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1.
J Atten Disord ; 22(1): 14-24, 2018 Jan.
Article in English | MEDLINE | ID: mdl-25376194

ABSTRACT

OBJECTIVE: To evaluate children with ADHD and sleep problems with polysomnography (PSG) after guanfacine extended-release (GXR) administration. METHOD: Double-blind, randomized, placebo-controlled study was terminated early due to treatment-emergent concerns after enrolling 29 children aged 6 to 12 years. After >4 weeks dose adjustment and >1 week dose stabilization, 11 children received GXR and 16 controls underwent analyses with PSG. RESULTS: Although GXR improved ADHD symptoms, the primary outcome variable, total sleep time, was shorter in contrast to placebo (-57.32, SD = 89.17 vs. +31.32, SD = 59.54 min, p = .005). Increased time awake after sleep onset per hour of sleep was the primary factor for the reduction. Although rapid eye movement (REM), non-REM, and N3/slow wave sleep times were reduced, these were proportional to the overall sleep reduction. Sedation was common with GXR (73% vs. 6%). CONCLUSION: Morning-administered GXR resulted in decreased sleep and may contribute to sedation.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Attention Deficit Disorder with Hyperactivity/drug therapy , Guanfacine/administration & dosage , Adolescent , Adrenergic alpha-2 Receptor Agonists/adverse effects , Attention Deficit Disorder with Hyperactivity/complications , Child , Delayed-Action Preparations , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Early Termination of Clinical Trials , Female , Guanfacine/adverse effects , Humans , Male , Polysomnography , Psychiatric Status Rating Scales , Sleep/drug effects , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/psychology
2.
J Atten Disord ; 21(2): 110-119, 2017 01.
Article in English | MEDLINE | ID: mdl-24071772

ABSTRACT

OBJECTIVE: To examine efficacy and safety of adjunctive guanfacine extended release (GXR) on morning and evening ADHD symptoms using the Conners' Global Index-Parent (CGI-P) and Before-School Functioning Questionnaire (BSFQ). METHOD: Participants 6 to 17 years with ADHD ( N = 461) and suboptimal psychostimulant response were maintained on current psychostimulants and randomized to dose-optimized GXR (≤4 mg/d) in the morning (GXR AM) or evening (GXR PM), or placebo. RESULTS: CGI-P scores improved with GXR (morning assessment, GXR AM, placebo-adjusted least squares [LS] mean = -1.7, GXR PM = -2.6; evening assessment, GXR AM = -2.4, GXR PM = -3.0; all ps < .01). Parent-rated BSFQ scores reflected improved morning functioning with GXR (GXR AM, placebo-adjusted LS mean = -5.1; GXR PM = -4.7; both ps < .01). Most adverse events were mild or moderate. CONCLUSION: Adjunctive GXR AM or GXR PM was associated with improvements in morning and evening ADHD symptoms in children and adolescents.


Subject(s)
Adrenergic alpha-2 Receptor Agonists/administration & dosage , Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/administration & dosage , Guanfacine/administration & dosage , Adolescent , Adrenergic alpha-2 Receptor Agonists/adverse effects , Amphetamine/administration & dosage , Amphetamine/adverse effects , Analysis of Variance , Central Nervous System Stimulants/adverse effects , Child , Delayed-Action Preparations , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination , Female , Guanfacine/adverse effects , Humans , Male , Methylphenidate/administration & dosage , Methylphenidate/adverse effects , Parents , Schools , Treatment Outcome
3.
J Child Psychol Psychiatry ; 57(6): 770-1, 2016 06.
Article in English | MEDLINE | ID: mdl-27192956

ABSTRACT

Neuropsychiatric EEG-Based ADHD Assessment Aid (NEBA) is an EEG-based device designed to aid in the diagnostic process for ADHD by identifying individuals less likely to have ADHD by virtue of a lower theta/beta ratio. In using NEBA as an example, the Arns et al. commentary misstates the purpose of NEBA, which is to widen the differential rather than to make the diagnosis. Arns et al. caution about missing an ADHD diagnosis, but fail to mention the impact of overdiagnosis. If we are to advance our knowledge of the etiology and pathophysiology of ADHD, as well as develop tailored treatments and ultimately improve outcomes for ADHD, then biomarkers and objective assessment aids such as NEBA are needed to improve and refine diagnostic accuracy beyond symptom description and clinical history.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Electroencephalography , Humans , Marketing
4.
Brain Behav ; 5(4): e00330, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25798338

ABSTRACT

BACKGROUND: This study is the first to evaluate an assessment aid for attention-deficit/hyperactivity disorder (ADHD) according to both Class-I evidence standards of American Academy of Neurology and De Novo requirements of US Food and Drug Administration. The assessment aid involves a method to integrate an electroencephalographic (EEG) biomarker, theta/beta ratio (TBR), with a clinician's ADHD evaluation. The integration method is intended as a step to help improve certainty with criterion E (i.e., whether symptoms are better explained by another condition). METHODS: To evaluate the assessment aid, investigators conducted a prospective, triple-blinded, 13-site, clinical cohort study. Comprehensive clinical evaluation data were obtained from 275 children and adolescents presenting with attentional and behavioral concerns. A qualified clinician at each site performed differential diagnosis. EEG was collected by separate teams. The reference standard was consensus diagnosis by an independent, multidisciplinary team (psychiatrist, psychologist, and neurodevelopmental pediatrician), which is well-suited to evaluate criterion E in a complex clinical population. RESULTS: Of 209 patients meeting ADHD criteria per a site clinician's judgment, 93 were separately found by the multidisciplinary team to be less likely to meet criterion E, implying possible overdiagnosis by clinicians in 34% of the total clinical sample (93/275). Of those 93, 91% were also identified by EEG, showing a relatively lower TBR (85/93). Further, the integration method was in 97% agreement with the multidisciplinary team in the resolution of a clinician's uncertain cases (35/36). TBR showed statistical power specific to supporting certainty of criterion E per the multidisciplinary team (Cohen's d, 1.53). Patients with relatively lower TBR were more likely to have other conditions that could affect criterion E certainty (10 significant results; P ≤ 0.05). Integration of this information with a clinician's ADHD evaluation could help improve diagnostic accuracy from 61% to 88%. CONCLUSIONS: The EEG-based assessment aid may help improve accuracy of ADHD diagnosis by supporting greater criterion E certainty.


Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , Electroencephalography/methods , Adolescent , Biomarkers/analysis , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Male , Prospective Studies , United States
5.
J Child Adolesc Psychopharmacol ; 24(8): 435-41, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25286026

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the efficacy of once-daily guanfacine extended release (GXR) monotherapy administered either in the morning or evening, using a modified Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) assessed three times/day in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: This multicenter, double-blind, placebo-controlled study randomized children 6-12 years of age with ADHD into three groups: GXR a.m. (GXR in the morning and placebo in the evening), GXR p.m. (placebo in the morning and GXR in the evening), or twice-daily placebo. The CPRS-R:S, administered in the morning, afternoon, and evening prior to each study visit, was a secondary measure of efficacy. RESULTS: A total of 333 subjects were included in the analysis population (GXR a.m., n=107; GXR p.m., n=114; placebo, n=112). At visit 10, last observation carried forward (LOCF), subjects receiving GXR demonstrated significantly greater improvement from baseline in the daily mean CPRS-R:S total score, as well as in each of the morning, afternoon, and evening CPRS-R:S assessments, compared with placebo, regardless of the time of GXR administration (p<0.001 vs. placebo for GXR a.m. and GXR p.m.). In addition, subjects receiving GXR showed significantly greater improvements from baseline in each subscale score (oppositional, cognitive problems/inattention, hyperactivity, and ADHD index) compared with those receiving placebo, regardless of time of administration (p<0.003 vs. placebo across all subscales for GXR a.m. and GXR p.m.). CONCLUSIONS: These results provide further support for the demonstrated efficacy of once-daily GXR in reducing ADHD symptoms, and demonstrate that response is consistent throughout the day regardless of the time of administration, with improvement seen in ratings of oppositional as well as of ADHD symptoms.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Guanfacine/adverse effects , Child , Delayed-Action Preparations , Double-Blind Method , Drug Administration Schedule , Female , Guanfacine/therapeutic use , Humans , Male , Parents , Severity of Illness Index , Treatment Outcome
6.
J Am Acad Child Adolesc Psychiatry ; 51(1): 74-85.e2, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22176941

ABSTRACT

OBJECTIVE: To examine efficacy, tolerability, and safety of guanfacine extended release (GXR; ≤4 mg/d) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years of age with suboptimal, but partial, response to psychostimulant alone. METHOD: In this multicenter, 9-week, double-blind, placebo-controlled, dose-optimization study, subjects (N = 461) continued their stable dose of psychostimulant given in the morning and were randomized to receive GXR in the morning (GXR AM), GXR in the evening (GXR PM), or placebo. Efficacy measures included ADHD Rating Scale IV (ADHD-RS-IV) and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events (AEs), vital signs, electrocardiograms, and laboratory evaluations. RESULTS: At endpoint, GXR treatment groups showed significantly greater improvement from baseline ADHD-RS-IV total scores compared with placebo plus psychostimulant (GXR AM, p = .002; GXR PM, p < .001). Significant benefits of GXR treatment versus placebo plus psychostimulant were observed on the CGI-S (GXR AM, p = .013; GXR PM, p < .001) and CGI-I (GXR AM, p = .024; GXR PM, p = .003). At endpoint, small mean decreases in pulse, systolic, and diastolic blood pressure were observed in GXR treatment groups versus placebo plus psychostimulant. No new safety signals emerged following administration of GXR with psychostimulants versus psychostimulants alone. Most AEs were mild to moderate in severity. CONCLUSIONS: Morning or evening GXR administered adjunctively to a psychostimulant showed significantly greater improvement over placebo plus psychostimulant in ADHD symptoms and generated no new safety signals. Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants; http://www.clinicaltrials.gov; NCT00734578.


Subject(s)
Adrenergic alpha-Agonists/administration & dosage , Adrenergic alpha-Agonists/adverse effects , Attention Deficit Disorder with Hyperactivity/drug therapy , Guanfacine/administration & dosage , Guanfacine/adverse effects , Adolescent , Central Nervous System Stimulants/therapeutic use , Child , Delayed-Action Preparations , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Male , Placebos , Psychiatric Status Rating Scales , Severity of Illness Index , Treatment Outcome
7.
Neuropsychiatr Dis Treat ; 3(3): 293-301, 2007 Jun.
Article in English | MEDLINE | ID: mdl-19300563

ABSTRACT

Modafinil, a wakefulness-promoting agent unrelated to classical sympathomimetic stimulants, has been studied in a total of 933 children and adolescents as a treatment for attention-deficit/hyperactivity disorder (ADHD). Several studies, including three double-blind, placebo-controlled studies with intent-to-treat analyses, have demonstrated the efficacy of modafinil film-coated tablets in reducing symptoms of ADHD and associated problem behaviors in children and adolescents. Modafinil is generally well tolerated, with adverse events (such as insomnia, headache, loss of appetite, weight loss, and gastrointestinal discomfort) that are generally mild to moderate, rarely leading to medication discontinuation. To minimize treatment-emergent side effects, titration to the target dose of 355-425 mg once a day should take place over 2-3 weeks. Due to reports of skin rash (including one case of possible erythema multiforme/Stevens Johnson Syndrome during pivotal studies), additional studies have been requested to better evaluate the risks of developing severe cutaneous adverse reactions.

8.
J Am Acad Child Adolesc Psychiatry ; 45(5): 503-511, 2006 May.
Article in English | MEDLINE | ID: mdl-16601402

ABSTRACT

OBJECTIVE: To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD). METHOD: In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global Impression of Improvement (CGI-I) scale. RESULTS: Two hundred patients were randomized. Modafinil produced significant reductions in ADHD-RS-IV total scores at school (n = 128; mean change +/- SD: -17.5 +/- 13.1 points) compared with placebo (n = 66; -9.7 +/- 10.3 points; p < .0001). Similarly, modafinil reduced ADHD-RS-IV total scores at home compared with placebo (-17.6 +/- 13.3 versus -7.5 +/- 11.8 points; p < .0001). Fifty-two percent of patients randomized to modafinil and 18% of those randomized to placebo met prestudy criteria for responder on the CGI-I (p < .0001). Randomization to modafinil was associated with significantly more insomnia, headache, decreased appetite, and weight loss than randomization to placebo, but discontinuation attributed to adverse events did not differ statistically between treatment groups (modafinil, 5%; placebo, 6%). CONCLUSION: Modafinil was well tolerated and reduced ADHD symptoms at school and home compared with placebo.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Benzhydryl Compounds/administration & dosage , Central Nervous System Stimulants/administration & dosage , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Benzhydryl Compounds/adverse effects , Central Nervous System Stimulants/adverse effects , Child , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Modafinil , Patient Acceptance of Health Care , Personality Assessment , Tablets , Treatment Outcome
9.
J Child Neurol ; 20(7): 603-10, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16159529

ABSTRACT

Despite few supportive data, aripiprazole was being administered to children and adolescents for management of mood instability, aggression, and psychosis. Using a retrospective review (n = 11) and prospective recruitment (n = 6), 17 children and adolescents received aripiprazole 5 to 20 mg/day. Only 4 of 16 bipolar and autistic subjects (25%) demonstrated reduced aggression without adverse events, and the symptoms of 2 of 4 psychotic subjects improved. Coadministration of sedative medications (particularly guanfacine or clonidine) and weight < 58 kg increased the risk of adverse events, such as increased lability and aggression. All three children < 8.6 years old, all four children < 34 kg, and all five children receiving alpha2-agonists developed adverse events prior to clinical efficacy. Age > 11 years, weight > 58 kg, and absence of sedative medications were associated with a 56% (five of nine) success rate. Until larger, prospective studies are completed, caution is advised when considering aripiprazole for smaller children and children receiving sedative medications.


Subject(s)
Antipsychotic Agents/therapeutic use , Attention Deficit and Disruptive Behavior Disorders/prevention & control , Bipolar Disorder/psychology , Child Behavior Disorders/drug therapy , Child Behavior Disorders/psychology , Piperazines/therapeutic use , Quinolones/therapeutic use , Adolescent , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Aripiprazole , Attention Deficit and Disruptive Behavior Disorders/etiology , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Male , Piperazines/administration & dosage , Piperazines/adverse effects , Prospective Studies , Quinolones/administration & dosage , Quinolones/adverse effects , Retrospective Studies , Treatment Outcome , Treatment Refusal
10.
Pediatr Neurol ; 29(5): 440-4, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14684241

ABSTRACT

Valproic acid and its derivatives are commonly administered antiepileptic drugs for children and adults. Five residents at a children's long-term care facility manifested hypoalbuminemia while being administered divalproex, although serum liver function test results and urinalysis results were normal. When the patients were free from valproic acid, the serum albumin levels increased into the normal range (17-30% higher than the serum albumin levels while patients were receiving valproic acid) despite the absence of any dietary changes. Comparing the serum albumin levels for eight residents who received divalproex (3.1 gm/dL +/- 0.4 gm/dL) with the serum albumin levels for 13 residents who were not receiving valproic acid or its derivatives (3.8 gm/dL +/- 0.2 gm/dL), the difference was significant (P < 0.001). This difference could not be accounted for by nutritional, environmental, laboratory, or urinary causes. In this study, divalproex administration was a contributing factor in the development of reversible hypoalbuminemia in this population of severely disabled, neurologically injured children and young adults. Further studies are required to determine the exact etiology and clinical significance of valproate-mediated hypoalbuminemia.


Subject(s)
Anticonvulsants/adverse effects , Hypoalbuminemia/chemically induced , Valproic Acid/adverse effects , Adult , Child , Child, Preschool , Female , Humans , Male , Seizures/drug therapy , Serum Albumin/metabolism , Valproic Acid/therapeutic use
11.
Pediatr Neurol ; 29(2): 136-42, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14580657

ABSTRACT

Previous clinical evidence suggested that modafinil may improve clinical features of children with attention-deficit hyperactivity disorder. To test this hypothesis, a randomized, double-blind, placebo-controlled study design was used. Of 24 children initially randomized into the study, 11 control subjects and 11 treatment patients completed the study, with evaluation before medication and after 5 to 6 weeks. The average Test of Variables of Attention attention-deficit hyperactivity disorder z score improved by 2.53 S.D.s for the modafinil group compared with a decline of 1.02 for control patients (P < or = 0.02). Conners Rating Scales ADHD total t scores for the modafinil group improved from 76.6 to 68.2 compared with improvement from 77.7 to 76.0 for control subjects (P = 0.04). Ten of 11 treatment patients were reported as "significantly" improved, whereas eight of 11 control subjects were reported as manifesting "no" or "slight" improvement (P < 0.001). Adverse effects were few and manageable, with no anorexia. Modafinil may be a useful treatment for children with ADHD, particularly when anorexia limits use of stimulants.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Benzhydryl Compounds/therapeutic use , Central Nervous System Stimulants/therapeutic use , Adolescent , Attention Deficit Disorder with Hyperactivity/psychology , Benzhydryl Compounds/adverse effects , Central Nervous System Stimulants/adverse effects , Child , Double-Blind Method , Female , Humans , Male , Modafinil , Neuropsychological Tests , Surveys and Questionnaires
12.
J Dev Behav Pediatr ; 23(4): 225-30, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12177568

ABSTRACT

The objectives of this study were to determine whether autistic children taking levetiracetam (1) showed improvement in the areas of aggression, impulsivity, hyperkinesis, and mood instability, and (2) showed a nootropic response. Ten white autistic boys ranging from 4 to 10 years were compared pretreatment and while taking levetiracetam for an average of 4.1 weeks. Inattention, hyperkinesis, and impulsivity were evaluated using the Achenbach Attention Problems scale, Conners DSM-IV Total scale, and the Conners Attention-Deficit Hyperactivity Disorder Index scale, all of which showed statistically significant improvements. Mood instability was measured with the Conners Global Index (CGI) Emotional Lability and CGI Total scales, both of which showed statistically significant improvements. Aggressive behavior, as measured with the Achenbach Aggression scale, showed statistically significant improvement only for subjects who were not recently weaned from medications that reduce aggression (e.g., risperidone, carbamazepine, desipramine). Levetiracetam may reduce hyperactivity, impulsivity, mood instability, and aggression in autistic children with these problems. No nootropic effect was observed.


Subject(s)
Autistic Disorder/drug therapy , Nootropic Agents/therapeutic use , Piracetam/analogs & derivatives , Piracetam/therapeutic use , Aggression , Anticonvulsants/therapeutic use , Autistic Disorder/psychology , Cetirizine/therapeutic use , Child , Child Behavior Disorders/epidemiology , Child Behavior Disorders/etiology , Child, Preschool , Disruptive, Impulse Control, and Conduct Disorders/epidemiology , Disruptive, Impulse Control, and Conduct Disorders/etiology , Drug Therapy, Combination , Histamine H1 Antagonists/therapeutic use , Humans , Hyperkinesis/epidemiology , Hyperkinesis/etiology , Incidence , Levetiracetam , Male , Prospective Studies , Surveys and Questionnaires , Valproic Acid/therapeutic use
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