Long-term effects of extended-release mixed amphetamine salts treatment of attention- deficit/hyperactivity disorder on growth

OBJECTIVE: The aim of this study was to examine the long-term effects of extended-release mixed amphetamine salts (MAS-XR) with 10-30-mg doses on the growth of children being treated for attention-deficit/hyperactivity disorder (ADHD). METHODS: Long-term growth data were collected from 568 children, 6-12 years of age, enrolled in a multicenter, open-label study of the safety of MAS-XR for the treatment of ADHD symptoms over the course of 6-30 months. RESULTS: Children taking MAS-XR grew less than expected, based on the norms provided by the Centers for Disease Control (CDC). The losses in expected weight and body mass index (BMI) were greatest for the heaviest children, and the losses in expected height were greatest for the tallest children. For weight, height, and BMI, we found that nearly all of the growth deficits occurred in year one. For each of these growth parameters, the loss in expected growth was not significant in the second year of treatment. CONCLUSIONS: Our results suggest that treatment with MAS-XR can lead to reductions in expected height and weight that are not fully rectified over the course of treatment, although they did show attenuation with treatment over time. Although this does not eliminate the need for clinicians to monitor growth, as they should for all stimulant formulations, it suggests that deficits in growth are not likely to be a clinical concern for most children treated with MAS-XR.     

Atomoxetine and stroop task performance in adult attention-deficit/hyperactivity disorder

OBJECTIVE: The aim of this study was to assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, for executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Two identical studies using a double-blind, placebo-controlled, parallel design were conducted. Patients were adults (Study 1, n = 280; Study 2, n = 256) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-defined ADHD recruited by referral and advertising. They were randomized to 10 weeks of treatment with atomoxetine or placebo. Executive functions were measured by the Stroop task. RESULTS: There was no evidence of cognitive deterioration associated with atomoxetine treatment. Atomoxetine treatment was associated with an improvement of the Stroop colorword score. CONCLUSIONS: Our results provide further support for Spencer et al.'s (1998) report that atomoxetine improves inhibitory capacity, as measured by the Stroop task. The absence of cognitive deterioration from atomoxetine, along with improved performance in a subgroup of patients in this large study, supports the safety of atomoxetine in this regard and its potential for improving a significant source of impairment for adults with ADHD.     

Impact of comorbidity in adults with attention-deficit/hyperactivity disorder

Persistence of attention-deficit/hyperactivity disorder (ADHD) into adulthood and male-to-female ratios of this disorder in childhood and adulthood have been controversial issues in the ADHD diagnosis in adults. Research has resolved these controversies and in turn provided support for the validity of the diagnosis in adults. Support for the diagnosis can also be found in data that show the lifetime prevalence rate for comorbid conditions such as antisocial disorders, mood and anxiety disorders, and substance abuse disorders to be consistent across pediatric and adult populations with ADHD. These coexisting conditions add not only to the impairment associated with ADHD in adults but also to the disorder's economic burden, the extent of which is currently unknown. However, adults with the disorder, like children, probably have higher health care use and costs than people without the disorder. Little, too, is known about the social cost of ADHD, but if left untreated, the impact may be substantial. Research to determine the occupational costs associated with ADHD is ongoing, but until that and other cost-of-illness data are available, studies on the economic costs of the comorbid conditions depression, anxiety, and substance abuse and dependence may be used to make suppositions about the economic impact of ADHD in adults. More studies are needed on the outcomes of adults with this disorder, especially cost-of-illness studies.     

Multiple-dose pharmacokinetics of fluvoxamine in children and adolescents

OBJECTIVE: To determine the pharmacokinetics of fluvoxamine in children and adolescents and to compare pharmacokinetic data from adolescents to adults from a previous study. METHOD: Fluvoxamine was titrated to a target dose of 100 mg b.i.d. in children (6-11 years) and 150 mg b.i.d. in adolescents (12-17 years) with obsessive-compulsive disorder or other disorder requiring fluvoxamine treatment. Serum samples were collected over 12 hours after 12 or more consecutive doses of 25, 50, 100, and 150 mg. RESULTS: Sixteen children (seven females, nine males) and 18 adolescents (nine females, nine males) were included in the pharmacokinetic analyses. Children demonstrated higher mean peak plasma concentration, higher mean area under the plasma concentration-time curve, and lower apparent oral clearance compared with adolescents. Compared with male children, female children had higher mean area under the plasma concentration-time curve, higher mean peak plasma concentration, and more reports of adverse events. However, the area under the plasma concentration-time curve was not directly correlated with frequency or severity of adverse events. Pharmacokinetics were nonlinear over the dose range studied. No pharmacokinetic differences were apparent between adolescents and adults on 150 mg b.i.d. CONCLUSIONS: These pharmacokinetic results suggest that children (especially females) have a higher exposure to fluvoxamine than adolescents, whereas adolescents and adults appear to have similar exposure to fluvoxamine.     

No seizure exacerbation from risperidone in youth with comorbid epilepsy and psychiatric disorders: a case series

OBJECTIVE: The aim of this study was to study risperidone use in pediatric patients with comorbid epilepsy and psychiatric disorders. METHOD: We retrospectively reviewed the outpatient psychopharmacology medical records of patients with epilepsy, aged 19 and younger, who received risperidone for psychiatric disorders. RESULTS: Twenty-one (21) youths (mean age, 12.0 +/- 4.2 years) met our criteria for review. Mean risperidone dosage was 2.4 +/- 3.5 mg/day. Target symptoms included severe aggression, severe agitation, psychosis, and self-injurious behavior. Diagnoses included attention-deficit hyperactivity disorder (ADHD), learning disorder, and impulse control disorder. Seizure type was partial complex in 12 patients, generalized in 6 patients, neonatal in 1 patient, myoclonic in 1 patient, and unclassified in 1 patient. The average number of previous psychotropic trials was 3.5 +/- 3.0. Using a definition of response of a Clinical Global Impressions (CGI) improvement score of 2 or less, 15 patients (71%) were considered responders. Adverse effects were none to slight in 16 patients, moderate in 4 patients, and severe in 1 patient. Seizures did not worsen in any patient. CONCLUSIONS: Risperidone was associated with a clinically significant global improvement, without seizure exacerbation in youths with epilepsy and psychiatric disorders. Despite the limitations of the study design, the 71% responder rate is noteworthy in this treatment-refractory group.     

Current concepts in the validity,diagnosis and treatment of paediatric bipolar disorder

Despite ongoing controversy, the view that paediatric bipolar disorder is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. This research strongly suggests that paediatric bipolar disorder may not be rare but that it may be difficult to diagnose. Since children with bipolar disorder are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset bipolar disorder may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. As recommended by Robins and Guze [American Journal of Psychiatry (1970), 126, 983-987], a psychiatric disorder may be considered a valid diagnostic entity if it can be shown to have differentiating features, evidence of familiality, specific treatment responsivity and a unique course. The goal of this article is to review our work and the extant literature within this framework to describe the evidence supporting bipolar disorder in children as a valid clinical diagnosis.     

Defining a developmental subtype of bipolar disorder in a sample of nonreferred adults by age at onset

OBJECTIVE: To test the hypothesis that the age at onset of bipolar disorder would identify a developmental subtype of bipolar disorder in adults characterized by increased levels of irritability, chronic course, rapid cycling, and comorbidity with attention deficit hyperactivity disorder. METHODS: Forty-four adult subjects diagnosed with bipolar disorder were selected from large family studies of youth with and without attention deficit hyperactivity disorder. These subjects were stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%), adolescence (13-18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24, 55%). All subjects were administered structure diagnostic interviews and a brief cognitive battery. RESULTS: In contrast with adult-onset bipolar disorder, child-onset bipolar disorder was associated with a longer duration of illness, more irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling course, and increased comorbidity with childhood disruptive behavior disorders and anxiety disorders. CONCLUSION: Stratification by age at onset of bipolar disorder identified subgroups of adult subjects with differing clinical correlates. This pattern of correlates is consistent with findings documented in children with pediatric bipolar disorder and supports the hypothesis that child-onset bipolar disorder may represent a developmental subtype of the disorder.     

Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a reanalysis using drug-placebo and drug-drug response curve methodology.

Because methylphenidate (MPH) is currently the most widely prescribed medication for attention deficit hyperactivity disorder (ADHD), several studies have used this as the touch-stone for evaluating the efficacy of a newer stimulant, Adderall. In a parallel-groups study of MPH (n = 20), Adderall (n = 20), and placebo (n = 18), Pliszka et al. (2000) reported that both medications were superior to placebo in improving parent, teacher, and clinician ratings of ADHD and associated behaviors. Compared with MPH, Adderall led to significantly more improvements in teacher and clinician ratings. The present study extends these results by addressing the issue of clinical significance using drug-placebo and drug-drug response curve analyses of the same data. The goal of this method is to answer the following questions about drug-placebo or drug-drug differences: Is the effect clinically meaningful? What does the effect tell us about individual responses? Is the effect due to symptom improvement, the prevention of worsening, or both? Our results show that the efficacy of Adderall to improve functioning is seen throughout the full range of improvement scores. In contrast, MPH showed a substantial effect for "mildly" and "much improved" but not for "very much improved." Our analyses also show that both Adderall and MPH prevent worsening of symptoms. They further suggest that, compared with the Conners Teacher Rating Scale, the Clinical Global Impressions scale may be more sensitive to improvements at the "well end" of the spectrum of functioning.