Pediatric Psychopharmacology Research Articles

In Model of Anorexia Etiology, Dieting Is ‘Engraved’ in Brain

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessIn Model of Anorexia Etiology, Dieting Is ‘Engraved’ in BrainMark MoranMark MoranSearch for more papers by this authorPublished Online:20 Jul 2012https://doi.org/10.1176/pn.47.14.psychnews_47_14_14-aAbstractPersistent dieting associated with anorexia nervosa (AN) may be a learned habit that becomes ingrained over time and extraordinarily difficult to break in adults who have had the disorder for many years.Timothy Walsh, M.D.Photo: David HathcoxSo suggested Timothy Walsh, M.D., Ruane Professor of Pediatric Psychopharmacology at Columbia University, in a lecture at APA’s annual meeting in Philadelphia in May titled “The Persistent Enigma of Anorexia Nervosa.”Walsh proposed a new conceptual model that attempts to explain why compulsive dieting—despite its potentially deadly consequences—is remarkably durable. Drawing on learning theory, Walsh suggested that dieting, initially rewarding, becomes a fixed habit that occurs automatically and involves a structured behavioral sequence prone to be elicited by a range of stimuli.“Research has worked out to an impressive degree how humans learn behavior patterns and how those patterns turn into habits,” Walsh said. “What I have learned from studying that research is that humans pick up a new behavior because it is rewarding. But if you over-train the behavior, in time a person will continue the behavior even when the reward is not consistently received.”He said that during adolescence several factors—including the cultural emphasis on thinness among women—make persistent dieting that leads to thinness rewarding and thereby “overtrain” the brain. “Over time the behavior becomes engraved on the brain,” Walsh said. “It’s this that makes it so hard to eradicate.”Walsh also reviewed proposed changes to criteria for anorexia nervosa in DSM-5. These include editorial changes to existing criteria related to body weight and “fear of getting fat.”Walsh said there are patients who meet all criteria for anorexia nervosa but do not explicitly acknowledge a fear of getting fat, so the newly proposed criteria say “Intense fear of gaining weight or becoming fat or persistent behavior that interferes with weight gain, even though at a significantly low weight.”But the most significant proposal to the AN diagnostic criteria is elimination of amenorrhea as a requirement for diagnosis. In an interview with Psychiatric News for a report on proposed changes to DSM-5 criteria, Walsh said, “A literature review yielded a body of research showing that women who meet all the criteria for anorexia nervosa but still report some menstrual activity are virtually identical in terms of clinical impairment and treatment response” (Psychiatric News, January 6).In his annual meeting lecture, Walsh also reviewed data on treatment efficacy. He noted that a large body of research now supports the efficacy of the so-called “Maudsley method.”According to the Web site Maudsley Parents (www.maudsleyparents.org) the therapy is “an intensive outpatient treatment where parents play an active and positive role to help restore their child’s weight to normal levels expected given their adolescent’s age and height, then hand control over eating back to the adolescent and encourage normal adolescent development through an in-depth discussion of these crucial developmental issues as they pertain to their child.”Walsh presented data from several studies showing higher rates of full and partial recovery using the Maudsley method rather than traditional individual therapy.Yet he noted that there are not comparably effective treatments for adults. “Youngsters who develop AN, especially if they get a Maudsley intervention, do generally well over time. In contrast, on average, the treatment of older people who have had the disease longer—even only five or 10 years longer—is much more challenging and difficult.“We don’t have treatments for adults anywhere near as good as we have for adolescents,” he said. “The question that I have been led to wonder about is how once this disorder gets established, it becomes so persistent and so refractory to treatments that you would think would be more effective than they are.”Walsh said the model of AN as a learned behavior helps explain why teenagers who are treated for the disorder do so much better than adults. “As teenagers they have had less time to practice the habit, so it is less well established and less engraved in neural circuits,” he said. To watch the video of Walsh, go to www.youtube.com/watch?v=9d0l-0i4IPQ. ISSUES NewArchived

High Rate of Non-Eligibility: Methodological Factors Impacting on Recruitment for a Multicentre, Double-Blind Study of Paediatric Patients with Major Depressive Disorder

This report describes difficulties encountered when attempting to recruit children and adolescents with major depression for a recent international double-blind, placebo-controlled trial (www.clinicaltrials.gov Nr. NCT00849901). Over a 14-month period, children and adolescents with depressive symptoms were pre-screened for their eligibility for inclusion. 85 patients (age 7-17 years) were considered. Of these, only one was enrolled. The main reasons for non-eligibility were: failure to meet the baseline severity criterion on the primary outcome scale (clinical global impression-severity; 32.1% of the patients); requirement for immediate hospitalisation (15.4%); or the presence of an exclusionary comorbid psychiatric disorder (19.1%). The recruitment of paediatric patients with major depression was primarily limited by various inclusion and exclusion criteria. Slow recruitment of small patient samples may impact strongly on the representativeness and generalisability of research findings, and thus on analyses in evidence-based medicine and on the development and recommendations of treatment guidelines. This may impact in turn on the feasibility of the clinical development and registration process of new compounds in paediatric psychopharmacology and beyond.

The use of Clonidine outside its licensed indication in paediatric psychopharmacology: a UK survey of current practice

<h3>Aims</h3> To ascertain current practice, experience and opinion among UK clinicians of the use of Clonidine for the treatment of conditions such as tics and behavioural disturbances, with particular focus on sleep problems. <h3>Methods</h3> Electronic survey sent to all Child and Adolescent Psychiatrists (CAPs) and Paediatricians in selected specialties. 389 respondents (116 Paediatricians, 273 CAPs). <h3>Results</h3> 172 (44%) respondents prescribed Clonidine in the last year, most commonly for (in decreasing order of frequency) tic disorders, sleep problems, hyperactivity and aggression. CAPs were more likely to prescribe for hyperactivity; Paediatricians for sleep problems. Patient numbers ranged from 0-100 with Paediatricians having the largest caseloads. Over 90% practised in line with NICE attention deficit hyperactivity disorder (ADHD) guidelines regarding initial physical/cardiovascular examination, but not in the use of electrocardiograms. After initiation, 78% monitored blood pressure. The majority reported a good level of short-term effectiveness in tics, sleep and hyperactivity, but some reduction in effect in long-term use, especially for sleep. 59% experienced drug tolerance which had an impact on ultimate efficacy. Adverse effects, reported by 54%, were generally considered mild. 53 respondents (31%) prescribed for a range of sleep problems including movement disorders, for children aged 2-18 years, predominately with neurodevelopmental disorders. 94% reported using drugs as second line treatment. Initiation dose, titration regime and maximum doses showed considerable variation but within the broad parameters described in the literature. In general, there were no significant differences in practice evident between Paediatricians and CAPs. 272 respondents had not prescribed Clonidine, not managing relevant conditions, not knowing how to use it or because of concerns about safety or effectiveness. Despite this, 92% of all respondents said they would find clinical guidelines helpful for their practice. <h3>Conclusion</h3> There is a lack of rigorous evidence for tics and behaviour and only anecdotal evidence for sleep. This survey suggests: The use of Clonidine by both professions is mostly appropriate, albeit on the basis of limited evidence. A lack of knowledge about a potentially useful drug for which clinical guidelines would be helpful. A need for properly constructed, large scale, randomised controlled trials for Clonidine, particularly in sleep disorders.

Development of a Child Psychopharmacology Trial Scale

Psychotropic prescriptions for children and adolescents are on the rise. Until recently, pediatric psychopharmacology practice was extrapolated from adult data. While over 70% of pediatric psychopharmacology prescriptions were “off label”, evidence grew of differences between pediatric and adult biological properties and psychosocial factors. Spurred by recent U.S. Congressional legislation, there have been many newly published studies on safety, tolerability, and efficacy for medications in children and adolescents. Traditional methods for clinicians to evaluate these trials are qualitative, confusing to many, difficult to use as a comparison between studies, and do not account for important issues specific to the pediatric population. This paper describes the initial development of the Child Psychopharmacology Trial Scale (CPTS). A Medline review of the past 20 years on scale development along with interviews with expert psychopharmacologists and scale developers were conducted. A thorough yet concise scale was developed and tested in a pilot study to assess for feasibility. This one-page scale is presented. The CPTS provides 1) a standard evaluation of appropriate study design, 2) a confidence index for the clinician who wants to base his/her drug selection from available pediatric studies, 3) a standard to compare among studies, and 4) an effort to promote better science in pediatric trials. The CPTS has good face validity. Results will aid further development. It is to our knowledge the first attempt to quantify the quality of studies in the field of pediatric psychopharmacology. Keywords: Evaluation, medication, pediatrics, psychopharmacology, scale, trial, randomization, Extensions, Child Psychopharmacology, Anxiety, Hyperactivity, Mental Health, suicidal, tolerability, filtration

P-350 - Training Resident Physicians in Pediatric Psychopharmacology for ADHD

Children and adolescents experience significant emotional disorders and the prevalence of these conditions is notable. There is a dearth of pediatric mental health care professionals in the U.S., and among those professionals available, geographic and reimbursement limitations restrict access to the care. Primary health care providers are being encouraged to provide some of the identification and care management to offset this access problem. Expand clinical skills of pediatric providers through enhanced training of residents in the use of psychopharmaceuticals for the most common psychiatric diagnosis in U.S. children (ADHD). Second- and third-year pediatric residents attended an intensive 10-hour training in pediatric psychopharmacology for ADHD in 2010. The curriculum was based on a well-established 3-day program that teaches primary care clinicians the elements of guideline-level care for common behavioral health conditions. The program included pre- and post- training assessment of resident knowledge of current practice guidelines for ADHD and intention to use them. Special attention was given to proper use of screening instruments, diagnostic scales, treatment options, importance of medication options and increased frequency of visits during drug initiation and titration of dosages, and obstacles to implementation. Results showed significant and sometimes large post-training increases in intentions to use medication therapies, systematic progression through stimulant and non-stimulant alternatives, parent and teacher symptom rating scales throughout treatment, and side effect scales during dose titration. A one-day enhanced training program improved knowledge of, attitudes toward, and intention to use guidelines of care for youth with ADHD.

Paliperidone Palmitate in a Child with Autistic Disorder

To the Editor: Autistic disorder (autism) is a neuropsychiatric disorder characterized by impairments in social interaction, communication, and stereotyped behaviors and interests (American Psychiatric Association 2000). Individuals with this disorder often exhibit associated interfering symptoms including irritability, hyperactivity, and inattention. Irritability, defined as aggression, severe tantrums, and self-injury, is a particularly limiting symptom with the capacity to diminish the quality of life for both the affected individual and their caregivers. Historically, antipsychotics have been the pharmacologic treatment of choice for irritability in youth with autism. Early research focused on typical antipsychotics such as haloperidol (Cohen et al. 1980; Anderson et al. 1984). Atypical antipsychotics have a lower rate of side effects such as dyskinesias and are currently considered first-line choice for treatment of irritability associated with autistic disorder (Erickson et al. 2007; Blankenship et al. 2010). Both risperidone and aripiprazole were approved by the U.S. Food and Drug Administration (FDA) to treat irritability in youth with autism aged 5–16 and 6–17 years, respectively. Multiple double-blind, placebo-controlled studies have demonstrated the efficacy of risperidone (Research Units on Pediatric Psychopharmacology Autism 2002; Shea et al. 2004) and aripiprazole (Marcus et al. 2009; Owen et al. 2009) for the treatment of this symptom domain. Paliperidone is the active metabolite of risperidone and was approved by FDA to treat schizophrenia and schizoaffective disorder in adults. Stigler et al. (2010) recently described the effectiveness of paliperidone in treating irritability in two individuals with autism. A 16-year-old female patient and a 20-year-old male patient, both diagnosed with autism, were treated with paliperidone (3 and 12 mg/day, respectively) after they demonstrated a lack of adequate improvement on other medication regimens. Both were judged to have significant improvement in their symptoms, including aggression and tantrums, with paliperidone treatment. No adverse events were reported. Both individuals lost weight and experienced improvements in their fasting lipid profiles while taking paliperidone. In 2009, the FDA approved a sustained-release intramuscular (IM) formulation of paliperidone, paliperidone palmitate, for the treatment of adults with schizophrenia. In this report, we demonstrate the successful use of paliperidone palmitate for the treatment of irritability in a child with autism who was unable to tolerate oral medications.

Journal Digest

Journal Digest

Predictors and Moderators of Parent Training Efficacy in a Sample of Children with Autism Spectrum Disorders and Serious Behavioral Problems

The Research Units on Pediatric Psychopharmacology--Autism Network reported additional benefit when adding parent training (PT) to antipsychotic medication in children with autism spectrum disorders and serious behavior problems. The intent-to-treat analyses were rerun with putative predictors and moderators. The Home Situations Questionnaire (HSQ) and the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist were used as outcome measures. Candidate predictors and moderators included 21 demographics and baseline measures of behavior. Higher baseline HSQ scores predicted greater improvement on the HSQ regardless of treatment assignment, but no other predictors of outcome were observed. None of the variables measured in this study moderated response to PT. Antipsychotic medication plus PT appears to be equally effective for children with a wide range of demographic and behavioral characteristics.

Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors

Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors

Escalas y cuestionarios pragmáticos en psicofarmacología pediátrica: ¿estamos haciendo lo correcto?

Recent changes in legislation have stimulated a new wave of interest and activity in paediatric psychopharmacology. This increased activity has coincided with a recognition that pragmatic measures of outcome such as those that tap into impairment and health related quality of life (HRQOL) have the potential to add considerably to the traditional symptom based measures of outcome. There are however considerable methodological issues associated with these types of measure, and these are made more complex when they are applied in mental health and paediatric settings. There is a clear need for the continued development of valid and reliable measures of HRQOL and impairment that are fit for purpose for use in clinical trials. Other more specific issues that need to be considered, and which all require further investigation include those relating to; age, self versus proxy ratings, contextual issues, generic versus disorder specific measures and definitions of clinically meaningful change. Most of the child and adolescent mental health trials that have included pragmatic measures have been conducted in attention-deficit/hyperactivity disorder (ADHD) samples, have been industry sponsored, use only parent ratings and focus on one drug (atomoxetine). Taken together they do however suggest that pharmacological treatments can impact positively on impairment and HRQOL, although with smaller effect sizes than is seen for symptom reduction. Further studies, across a wider range of disorders and treatments with multiple measures and multiple raters, are to be encouraged. In addition to reporting the basic outcomes from these studies researchers should use these data to improve the measurement models and refine both the measures and the trial designs.

Nouveaux enjeux de la recherche clinique en psychopharmacologie chez l’enfant et l’adolescent

A large proportion of medicines used in children are actually prescribed off-label, which can place children at a direct risk of under- or overdosing and a delayed risk of long-term adverse effects, and children have often been denied access to new or innovative medications. Many generations of paediatricians and other physicians have learned to live with the situation. But because such situation is nowadays considered as unethical, the need to obtain paediatric information for medicines used in children seems a matter of consensus on a global basis. If the therapeutic effects of amphetamines in hyperactive children were first described in 1937, thus, preceding the major discoveries of adult psychopharmacology, since this little innovation has occurred in paediatric psychopharmacology. However, it is widely recognized that mental disorders in children and adolescents lead to a major burden for them and for their families. Over the past decade, under the impulsion of the US paediatric legislation, the number of high quality paediatric psychopharmacological studies has dramatically increased. Like what happened in the US, it was clear in European Union, that there was a need for a legal obligation for Pharmaceutical Companies to perform studies in paediatric populations, and a new Paediatric European Regulation came into force in 2007, opening a new era in the history of European regulation with the ambition of improving the health of children and adolescents. Therefore drug development is changing; the concern of protecting children against clinical research fading away, a new paradigm is now emerging, i.e. protecting children through clinical research. In Europe, paediatric development is no longer an option but needs to be truly integrated in clinical development plans with paediatric evaluations being a regular part of every drug development process. It seems reasonable to anticipate that more research may occur as well in paediatric psychopharmacology and more studies will be enrolling paediatric patients all over the world in the forthcoming years. But paediatric clinical development is difficult and the hurdles of conducting clinical trials in paediatric population are numerous. This article presents briefly the new European Paediatric Regulation, illustrates its purpose through the example of antidepressants in children and adolescents, and discusses new research challenges in paediatric psychopharmacology. Ultimately, it is through well-conducted research that children will gain access to new medications and receive safe and optimal drug therapy.

Design and Subject Characteristics in the Federally-Funded Citalopram Trial in Children with Pervasive Developmental Disorders

The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 (±3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger's Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials.

Priority Mental Health Disorders of Children and Adolescents in Primary-care Pediatric Settings in India 2: Diagnosis, Pharmacological Treatment and Referral

The advent of pediatric psychopharmacology has enormously improved psychiatric care of children and adolescents. Nonetheless, our practice of diagnosis, treatment and referral in primary-care pediatric settings is not optimum as current evidence based knowledge is not regularly applied in the actual clinical circumstances. To help primary-care pediatricians minimise this in research-clinical practice, pharmacological treatment and referral in their clinical practice, they need to follow a two-tier diagnostic and multi axial treatment approach. The two-tier diagnostic approach of using a screening measure followed by confirmation of the screen positive cases with reference standard clinical criterion, improves the sensitivity and specificity. The multiaxial treatment has the advantage of offering a holistic approach to the intervention and improve prognosis from the interacting axes. The primary-care physician should be aware of the medications of choice for the Priority Mental Health Disorders and their drug interactions. Finally, referral of cases with atypical presentations, multiple comorbidities and poor response to the first-line of treatment needs referral to the next tier in the system.

Developments in Pediatric Psychopharmacology

Most major psychiatric disorders have an onset in childhood or adolescence in a sizeable proportion of patients, and earlier onset disorders often have a severe and chronic course that can seriously disrupt sensitive developmental periods, with lifelong adverse consequences. Accordingly, psychopharmacologic treatments have been increasingly utilized in severely ill youth. However, the increased use of psychopharmacologic treatments in pediatric patients has also raised concerns regarding a potential overdiagnosis and overtreatment of youth, without adequate data regarding the pediatric efficacy and safety of psychotropic agents. Over the past decade, a remarkable number of pediatric randomized controlled trials have been completed, especially with psychostimulants, antidepressants, and antipsychotics. For these frequently used agents, effect sizes against placebo have typically been at least moderate, with most numbers-needed-to-treat well below 10 for response, indicating clinical significance as well. Nevertheless, data also point to a greater and/or different profile of susceptibility to adverse effects in pediatric compared to adult patients, as well as to a role for nonpharmacologic treatments, given alone or combined with pharmacotherapy, for many of the youth. Taken together, these results highlight the need for a careful assessment of the risk-benefit relationship of psychopharmacologic treatments in patients who cannot be managed sufficiently with nonpharmacologic interventions and for routine, proactive adverse effect monitoring and management. Although considerable progress has been made, there is still enormous need for additional data and funding of pediatric psychopharmacology trials. It is hoped that the field will acquire the necessary resources to propel pediatric clinical psychopharmacology to new levels of insight by linking it with, but not replacing it by, pharmacoepidemiologic and biomarker approaches and advances.

S10-04 - Evidence-based training in treatment treatments: The case of pediatric psychopharmacology

IntroductionDespite major research advances in pediatric psychopharmacology and psychotherapy over the last 20 years, the lack of well-trained specialists has posed almost insurmountable barriers to many children and families from receiving high-quality, evidence-based assessment and treatments. The REACH Institute, an international non-profit organization dedicated to disseminating evidence-based treatments, has developed portable, effective methods to train primary care and specialty health providers in pediatric psychopharmacology and psychotherapies.ObjectivesTo develop effective, scientifically-proven methods for teaching and disseminating evidence-based treatments.AimsTo develop, disseminate, and evaluate high quality approaches for teaching primary care and specialty mental health practitioners in pediatric psychopharmacology.MethodsUsing novel approaches grounded in scientific behavioral change technologies, over 700 health care providers have been trained in evidence-based pediatric psychopharmacology in sites across multiple countries, including the US, Canada, and Norway. All trainings are rigorously evaluated for changes in health care practitioners' behaviors and clinical practices, including within an NIH-funded randomized controlled trial (RCT).ResultsTrainings have been very well-received across multiple countries, requiring only minor adaptations. These trainings have been effective in yielding changes in health care practitioners abilities and actual clinical practices, enabling more children to access appropriate pediatric psychopharmacology.ConclusionsEffective and disseminable methods for changing health care practitioners behaviors in applying pediatric psychopharmacology treatments are possible, and can be adapted to different countries, languages, and cultural contexts.

Ethical, clinical and practical considerations in designing clinical trials in pediatric psychopharmacology

Since the beginning of this new century, drug development is changing; the concern of protecting children against clinical research is fading away and a new paradigm, which is not yet necessarily accepted by all of society, is now emerging; that of protecting children through clinical research. It is unethical to withold available treatments from children because of lack of research, consequently it is expected that the number of pediatric clinical trials will increase in the future. However, research is not deprived of risks, and it is necessary to maintain a perfectly well-balanced, scientific and ethical approach when designing pediatric clinical trials. Child psychopharmacology provides an opportunistic paradigm of the difficulties and challenges of pediatric drug development. The hurdles of developing and conducting research in the pediatric population are numerous and some of them are more exacerbated in the field of child and adolescent psychiatry than in other pediatric areas such as pediatric onc...

Aggression, ADHD symptoms, and dysphoria in children and adolescents diagnosed with bipolar disorder and ADHD

BackgroundThis study had two objectives: (1) examine characteristics of aggression in children and adolescents diagnosed with bipolar disorder and (2) determine whether the CBCL pediatric bipolar disorder profile differentiated youngsters with bipolar disorder from youngsters with ADHD. MethodChildren and adolescents referred to a pediatric psychopharmacology clinic were systematically evaluated for psychopathology using a psychiatrist-administered diagnostic interview, parent- and teacher-report rating scales assessing the child's behavior, and child-completed self-report scales. In this sample, 27 children and adolescents were diagnosed with bipolar disorder and 249 youngsters were diagnosed with ADHD without co-occurring bipolar disorder. These two groups were compared to determine whether there were significant differences on various measures of psychopathology. ResultsYoungsters diagnosed with bipolar disorder were more verbally aggressive and exhibited higher levels of reactive aggression than youngsters with ADHD without co-occurring bipolar disorder. Youngsters with bipolar disorder also reported higher levels of depressive symptoms than youngsters with ADHD without bipolar disorder. The CBCL pediatric bipolar disorder profile did not accurately identify youngsters diagnosed with bipolar disorder. ConclusionsThe present findings present a picture of manic youngsters as verbally aggressive and argumentative, who respond with anger when frustrated. Youngsters diagnosed with bipolar disorder and ADHD exhibited significant levels of impulsive behavior and attention problems, but youngsters with bipolar disorder also exhibited significant levels of aggressive behavior and dysphoric mood. Finally, the CBCL pediatric bipolar disorder profile did not accurately identify youngsters who were diagnosed with bipolar disorder.

Tolerability of atomoxetine for treatment of pediatric attention-deficit/hyperactivity disorder in the context of epilepsy

To examine atomoxetine's tolerability in patients with epilepsy, we reviewed medical records of all patients with epilepsy who were treated with atomoxetine in a tertiary care pediatric psychopharmacology practice. Twenty-seven patients (10.1±4.2years, 63% male) with an average seizure frequency at baseline of 7±24 per month (median: 0, range: 0–90) were found. Symptoms of attention-deficit/hyperactivity disorder in twenty-five patients (92.5%) had previously not responded to stimulants. Atomoxetine, average dose 35.2±24.4mg, was given for a median of 26weeks (range: 4–141). Seventeen patients (63%) discontinued atomoxetine due to: inadequate response (n=7, 26%), worsening behavior such as increased irritability/activation (n = 7, 26%), nonadherence (n=1, 4%), emerging psychotic-like symptoms (n=1, 4%), and appetite decrease and tremor (n=1, 4%). There were no discontinuations because of seizure exacerbation. Atomoxetine dose, epilepsy etiology, seizure type, and comorbid psychiatric disorders did not predict discontinuation. No safety problems of sufficient magnitude to preclude prospective studies of atomoxetine in children with epilepsy were found.

The Utility of Clinicians Ratings of Anxiety Using the Pediatric Anxiety Rating Scale (PARS).

Clinician ratings of anxiety hold the promise of clarifying discrepancies often found between child and parent reports of anxiety. The Pediatric Anxiety Rating Scale (PARS) is a clinician-administered instrument that assesses the frequency, severity, and impairment of common pediatric anxiety disorders and has been used as a primary outcome measure in several landmark treatment trials. However, no data on nonanxious youth have been published. The purpose of this study was to address this gap by examining clinician's ratings of anxiety on the PARS in a volunteer sample of youth without anxiety disorders (n = 84; ages 7-12; 51% female, 75% Caucasian). The nonanxious sample was comprised of youth with (At-risk; n = 36) and without (Healthy; n = 48) anxious parents. Data were also used to evaluate the reliability (i.e., internal consistency), convergent, and divergent validity of the clinician-rated PARS. In addition, a receiver operating curve analysis was used to determine optimum cut off scores indicative of clinical levels of anxiety by comparing PARS scores between these nonanxious youth and a clinically anxious sample (n = 77) randomized in the Research Units of Pediatric Psychopharmacology (RUPP) anxiety study (RUPP 2001). Results indicated that anxious and nonanxious youth were significantly different on all PARS severity items. Optimum cutoff scores of 11.5 (5-item total score) and 17.5 (7-item total score) discriminated youth with and without anxiety disorders. Cronbach alphas for the Healthy and At-risk sample were .90 and .91 and .75 and .81 for the 5- and 7-item total PARS scores respectively, supporting the measure's internal consistency among nonanxious youth. PARS total scores were positively correlated with other measures of anxiety (i.e., the Screen for Child Anxiety Related Emotional Disorders) for the At-risk but not Healthy subsample. PARS scores were not significantly correlated with depressive symptoms (i.e., Children's Depression Inventory). Overall, findings support the utility of clinician's assessments of anxiety symptoms for nonanxious youth. Using the PARS can help facilitate determining whether a child's anxiety level is more similar to those with or without an anxiety disorder.

Cognitive Development in Adults With Attention-Deficit/Hyperactivity Disorder

This study evaluated the association between attention-deficit/hyperactivity disorder (ADHD) and psychometrically defined cognitive variables across the adult life span, using data from a large controlled study of adults with and without ADHD. Comparisons were made between 2 groups of adults: participants with DSM-IV-diagnosed ADHD who had never received pharmacotherapy for their ADHD (n = 116) and 146 control participants. Subjects received a battery assessing IQ, neuropsychological measures, and academic testing. We modeled cognitive measures as a function of age and group status using linear regression. The study was conducted at Massachusetts General Hospital, Boston, between 1998 and 2003. ADHD and control subjects maintained similar, statistically significant differences in all psychometrically assessed measures of cognition within each decade that was represented (all P values < .01). The negative impact of ADHD on multiple, nonoverlapping, psychometrically assessed measures of cognition remained constant across the life cycle, suggesting that the association between ADHD and cognition neither improves nor deteriorates across the life cycle.