areas after treatment. When the changes in SPECT and clinical response were compared, the matching rate, sensitivity and specificity between them were found to be 77.1, 80.0 and 79.2%, respectively. Second, three transaxial brain slices delineating anatomically defined regions of interest (ROI) at 20, 40, and 60mm above the orbitomeatal line (OML) were used, with the average number of counts for each region of interest normalized to the area of the cerebellar maximal uptake. The left and right prefrontal areas, and caudate and thalamic areas showed significant increases in rCBF after MPH treatment. These findings suggested MPH could affect the function of the fronto-striato-thalamic circuit, which is known as the pathophysiologic site of ADHD and could be used to correct the underlying brain dysfunction of ADHD.
Adolescence ; Attention Deficit Disorder with Hyperactivity/radionuclide imaging ; Attention Deficit Disorder with Hyperactivity/physiopathology ; Attention Deficit Disorder with Hyperactivity/drug therapy* ; Central Nervous System Stimulants/pharmacology* ; Cerebrovascular Circulation/drug effects* ; Child ; Female ; Human ; Male ; Methylphenidate/therapeutic use ; Methylphenidate/pharmacology* ; 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

PURPOSE: The aim of this study was to clarify the relationship between the autonomic nervous system and attention deficit hyperactivity disorder (ADHD) rating scales and to evaluate the usefulness of heart rate variability (HRV) as a psychophysiological biomarker for ADHD. MATERIALS AND METHODS: Subjects were recruited from outpatients in the Department of Child and Adolescent Psychiatry at the Korea University Medical Center from August 2007 to December 2010. Subjects received methylphenidate. Time- and frequency-domain analyses of HRV, the Korean ADHD rating scale (K-ARS), and computerized ADHD diagnostic system were evaluated before treatment. After a 12-week period of medication administration, we repeated the HRV measurements and K-ARS rating. RESULTS: Eighty-six subjects were initially enrolled and 37 participants completed the 12-week treatment and HRV measurements subsequent to the treatment. Significant correlations were found between the K-ARS inattention score and some HRV parameters. All of the HRV parameters, except the standard deviations of the normal-to-normal interval, very low frequency, and low frequency to high frequency, showed a significant positive correlation between baseline and endpoint measures in completers. High frequency (HF) and the square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), which are related to parasympathetic vagal tone, showed significant decreases from baseline to endpoint. CONCLUSION: The HRV test was shown to be reproducible. The decrease in HF and RMSSD suggests that parasympathetic dominance in ADHD can be altered by methylphenidate treatment. It also shows the possibility that HRV parameters can be used as psychophysiological markers in the treatment of ADHD.
Adolescent ; Attention/drug effects/*physiology ; Attention Deficit Disorder with Hyperactivity/diagnosis/*drug therapy ; Autonomic Nervous System/physiopathology ; Biomarkers ; Central Nervous System Stimulants/pharmacology/*therapeutic use ; Child ; Female ; Heart Rate/*drug effects/physiology ; Humans ; Male ; Methylphenidate/pharmacology/*therapeutic use ; Prospective Studies ; Republic of Korea ; Treatment Outcome