Rapid improvement in academic grades following methylphenidate treatment in attention-deficit hyperactivity disorder
Dr Pinchen Yang, Department of Psychiatry, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung, Taiwan 807. Email: firstname.lastname@example.org
Abstract In the present study a 16 week comparison study was conducted of behavioral, cognitive and educational measures in school-age Taiwanese children with attention-deficit hyperactivity disorder (ADHD) receiving open-label methylphenidate (MPH). Subjects include 14 male and five female ADHD children. They received MPH twice per day continuously for 16 weeks. Measures of behavior, cognitive function (Wisconsin Card Sorting Test, Tower of London and Continuous Performance Test), Chinese and arithmetic learning achievement were compared with those of their baseline condition. After MPH, 68–78% of children showed improving behavior in classroom and at home. Among the neuropsychological tests, only the percentage of preservative error was improved (P = 0.022). Approximately 61–66% of children had improvement in academic learning (P = 0.013 for Chinese, 0.004 for arithmetic). The MPH treatment demonstrated improvement in domains of classroom/home behaviors and academic performance, but showed minimal change on neuropsychological functioning in Taiwanese ADHD children. The finding of academic gain was unexpected, which might be due to the greater interest in achievement and better compliance to cultural expectations by Taiwanese versus Western students, which translated into more rapid improvement in academic performance.
Attention-deficit hyperactivity disorder (ADHD) consists of a heterogeneous group of children who have a developmentally inappropriate level of inattention, impulsivity and hyperactivity, which causes impairment in life.1 Psychostimulant medication, such as methylphenidate (MPH), is the most commonly prescribed psychotropic treatment for children with ADHD.2 This medication has a demonstrated efficacy in a wide spectrum of abnormal behaviors including impulsive behavior, noisiness, non-compliance, disruptiveness, mother–child interactions, peer relationship and classroom behavior. There were multiple randomized clinical trials demonstrating good short-term efficacy in reducing the symptoms of ADHD by MPH.3–5 Nevertheless, even though stimulants may produce significant improvements in daily class performance, long-term academic achievement and social skill have failed to show consistent benefits in previous Western studies.6,7 Recently there have been growing numbers of studies reporting impaired neuropsychological performance involving executive function (EF), abstraction–flexibility, memory and vigilance in ADHD children.8 However, the question of whether MPH can improve EF is still an unsettled issue.
The present study aimed to monitor Taiwanese ADHD children's performance during a continuous 16 week open-label MPH treatment on three domains: behavioral manifestation, academic performance and cognitive function. The purpose was to explore the pharmacological treatment effectiveness in Asian ADHD children, and to evaluate possible outcome differences from previous Western reports.
Subjects were 6–12-year-old children recruited from the outpatient service of Department of Psychiatry, Kaohsiung Medical University Hospital. Children were required to meet the following criteria: (i) diagnosed as attention-deficit hyperactivity disorder, combined subtype by a child psychiatrist (PY) using Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV);1 (ii) maternal report of developmental history consistent with ADHD; and (iii) absence of gross neurological, sensory, or motor impairment as determined by pediatric examinations. Children who had the following comorbid psychiatric diagnosis were excluded: conduct disorder, oppositional defiant disorder, anxiety disorder, dyslexia, depressive disorder, bipolar disorder, autistic dis-order, psychosis and Tourette's disorder. All children attended public elementary schools. Only children with normal intelligence were recruited. The IQ was ascertained through either individual test (Wechsler Intelligence Scale for Children-III9) administered by clinical psychologist or through group test (Standard Progressive Matrices10) arranged by teachers. For those candidate subjects, parents gave written informed consent for participating in a 16 week medication treatment program and their treatment adherence was monitored by biweekly clinic visit over the whole period. A total of 25 children was enrolled and they all received MPH. For a child whose bodyweight was <30 kg, MPH was started at 5 mg twice per day (in the morning before class and at 1 pm after lunch). For the child whose bodyweight was ≥30 kg or more, MPH was started at 10 mg twice per day. Dosage was adjusted with maximal allowance of 1 mg/kg per day in the first 3 weeks of the study, and this adjusted dose was fixed until the completion of 16 weeks of treatment.
At the baseline, subjects received the following evaluations.
(1) Werry–Weiss–Peters Activity Scale for Parents-Chinese Version (WWPAS) and Conners, Werry–Quay Activity Scale for Teachers-Chinese Version (CTRS). These two scales consist of 27 items for parents and 34 items for teacher, respectively. They were adapted from Conners’ Activity Rating Scale11; were validated in Taiwan since 1978 and have been applied extensively in clinical use.12,13
(2) Cognitive tests: Continuous Performance Task (CPT), Tower of London (TOL), and Wisconsin Card Sorting Test (WCST). Details of these tests are described in the following section.
(3) Chinese and mathematics learning assessment. Taiwanese elementary schools routinely hold monthly examinations on Chinese, arithmetic, and science as an evaluation of children's learning progress for the past 1 month. Children who perform at the top 20% of the class would be graded as A, while students who perform at the bottom 20% of the class would be graded as E.
The activity rating scales were given at the end of the first, second, third and fourth month follow up. The cognitive tests were done at the baseline and at the end of the study. Academic achievement reports were obtained from school at the baseline and at the end of the study.
Continuous Performance Task
We used a CPT14 machine from Sunrise system v2.26 (Pembroke MA, USA), which is based on the work of Dr Allan Mirsky's laboratory.15 This is a vigilance test during which numbers are presented on a display screen and the stimulus stays on for 950 msec with a 50 msec delay between presentations. There were 31 target pairs (1 then 9) presented during a total of 310 stimuli. Scores were the number of omissions and number of commissions.
Wisconsin Card Sorting Test
The test consists of 128 cards with sets of geometric designs that vary according to color, form and number.16 The subject was given four cards and then asked to sort the remaining deck of cards using feedback provided by the examiner. Scoring includes the total categories achieved, percentage of preservative errors.
Tower of London Task
The task consisted of a three-peg board with three moveable wooden discs; this is one of the possible ways to assess working memory. The subjects’ task was to move the discs from a standard start position to a target position in a minimum number of moves. Administration of the test followed the standardized procedure outlined by Krikorian et al.17 and task performance recorded as raw score was used for analysis.
Of the 25 children recruited for the present study, 19 subjects completed the 16 week open-label treatment and their results were analyzed by paired t-test. Two children dropped out from the treatment program due to intolerable medication side-effect. Four children's results were removed from final analysis due to medication non-compliance. Of the 19 children who completed treatment program, there were 14 boys and five girls. Full Intelligence quotients were available in 10 children with an average of 100 (range: 86–129). The other nine children's intelligence was estimated to be normal by group tests (Standard Progressive Matrices) scoring between P60 and P80.The average age was 8 years 8 months (range: 6 years 4 months−11 years 10 months, SD = 19.9 months). The average bodyweight was 30 kg (range: 19–41 kg, SD = 6.7 kg). The average MPH dosage was 18.95 mg/day (range: 10–35 mg, SD = 7.56), which was equivalent to 0.61 mg/kg of bodyweight (range: 0.38–0.87 mg/kg of bodyweight, SD = 0.15).
After 16 weeks of MPH treatment, the percentage of children whose raw scores on Teacher Rating Scales (CTRS) showed a 20% decrease was 68.4% (13/19), and the percentage of children whose raw scores on Parents’ Rating Scales (WWPAS) showed a 20% decrease was 77.8% (14/18). Regarding the neuropsychological assessment, pre–post-treatment comparison showed significant difference only in the item of ‘percentage of preservative error’ in WCST (P = 0.022). The performance in CPT and TOL showed no change statistically.
One of the most interesting findings was that the children showed improvement in both Chinese and arithmetic learning as reflected by teacher grading. If we define grades A, B, C, D and E as 1, 2, 3, 4, 5, respectively, 66.6% of children (12/18) showed improvement in Chinese, and 61.1% of children (11/18) showed improvement in arithmetic. Non-parametric Wilcoxon's test was conducted to test the improvement in Chinese and arithmetic between baseline and end of trial. The positive change achieved statistical significance for both Chinese (Z = −2.50; P = 0.013) and arithmetic (Z = −2.84; P = 0.004) performance. Please refer to Table 1 for details.
Table 1. Measurements of ADHD children on MPH for 16 weeks
|Activity scale for teachers||61.68 (18.17)||39.47 (14.47)|| 6.22||<0.001|
|Activity scale for parents||60.67 (12.54)||41.06 (13.67)|| 8.26||<0.001|
| Category|| 3.47 (1.26)|| 4.52 (2.24)||−2.06|| 0.054|
| Percentage error||18.46 (6.16)||14.44 (7.18)|| 2.51|| 0.022|
| Raw score||26.71 (3.90)||27.94 (3.75)||−1.10|| 0.290|
| Omission|| 6.00 (5.17)||3.68 (4.60)|| 1.52|| 0.146|
| Commission||22.11 (26.96)||14.63 (19.26)|| 1.41|| 0.175|
|Chinese|| || ||−2.50|| 0.013|
|Arithmetic|| || ||−2.84|| 0.004|
The efficacy of stimulants in the ADHD children of 6–12 years has been reviewed thoroughly and benefits accepted.7,18 The largest of the stimulant treatment studies, the National Institute of Mental Health Collaborative Multisite Multimodal Treatment Study Of Children With Attention-Deficit/Hyperactivity Disorder (Multimodal Treatment Study), showed that stimulants (either by themselves or in combination with behavioral treatments) lead to stable improvements in ADHD symptoms as long as the drug continues to be taken.5 Overall, most Western studies show between a 60% and 70% response rate on multiple behavioral domains with a generally low placebo response.2 The present study shows that MPH can help approximately 68–78% of Taiwanese ADHD children to improve behaviors in classroom and at home, which is approximately the same rate as in Western reports. Nevertheless, the present mean MPH dosage (19 mg/kg), as determined by adult report regarding behavioral satisfaction in the initial 3 weeks, is relatively low by Western standards.
Reviews regarding neuropsychological studies of frontal lobe functions found a deficit in the executive function of ADHD children.19 The WCST and TOL applied in the present study were two of the frequently used tasks exploring executive functions. Our results showed only one item in WCST (percentage of preservative error) to be improved after MPH treatment. It appears that the main finding was the general absence of improvement on formal cognitive testing. This perhaps means that the children showed more behavioral improvement than cognitive improvement, or perhaps it is a result of the slightly low MPH dose. It may also imply that the neuropsychological paradigms used to explore executive function were inadequate. Also, because of the small sample size and many interference factors, the lack of difference in most of the cognitive tests might not necessarily be meaningful.
Literature search for treated ADHD children showing academic improvement can be found in Western reports.20,21 However, studies of this kind were usually done in the context of an intensive summer treatment program. For example, one study reported stimulant therapy to improve academic performance of 45 ADHD adolescents during a 6 week, placebo-controlled summer treatment program. Participants received a cross-over trial of three doses of MPH and group data showed that the greatest benefit came with the lowest dose.22 Nevertheless, a pessimistic conclusion was drawn from meta-analysis of Western researches, which stated that the effect of stimulants on behavior might be several fold greater than the effects on academic achievement.4 With this impression in mind, our finding of 61–66% of children gaining improvement in academic achievement was something unexpected and deserved consideration. One possibility was that the improvement on the school's academic achievement test was a result of improved test-taking ability on stimulants. That is, perhaps the ‘better grades’ reflect better attention during the exam, or better ability to stay focused throughout the test, or less impulsive completion; rather than an actual academic improvement. This possibility was consistent with the results of behavioral improvement rather than cognitive improvement. Another possibility proposed was that the improvement in academic grades was related to the children's better compliance to mainstream adult expectations, which could be broadly referred to as cultural effect.
There are a few noteworthy limitations to the current study. The foremost is that the present study was conducted in a naturalistic manner, without a placebo-controlled or contrast group and without blinding. No psychosocial interventions were arranged by the hospital for the children, and data regarding further academic support given by each individual's family were not collected. The diagnoses were made by clinicians, without the benefit of standardized diagnostic instruments administered by a blind clinician. However, we believe that this phenomenon and results can thus reflect actual clinical practice results in Taiwan. Also, we did not perform any individually administered standardized tests to measure Chinese reading accuracy or Chinese comprehension or mathematical ability to ascertain the non-existence of comorbid dyslexia or mathematics disorder in our ADHD subjects. We think that this is a weakness that may undermine the interpretation of our results.
Previous prospective and retrospective studies indicate that children with ADHD are at a higher risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning.23,24 We believe that cross-cultural comparison on longitudinal follow up of ADHD children is needed for further understanding of the possible cultural mediating effect of this disorder, treated or not, across the lifespan. If verified in other cross-culture comparison studies, the hypothesis of culture shaping the unfolding of a developmental disorder, such as ADHD, should have important implications for how Western students could be helped by more intensive social and academic support.