Gabapentin and methylphenidate treatment of a preadolescent with attention deficit hyperactivity disorder and bipolar disorder

Gabapentin is an anticonvulsant drug released in the United States in 1993 for use as adjunctive therapy in refractory partial epilepsy. The mechanism of action of gabapentin is unknown, but the drug has very favorable pharmacokinetics and a good safety profile, which allows its use in high-risk patients. Several reports have described the successful use of gabapentin for bipolar disorders in adults, but there are no controlled studies in the use of gabapentin in children and adolescents. We describe a 12-year-old boy with a history of attention deficient hyperactivity disorder (ADHD), reading disorder, mixed receptive and expressive language disorder, encopresis, and bipolar disorder II who was treated with gabapentin 200 mg/day added to methylphenidate 30 mg/day. Within 3 weeks the improvement and stabilization of mood symptoms was remarkable, as noted by mother, teacher, and clinician, and remained so for 6 months of follow-up. Comorbid bipolar disorder and ADHD is a hotly debated topic in the child and adolescent psychiatric literature, with rates of comorbid ADHD and bipolar disorder ranging from 22% to 90%. Controlled studies are needed to evaluate the possible antimanic mood stabilizing and/or antidepressant properties or gabapentin in youths.     

Combined methylphenidate and atomoxetine pharmacotherapy in attention deficit hyperactivity disorder

Object?ves. Pharmacological treatment of attention deficit hyperactivity disorder (ADHD) includes stimulant and non-stimulant medications. Our purpose in this study is to investigate efficacy, safety and tolerability of combined methylphenidate and atomoxetine pharmacotherapy. Methods. We included 12 patients of the 824 patients with ADHD using methylphenidate and atomoxetine combined therapy between the years 2010 and 2014. Kiddie-SADS, Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale, Child Behavior Checklist, Clinic Global Impression Scale Severity and Impression (CGIS-S-I) scales were used. Results. Patients were between the ages of 7 and 17 years. Before combined pharmacotherapy the CGIS-S score mean was 5.08. Mean CGIS-S score after the combined pharmacotherapy was 3.08 (P = 0.03; –2,980). The most common side effects were irritability (n = 5, 41.6%), appetite reduction (n = 3, 25%), palpitations (n = 2, 16.7%), headache (n = 1, 8.3%). Conclus?ons. Nine of these 12 patients showed significant improvement in their symptoms, combined therapy enhanced the effectiveness of monotherapy.     

Retrospective comparison of Adderall and methylphenidate in the treatment of attention deficit hyperactivity disorder

Methylphenidate is the most frequently prescribed stimulant medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the short duration of action of methylphenidate requires that patients take multiple daily doses for optimal efficacy. Recent studies suggest that Adderall, a psychostimulant indicated for the treatment of ADHD, may provide an efficacious, less frequently dosed alternative to methylphenidate. This retrospective review compares the efficacy, safety, dosing frequency, and medication switch rates of Adderall with methylphenidate in children and adolescents with ADHD treated in a private, outpatient psychiatric clinic. Of the evaluable patients, 54 received Adderall, and 75 received methylphenidate. No statistically significant differences were noted between Adderall and methylphenidate in efficacy or safety parameters. Fewer patients receiving Adderall required twice daily, thrice daily, or in-school dosing than those receiving methylphenidate (p < 0.001). During the initial 6-month treatment period, patients treated with Adderall were less likely to switch medications than those receiving methylphenidate (p = 0.0002). In this analysis, Adderall and methylphenidate provided comparable efficacy and safety in children and adolescents with ADHD. The use of Adderall allowed patients to extend their dosing interval and reduced the need for in-school dosing, a measure that may substantially influence compliance.     

Clinical use of a modified release methylphenidate in the treatment of childhood attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioural disorder in childhood, affecting over 5% of children worldwide. As well as the core symptoms of inattention, hyperactivity and impulsivity, patients often exhibit learning difficulties and impairment in social functioning. The frequency of referral is higher for boys than for girls (about 2:1), and girls are generally older at the time of referral. Pharmacological therapy is considered the first-line treatment for patients with severe ADHD and severe impairment. Stimulant medications are licensed in the UK for the management of ADHD in school-age children and young people, and are effective in controlling ADHD symptoms. While immediate-release preparations of methylphenidate (MPH) have proven effective in the treatment of ADHD, there are a number of problems associated with their use, most notably compliance, stigma and medication diversion. Modified release preparations are now available that overcome the need for multiple daily dosing, and which offer different MPH release profiles, thereby enabling the physician to match the medication to the patient's particular requirements. This review describes the diagnosis, referral and treatment pathways for patients with ADHD in the UK and the practical considerations when initiating pharmacological treatment. The clinical experience of treating ADHD with a modified-release MPH preparation (Equasym XL^®) is illustrated with case studies.     

Cost-effectiveness of dexamphetamine and methylphenidate for the treatment of childhood attention deficit hyperactivity disorder

OBJECTIVE: To analyze from a health sector perspective the cost-effectiveness of dexamphetamine (DEX) and methylphenidate (MPH) interventions to treat childhood attention deficit hyperactivity disorder (ADHD), compared to current practice. METHOD: Children eligible for the interventions are those aged between 4 and 17 years in 2000, who had ADHD and were seeking care for emotional or behavioural problems, but were not receiving stimulant medication. To determine health benefit, a meta-analysis of randomized controlled trials was performed for DEX and MPH, and the effect sizes were translated into utility values. An assessment on second stage filter criteria ("equity", "strength of evidence", "feasibility" and "acceptability to stakeholders") is also undertaken to incorporate additional factors that impact on resource allocation decisions. Simulation modelling techniques are used to present a 95% uncertainty interval (UI) around the incremental cost-effectiveness ratio (ICER), which is calculated in cost (in A$) per DALY averted. RESULTS: The ICER for DEX is A$4100/DALY saved (95% UI: negative to A$14 000) and for MPH is A$15 000/DALY saved (95% UI: A$9100-22 000). DEX is more costly than MPH for the government, but much less costly for the patient. CONCLUSIONS: MPH and DEX are cost-effective interventions for childhood ADHD. DEX is more cost-effective than MPH, although if MPH were listed at a lower price on the Pharmaceutical Benefits Scheme it would become more cost-effective. Increased uptake of stimulants for ADHD would require policy change. However, the medication of children and wider availability of stimulants may concern parents and the community.     

The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder

OBJECTIVE: Recent studies have suggested that attention deficit hyperactivity disorder (ADHD) is associated with abnormalities in basal ganglia and prefrontal cortical functioning. However, these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms. METHOD: The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a randomized, double-blind, placebo-controlled pharmacological challenge with methylphenidate in 15 adolescents with ADHD (ages 14-17), eight adolescents with reading disorder (ages 12-17), and four adolescents with both reading disorder and ADHD (ages 14-18) who were scanned during both a methylphenidate and a placebo session. Fourteen healthy comparison subjects (ages 12-20) who were not given methylphenidate served as the primary comparison group. RESULTS: During the divided attention task, unmedicated subjects with ADHD or reading disorder recruited the left ventral basal ganglia significantly less than the healthy comparison subjects. Methylphenidate led to an increase in activation in this region but had no effect on task performance. Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects, but methylphenidate did not have a direct effect on activation in this region. CONCLUSIONS: These results suggest that ADHD is associated with abnormal processing in attentional networks, with specific dysfunction in striatal circuitry. Methylphenidate may act to normalize activity within this network.     

Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial

OBJECTIVE: Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS: Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.     

Clinical use of 30:70 controlled-release methylphenidate in the treatment of attention deficit hyperactivity disorder

INTRODUCTION. Attention deficit hyperactivity disorder (ADHD) is one of the most frequent reasons for visits in daily clinical practice, with a prevalence rate of 1-7% in Spain. The effectiveness of stimulants for the treatment of ADHD has been widely demonstrated and methylphenidate (MPD) is the most commonly used. There are currently several different immediate-release or extended-release formulations of MPD on the market. AIMS. To review the characteristics of the different formulations of MPD, with special attention paid to the studies on Equasym ?, an extended-release preparation soon to be made available in Spain. The article also includes recommendations for clinical practice and the choice of drugs. DEVELOPMENT. Several studies have assessed the effectiveness of Equasym ? versus placebo or in comparison to other MPD formulations. The extended-release preparations have a therapeutic action that is similar to that of the immediate-release versions, the difference between them being the plasma concentration profiles over time during the day, which are reflected in the pharmacodynamic effects. Equasym ? is more effective in the morning, whereas other formulations, such as Concerta ?, allow greater control of the symptoms in the afternoon. These differences are important when it comes to prescribing the treatment. CONCLUSIONS. One of the main advantages of having different formulations of MPD available is that it allows the professional to choose the drug that best suits the clinical features and needs of each patient. The individual response is the essential criterion in deciding on the most appropriate treatment.     

注意缺陷多动障碍儿童哌醋甲酯治疗前后错误监控功能的动态观察

目的探讨注意缺陷多动障碍儿童的错误相关负电位（error-related negativity,ERN）变化与治疗的关系。方法应用德国Brain Products公司的ERP记录与分析系统,对38例ADHD和30名健康儿童作了ERN检测。结果（1）注意缺陷多动障碍组的正确反应率明显低于健康儿童组,正确反应和错误反应的反应时明显比健康儿童组长。（2）与健康儿童组相比,注意缺陷多动障碍ERN潜伏期在Cz、Oz、C3和C4上明显延迟,波幅（Cz、C3、Oz、Pz）较健康儿童组低。（3）患者组在治疗后6月、18月随访时,ERN潜伏期和波幅差异无显著性（P〉0．05）。结论注意缺陷多动障碍儿童的ERN潜伏期和波幅异常,可能反映了本组儿童内在错误监控机制存在缺陷。随访ERN变化可能是一种属性标志。     

Pharmacologic treatment of attention deficit hyperactivity disorder.

This article describes the role of psychostimulant medication in the treatment of attention deficit hyperactivity disorder. Included are the drugs' putative mechanisms of action, pharmacology, toxicology, indications for their use, short-term and long-term actions, adverse effects, specific dosing regimens, therapeutic monitoring techniques, alternative medications, and drug interactions.     

Atomoxetine in the treatment of attention deficit hyperactivity disorder

Atomoxetine (Strattera, Eli Lilly & Co.) is a highly selective noradrenaline reuptake inhibitor and the first nonstimulant medication to be approved for the treatment of attention deficit hyperactivity disorder. Currently, nine published clinical trials have documented the safety and efficacy of atomoxetine in the treatment of children, adolescents and adults with attention deficit hyperactivity disorder and data presented throughout the past year at national scientific meetings has further addressed its utility. This article reviews the available information on atomoxetine, accompanied by a discussion of its clinical use.     

Gait in attention deficit hyperactivity disorder

Abstract Background Cognitive function and the loading of attention presumably play an important role in gait as well as in fall risk, but previous work has not demonstrated this in any cause-and-effect way. Objectives To gain insight into the relationship between gait and cognitive function, we sought: (1) To compare the gait rhythmicity (stride time variability) of children with attention deficit hyperactivity disorder (ADHD) to controls, (2) To test the hypothesis that dual tasking leads to increased stride-to-stride variability in ADHD, and (3) To test whether pharmacological treatment that relieves ADHD symptoms reduces stride-to-stride variability. Patients and Methods Gait was quantified in children with ADHD and in age-matched healthy controls under single task and dual task conditions on three occasions: off medications (both groups) and, in the ADHD group, after double blinded, randomized administration of methylphenidate (MPH) or placebo. Results At baseline, children with ADHD tended to walk with increased stride-to-stride variability compared to the controls during the single task condition (p = 0.09). During dual task walking, stride time variability was significantly reduced in the children with ADHD (p < 0.004), but not in the controls. In the children with ADHD, the placebo did not significantly affect stride-to-stride variability or the dual tasking response. In contrast, stride time variability was significantly reduced on MPH (p < 0.001) such that dual tasking no longer affected variability. Conclusions The present findings demonstrate alterations in the gait of children with ADHD, support a cause and effect link between cognitive function and gait, and suggest that enhancement of attention abilities may, in certain populations, improve gait rhythmicity.     

Multicomponent attention deficits in attention deficit hyperactivity disorder

The aim of this study was to examine the specific aspects of attention, such as selective attention, sustained attention, and short-term memory in children with attention deficit hyperactivity disorder, combined subtype (ADHD-C). A total of 40 children with a diagnosis of ADHD from the 4th edition of the Diagnostic and Statistical Manual, aged 6-11 years old were compared with 40 controls matched for age and gender on a battery of tests. Short-term memory span and attention was measured by Visual Aural Digit Span Test-Revised. Stroop test and the Turkish version of Cancellation Test were used to assess selective and sustained attention, respectively. In order to check for factor structure in two groups on the test scores, principal component analysis was conducted for both groups separately. Relative to the comparison children, children with ADHD showed significant deficits on tests that are related to different aspects of attention. The results are consistent with the theories explaining the biological basis of ADHD by scattered attention networks in the brain, which have reciprocal dynamic interactions. Further comparative studies are needed to elucidate whether the cognitive processes that are known to be assessed by these tests are specific to ADHD.     

Neurobiology of attention deficit hyperactivity disorder

This article addresses the current understanding of the neurobiological bases of attention deficit hyperactivity disorder (ADHD), focusing on empiric research findings that connect genetic and environmental factors to structural and functional brain abnormalities, ultimately leading to a set of age-dependent behavioral manifestations. Section one presents evidence for genetic risk factors for ADHD and discusses the role of potential environmental factors in the etiology of the disorder. Section two focuses on brain imaging studies and how they have helped generate different hypotheses regarding the pathophysiology of ADHD. Finally, the article addresses the longitudinal course of symptoms in ADHD from infancy to adulthood in an attempt to place biological findings for this complex brain disorder in the context of maturation and development.     

Genetics of attention deficit hyperactivity disorder

Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. In contrast to a handful of genome-wide scans conducted thus far, many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. Yet, even these associations are small and consistent with the idea that the genetic vulnerability to ADHD is mediated by many genes of small effects. These small effects emphasize the need for future candidate gene studies to implement strategies that will provide enough statistical power to detect such small effects.