How Missing a Treatment of Mixed Amphetamine Salts Extended Release Affects Performance in Teen Drivers with ADHD

Mixed Amphetamine Salts Extended Release (MAS-XR or Adderall XR®) is a stimulant medication used to control symptoms of ADHD. People occasionally fail to take their medications. The goal of this pilot study was to assess the impact of a single missed medication on driving performance in 14 teen drivers with ADHD mixed type as a function of driving skill. A double-blind placebo control crossover design was used and participants were tested in a driving simulator. On the evening of the first day, baseline measures of driving performance were taken to assess driving skills (on medication). Then on two consecutive days drivers were tested three times a day, one day on medication and the other day off. Results indicated increased collisions and hazard response time off medication, with performance worst on 36 hours post-medication. Participants with the least developed driving skills benefited most from medication. This highlights the importance of consistent medication use in inexperienced teen drivers with ADHD

The Use of Amphetamines for Improving Cognitive Impairment in Patients with Multiple Sclerosis

Background: Multiple sclerosis (MS) is an autoimmune disorder that results in debilitating cognitive impairment in 40-65% of patients. There are no current treatments for this symptom of MS. This is a systematic review of literature on the impact amphetamines have on cognitive function of MS patients. Methods: An exhaustive search of available medical literature was conducted using MEDLINE-Ovid, MEDLINE-PubMed, Web of Science, and CINAHL. Keywords used included: amphetamines and multiple sclerosis. Relevant articles were assessed for quality using GRADE. Results: Three studies have statistically significant improvements in some aspects of cognitive function in patients on amphetamines when compared to placebo. However, a high rate of adverse events were noted with L-isomer or D-isomer amphetamines alone. Conclusion: Amphetamines positively impact cognitive function in MS patients. Mixed amphetamine salts extended release (MAS-XR) seemingly have the lowest rate of adverse effects with the greatest benefit per the Morrow & Rosehart study. Further research is needed to integrate this into a clinical setting. Keywords: Amphetamines, multiple sclerosi

Stimulant drug effects on attention deficit/hyperactivity disorder: a review of the effects of age and sex of patients

Objective: As dopamine functioning varies by sex and age it might be expected that the effects of methylphenidate or amfetamine, the psychostimulants used for the treatment of Attention Deficit /Hyperactivity Disorder (ADHD), will also be moderated by these factors. Here we review the published literature on whether stimulant effects in ADHD symptoms vary by age and sex. Method: We searched for studies published from 1989 until October 2009. Databases searched included U. S. National Library of Medicine (PubMed), Medline, EMBASE, PsycINFO and ISI Web of Knowledge. Firstly, we reviewed the effects of stimulant drugs on male and female patients and also patients of pre-school, middle childhood, adolescence and adulthood. Secondly, we reviewed studies that directly tested the moderating effect of age and sex on stimulant treatment outcome. Results: Randomised controlled trials confirm that stimulant medication is efficacious for, and well tolerated by, males and females and patients across the age range; although preschoolers appear to have a less beneficial response and more side effects. Few studies that specifically examined the moderating effect of age and/or sex were identified. For sex, no effects on overall response were found, although one study reported that sex moderated methylphenidate pharmacodynamics. The few effects found for age were small and inconsistent. Conclusions: The available evidence suggests that stimulant medication, when appropriately administered, has efficacy as an ADHD treatment for both sexes and across all ages. There are currently too few published papers examining the effects of sex and age to draw strong conclusions about moderation. Further studies of the pharmacodynamics of stimulants on symptoms measured using objective tests in the laboratory or classroom setting need to be undertaken

The Use of Drug Therapy for Attention Deficit Hyperactivity Disorder (ADHD) in the Management of Oppositional Defiant Disorder (ODD): A Literature Review

Children with oppositional defiant disorder (ODD) and a concurrent Axis I diagnosis are often prescribed drug therapy for attention deficit hyperactivity disorder (ADHD) to manage disruptive behavior. However, ODD symptoms tend to be poorly controlled, raising questions about the effectiveness of drug therapy in children with the condition. Safety and long term consequences of pharmacological agents for ODD are important factors clinicians must consider before initiating treatment. The purpose of this literature review is to examine the pharmacodynamics and efficacy of drug therapy used for ODD in school-age children and adolescents. Additionally, awareness of poor behavior patterns and recognition of symptoms associated with ODD in children among health care providers was explored. A literature review exploring ODD and drug therapy for ODD and related behavioral disorders was conducted from various online databases. Results from 15 reviewed studies suggest that pharmacologic therapy is typically prescribed for ODD symptoms when a comorbid condition such as ADHD, a mood disorder, or an anxiety disorder is present. Drug therapy for ADHD has demonstrated effective behavioral outcomes in reducing ODD symptom severity in children and tolerable side effects when used for short-term therapy. Studies have demonstrated success and better control of ODD symptoms with a focused drug therapy regimen. Overall, the benefits of drug therapy can potentially outweigh the risks of adverse effects, and improve the quality of life in children with ODD. In conclusion, uncovering the reasons for poorly controlled ODD in children can be of clinical significance to health care providers and can support decision making when considering drug therapy for children with this condition

Treatment of adult ADHD: Is current knowledge useful to clinicians?

Psychostimulant drugs have for decades been considered the cornerstone of ADHD treatment. Non-stimulant drugs have also been reported successful. However, many controlled studies exclude patients with comorbidities typical for patients seen in clinical setting. Many patients are also considered non-responders to medication. Current knowledge might not be directly useful to clinicians. The present article reviews the literature on pharmacological and psychotherapeutic treatment in adult ADHD emphasizing comorbidity and other clinically important factors, as well as ADHD specific outcomes. Thirty-three relevant studies of pharmacotherapy and three studies of psychotherapy were included. Most subjects had little current comorbidity, but some studies included subjects with substance use disorder. Significant effect of treatment on ADHD symptoms was found in most studies using pharmacotherapy and all studies of psychotherapy. Both positive and negative effects on comorbid anxiety and depression measures were reported. Pharmacotherapy did not seem to have effect on substance use disorder. Few pharmacotherapy studies conducted any long-term follow-up; two studies that did, found that most subjects had discontinued medication. A clear-cut dose-respons relationship was not substanciated. In conclusion, clinicians have good support for both pharmacological and psychotherapeutic treatment of ADHD in adults, but should take additional measures to deal with comorbidities as well as treatment adherence

Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

David R Coghill,1 Tobias Banaschewski,2 Michel Lecendreux,3 César Soutullo,4 Alessandro Zuddas,5 Ben Adeyi,6 Shaw Sorooshian7 1Division of Neuroscience, University of Dundee, Dundee, UK; 2Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 3Paediatric Sleep Centre and National Reference Centre for Orphan Diseases: Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Robert-Debré University Hospital, Paris, France; 4Child and Adolescent Psychiatry Unit, Department of Psychiatry and Medical Psychology, University of Navarra Clinic, Pamplona, Spain; 5Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; 6Shire, Wayne, PA, USA; 7Shire, Eysins, Switzerland Background: Following the approval of lisdexamfetamine dimesylate (LDX) in several European countries for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with an inadequate response to methylphenidate (MPH) treatment, the aim of the present analysis was to establish the response to LDX in subgroups of patients with different ADHD medication histories. Methods: This was a post hoc subgroup analysis of data from a 7-week, European, double-blind, dose-optimized, Phase III study. Patients aged 6–17 years were randomized 1:1:1 to LDX, placebo, or osmotic-release oral system methylphenidate (OROS-MPH). OROS-MPH was included as a reference arm rather than as a direct comparator. Efficacy was assessed in patients categorized according to their ADHD medication history using the ADHD Rating Scale IV and Clinical Global Impressions-Improvement (CGI-I) scores. Results: The difference between active drug and placebo in least-squares mean change from baseline to endpoint in ADHD Rating Scale IV total score (95% confidence interval) was similar between the overall study population (n=317; LDX, -18.6 [-21.5, -15.7]; OROS- MPH, -13.0 [-15.9, -10.2]) and treatment-naïve individuals (n=147; LDX, -15.1 [-19.4, -10.9]; OROS-MPH, -12.7 [-16.8, -8.5]) or patients previously treated with any ADHD medication (n=170; LDX, -21.5 [-25.5, -17.6]; OROS-MPH, -14.2 [-18.1, -10.3]). In addition, similar proportions of patients receiving active treatment were categorized as improved based on CGI-I score (CGI-I of 1 or 2) in the overall study population and among treatment-naïve individuals or patients previously treated with any ADHD medication. Conclusion: In these post hoc analyses, the response to LDX treatment, and to the reference treatment OROS-MPH, was similar to that observed for the overall study population in subgroups of patients categorized according to whether or not they had previously received ADHD medication. Keywords: attention-deficit/hyperactivity disorder, lisdexamfetamine dimesylate, methylphenidate, central nervous system stimulant

Time courses of improvement and symptom remission in children treated with atomoxetine for attention-deficit/hyperactivity disorder: analysis of Canadian open-label studies

<p>Abstract</p> <p>Background</p> <p>The relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD) provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scales, during up to 1 year of atomoxetine treatment in children with ADHD.</p> <p>Methods</p> <p>Using pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1) improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2) remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2.</p> <p>Results</p> <p>The median time to improvement was 3.7 weeks (~1 month), but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months) using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale) and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale). The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03) was not statistically significant (<it>p </it>= .33).</p> <p>Conclusions</p> <p>Reductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study participants showed improvement at 1 month of atomoxetine treatment, remission criteria were not met until about 3 months. Understanding the time course of children's responses to atomoxetine treatment may inform clinical decision making and also influence the durations of trials comparing the effects of this medication with other ADHD treatments.</p> <p>Trial Registrations</p> <p>clinicaltrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00191633">NCT00191633</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00216918">NCT00216918</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00191880">NCT00191880</a>.</p