Bertrand G. Winsberg

Effects of Methylphenidate Dosage in Hyperactive Reading-disabled Children: II. Reading Achievement

ABSTRACT Effects of methylphenidate (MP) on reading achievement in 7- to 13-year-old children with hyperactivity and reading disorder were investigated. Forty-two children were assigned to one of four MP dose groups (placebo, 0.3 mg/kg, 0.5 mg/kg, and 0.7 mg/kg). Behavior ratings and academic achievement scores were obtained at the beginning of the study, after 12 weekly reading sessions, and again after 12 additional weekly reading sessions. Results showed positive effects of MP on reading that were mediated through behavioral control (i.e., achievement was significantly related to behavioral response to MP treatment), especially during the first 3 months of treatment. A specific effect of MP on word recognition involving verbal retrieval, as opposed to phonic skills, was also found. Implications for clinical treatment are discussed, and questions regarding the interaction of drug dose, behavioral response, and academic learning are posed.

Effects of methylphenidate dosage in hyperactive reading-disabled children: I. Behavior and cognitive performance effects.

ABSTRACT Forty-seven children diagnosed as having Attention Deficit Disorder with Hyperactivity and Developmental Reading Disorder were randomly assigned to receive placebo or one of three methylphenidate dosages (0.3, 0.5, 0.7 mg/kg) twice daily for 6 months, and measurements of social behavior, short-term memory, associative learning, and methylphenidate plasma concentration were obtained at scheduled intervals. Teachers and parents rated hyperactive behaviors as significantly reduced in the 0.7 mg/kg dose group as compared with the placebo group. Where drug effects were obtained on the short-term memory and associative learning tasks, these also resulted in significantly improved performance in the 0.7 mg/kg dose group. Teachers perceived an increase in hyperactivity during the last 3 months of treatment, and this was not explained by changes in methylphenidate plasma concentration. Possible explanations for this unexpected finding in terms of situational factors and drug tolerance are discussed.

Methylphenidate oral dose plasma concentrations and behavioral response in children

The relationship between methylphenidate (MP) oral dose and plasma concentration to social and cognitive behaviors was studied in 25 boys diagnosed as having “attention deficit disorder with hyperactivity”. Children were administered successive 1-week treatment conditions under the following schedule of fixed oral doses given twice daily: placebo; 0.25 mg/kg; 0.50 mg/kg; 1.0 mg/kg; placebo. Teacher and parent ratings showed increased improvement in social behavior as a function of MP dose. No drug effects were obtained on cognitive performance. MP plasma concentrations were significantly associated with oral dose and with measures of social behavior. No relationship was found with cognitive behavior. Side effects at the largest dose were severe enough to require discontinuation of treatment for five children, but were relatively mild for the remaining children.

Learning Ability and Methylphenidate (Ritalin(®)) Plasma Concentration in Hyperkinetic Children: A Preliminary Investigation

Abstract The present study was undertaken to determine whether a relationship exists between methylphenidate (Ritalin(®)) concentration in blood and learning performance in hyperkinetic children. Blood samples were obtained and paired-associate learning performance was evaluated in 5 boys during a predrug baseline and at 1, 2, 3, 5, and 7 hours following their clinically effective dose. A regression analysis yielded a significant negative slope relating plasma concentration and learning errors, suggesting that methylphenidate blood level may significantly influence the academic performance of children being treated with this psychostimulant.

Effects of methylphenidate on learning a ‘beginning reading vocabulary’ by normal adults

The effects of methylphenidate on reading was studied by having nine adults learn a beginning vocabulary of 96 Chinese characters under placebo and 5 mg and 10 mg methylphenidate by two teaching methods which differed in the rate at which new items were introduced for practice. Using lists composed of 12 characters and their English equivalents; all items were presented prior to the start of practice trials (simultaneous method), or each item was introduced only as the subject practiced items previously presented (progressive method). Learning performance was analyzed in terms of total errors and errors made at two criterion stages in list acquisition. Overall performance was significantly facilitated by the low (5 mg) dose of methylphenidate, but only with the simultaneous method. Significant drug effects were also obtained at criterion stages which were associated with high error rates. It was concluded that drug effects are likely to be most pronounced in difficult learning situations and that dosage appears to be an important variable for consideration in further studies.

Ineffectiveness of imipramine in children who fail to respond to methylphenidate

Ten hyperactive children who had failed to respond to methylphenidate were treated with imipramine in a placebo-controlled, crossover design. No significant drug effects were obtained either on parent and teacher ratings of the childs behavior or on the childs performance in a laboratory measure of sustained attention. Findings suggest that imipramine has limited clinical usefulness in the treatment of hyperactive children who fail to respond to methylphenidate.

Neurochemistry of withdrawal emergent symptoms in children

The probenecid procedure was used to study the metabolite accumulations of dopamine (DA) and serotonin (5-HT) in the cerebrospinal fluid (CSF) of 11 children receiving chronic neuroleptic therapy. Specimens were obtained while the children were being given chronically prescribed medication (Condition 1) and again 3–4 weeks later, following the discontinuation of drugs (Condition 2). At that time, five children showed typical dyskinetic withdrawal emergent symptoms (WES) and six were free of symptoms. CSF specimens were also obtained from eight drug-free children, diagnosed as having ‘chronic organic brain disease,’ who served as a contrast population against which the findings were evaluated. CSF accumulations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) did not differentiate the drug-treated children who showed WES from those who did not manifest these symptoms. A significant decrease in 5-HIAA was found in Condition 2, suggesting that chronic treatment with neuroleptics may effect 5-HT metabolism in children. The contrast population was found to have lower CSF concentrations of probenecid and were consequently of little help in clarifying the nature of the 5-HIAA decrement. A number of serious deficiences were noted regarding the use of the probenecid procedure, and it is felt that the use of spinal taps for studying neuroleptic effects on brain metabolism in children is unlikely to provide important information with regard to either CNS drug actions or toxicity.The probenecid procedure was used to study the metabolite accumulations of dopamine (DA) and serotonin (5-HT) in the cerebrospinal fluid (CSF) of 11 children receiving chronic neuroleptic therapy. Specimens were obtained while the children were being given chronically prescribed medication (Condition 1) and again 3–4 weeks later, following the discontinuation of drugs (Condition 2). At that time, five children showed typical dyskinetic withdrawal emergent symptoms (WES) and six were free of symptoms. CSF specimens were also obtained from eight drug-free children, diagnosed as having ‘chronic organic brain disease,’ who served as a contrast population against which the findings were evaluated. CSF accumulations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) did not differentiate the drug-treated children who showed WES from those who did not manifest these symptoms. A significant decrease in 5-HIAA was found in Condition 2, suggesting that chronic treatment with neuroleptics may effect 5-HT metabolism in children. The contrast population was found to have lower CSF concentrations of probenecid and were consequently of little help in clarifying the nature of the 5-HIAA decrement. A number of serious deficiences were noted regarding the use of the probenecid procedure, and it is felt that the use of spinal taps for studying neuroleptic effects on brain metabolism in children is unlikely to provide important information with regard to either CNS drug actions or toxicity.