Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder

The Author(s) 2014. This article is published with open access at Springerlink.com Objectives A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and ato-moxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactiv-ity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously. Methods In this 9-week, double-blind, active-controlled study, patients aged 6–17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients \70 kg: 0.5–1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients C70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (C25, C30 or C50 %) or a Clinical Global Impressions (CGI)–Improvement (CGI–I) score of 1 or 2 throughout weeks 4–9. CGI– Severity (CGI–S) scores were also assessed, as an indicator of remission. Results A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p \ 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also signifi-cantly (p \ 0.05) higher among LDX-treated patient

Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

<p>Abstract</p> <p>Background</p> <p>The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH.</p> <p>Methods</p> <p>Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N = 116), IR-MPH (tid) (N = 102) and OROS-MPH (N = 67).</p> <p>Results</p> <p>Eight-five percent (N = 99) of placebo treated subjects, 77% (N = 79) of the IR-MPH (tid) treated subjects, and 82% (N = 55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9 ± 31.9 mg, 74.8 ± 26.2 mg, and 95.4 ± 26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N = 44) of subjects receiving OROS-MPH and 70% (N = 71) of subjects receiving IR-MPH (tid) were considered responders compared with 31% (N = 36) on placebo.</p> <p>Conclusion</p> <p>Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS-MPH had similar efficacy to that of TID administered IR MPH.</p> <p>Trial Registration</p> <p>The trial of OROS-MPH was registered at clinicaltrials.gov, number NCT00181571.</p

A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): Rationale and design

<p>Abstract</p> <p>Background</p> <p>The ACTION study (<it>Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) </it>is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study.</p> <p>Methods</p> <p>Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo.</p> <p>Results</p> <p>The methodology for the ACTION study has been detailed.</p> <p>Conclusions</p> <p>The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment.</p> <p>Trial registration</p> <p>Australian and New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ANZCTRN12607000535471.aspx">ANZCTRN12607000535471</a>.</p

Atomoxetine for the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a review

Paul Hammerness, Katherine McCarthy, Elizabeth Mancuso, Cassandra Gendron, Daniel GellerClinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital and Harvard Medical School, Cambridge, MA, USAObjective: This review examines and summarizes the pharmacodynamic and pharmacokinetic properties, short- and longer-term efficacy, the moderating effect of comorbid disorders, as well as short- and long-term safety and tolerability of atomoxetine for the treatment of pediatric attention-deficit/hyperactivity disorder (ADHD).Methods: A systematic literature search was performed to review the extant literature on articles pertaining to the pharmacological treatment with atomoxetine in pediatric and/or adolescent ADHD.Results: There is an extensive literature on atomoxetine; over 4000 children have participated in clinical trials of atomoxetine, demonstrating its short- and longer-term efficacy. In addition, studies have examined the moderating effect of comorbid disorders on atomoxetine response, as well as atomoxetine&amp;rsquo;s therapeutic potential for other psychiatric conditions. Short- and longer-term safety and tolerability continue to be reported.Conclusions: Atomoxetine is indicated for both acute and maintenance/extended treatment of pediatric ADHD. Clinicians and families must be familiar with atomoxetine&amp;rsquo;s evidence base, including its profile of clinical response and its possible effectiveness in the presence of comorbidity.Keywords: ADHD, atomoxetine, pediatri

hyperactivity disorder 10-year study of individuals with and without attention-deficit Cigarette smoking as a risk factor for other substance misuse: References Cigarette smoking as a risk factor for other substance misuse: 10-year study of individuals wi

Numerous studies have documented that attention-deficit hyperactivity disorder (ADHD) increases the risk for nicotine use across the life cycle. Milberger et al 1,2 found significant associations between ADHD and cigarette smoking in both referred and non-referred paediatric samples. Those studies documented that ADHD increased the risk for cigarette smoking in early adolescence twofold and was associated with a 2-year earlier age at onset than controls. Likewise, Tercyak et al 3 found that adolescents with ADHD were three times more likely to smoke than adolescents without ADHD. Pomerleau et al 4 documented that adult ADHD is associated with, and an increased risk for, tobacco addiction and, among smokers, increased difficulty quitting. Glass &amp; Flory 5 summarised several possible mechanisms for this relationship, including the self-medication hypothesis and other social, cognitive and psychopathological factors. The extant literature also supports an association between ADHD and other substance use disorders (alcohol or drug misuse or dependence) that establishes itself by mid to late adolescence. Milberger et al 6 showed that although non-nicotine substance use disorders were not associated with ADHD in early to midadolescence, they were significantly and robustly associated with ADHD by late adolescence. Using two 10-year follow-up studies of ADHD, Wilens and colleagues 7 found that ADHD was a significant risk factor for the development of substance use disorders and cigarette smoking in both genders. These findings bear remarkable congruence to results from retrospective studies of adults with and without ADHD that show that ADHD is associated with an increased risk for drug and alcohol misuse and dependence substance use disorders that tend to emerge in late adolescence and young adulthood. 207 Cigarette smoking as a risk factor for other substance misuse: 10-year study of individuals with and without attention-deficit hyperactivity disorder Joseph Biederman, Carter R. Petty, Paul Hammerness, Holly Batchelder and Stephen V. Faraone Background We previously documented that cigarette smoking is a risk factor for subsequent alcohol and drug misuse and dependence in adolescent girls with attention-deficit hyperactivity disorder (ADHD)

Risperidone treatment for ADHD in children and adolescents with bipolar disorder

Joseph Biederman, Paul Hammerness, Robert Doyle, Gagan Joshi, Megan Aleardi, Eric MickPediatric Psychopharmacology Research Department, Massachusetts General Hospital, Boston, MA, USAObjective: Children and adolescents with bipolar disorder are also at high risk of having comorbid attention-deficit hyperactivity disorder (ADHD). The objective of this study was to estimate improvement in ADHD symptoms in children with bipolar disorder.Methods: This was an open-label, study of risperidone monotherapy for the treatment of pediatric bipolar disorder. Thirty-one children and adolescents 4&amp;ndash;15 years of age (7.2 &amp;plusmn; 2.8 years) of both sexes (71%, N = 22 male) with pediatric bipolar disorder (YMRS score = 32.9 &amp;plusmn; 8.8) and ADHD (ADHD-RS score = 37.9 &amp;plusmn; 8.9) were included in these analyses.Results: Improvement in ADHD symptoms was contingent on improvement in manic symptoms. Although both hyperactive/impulsive (&amp;minus;7.5 &amp;plusmn; 5.5.6, p &amp;lt; 0.05) and inattentive (&amp;minus;6.8 &amp;plusmn; 5.0, p &amp;lt; 0.05) ADHD symptoms were significantly improved with risperidone, improvement was modest, and only 29% of subjects (N = 6) showed a 30% reduction in ADHD rating scale scores and had a CGI-I&amp;nbsp;&amp;le; 2.Conclusions: These results suggest that that treatment with risperidone is associated with tangible but generally modest improvement of symptoms of ADHD in children with bipolar disorder.Keywords: ADHD, bipolar disorder, children, risperidon