Caroly Pataki

Analog Classroom Assessment of a Once-Daily Mixed Amphetamine Formulation, SLI381 (ADDERALL XR), in Children With ADHD

OBJECTIVES This investigation was conducted primarily to assess the safety and efficacy of SLI381 (Adderall XR), developed as a once-daily treatment for children with attention-deficit/hyperactivity disorder (ADHD). Secondary objectives included examination of the time course, pharmacokinetic, and pharmacodynamic properties of SLI381. METHOD This was a randomized, double-blind, crossover study of three doses of SLI381 (10, 20, and 30 mg), placebo, and an active control (Adderall 10 mg) given once daily to 51 children with ADHD. Weekly assessments in an analog classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained every 1.5 hours over a 12-hour period. RESULTS SLI381 was well tolerated. All active treatment conditions displayed significant time course effects and were superior to placebo in improving efficacy measures. Dose-dependent improvements were evident for SLI381. SLI381 20 and 30 mg and Adderall all showed rapid improvements by 1.5 hours, but only the SLI381 20- and 30-mg doses showed continued activity at 10.5 and 12 hours for classroom behavior and math test performance versus placebo. CONCLUSIONS These data provide support for the benefit of this novel, once-daily amphetamine preparation in the treatment of ADHD. The longer duration of action of SLI381 has the potential to simplify psychostimulant dosing, thus reducing dose diversion and eliminating the need for in-school administration. SLI381 appears to be a useful treatment option for many children with ADHD.

The Effects of Methylphenidate and Lithium on Attention and Activity Level

Seven psychiatrically hospitalized prepubertal children were treated with methylphenidate, placebo, lithium carbonate alone and in combination with methylphenidate. Children met DSM-III-R criteria for both disruptive behavior disorder and bipolar or major depressive disorder by structured interview and consensus diagnosis. Parents, children, teachers, staff, and raters were blind to medication condition. Children were rated weekly on measures of attention and activity to determine whether medications alone or in combination produced a differential effect on these variables. The nosological and practical implications of the results are discussed.

Mood stabilizers in hospitalized children with bipolar disorder: A retrospective review

A paucity of naturalistic data supported a rationale for the present retrospective review of clinical changes during hospitalization in 44 bipolar pre‐adolescents, treated with monotherapy lithium, carbamazepine (CBZ) or divalproex sodium (DVP). Daily staff progress notes and discharge summaries on each patient were read by four trained clinicians blind to treatment group, and rated according to the Clinical Global Impression Improvement (CGI‐I) scale. Consensus rating was measured by kappa reliability. Data were analyzed using a general linear model (sas mixed) analysis of variance (anova) with repeated measures. The medication groups did not differ in length of hospitalization, overall severity of illness at the time of admission, or comorbidity. Prior treatment was considered as a covariate. Each group approached serum therapeutic levels at day 7 of the medication period. The estimated mean CGI‐I scores for CBZ were systematically higher (i.e. worse) than those for lithium and DVP, which overlapped and crossed over time. The difference became increasingly apparent and was statistically significant by week 2 (P = 0.036). The present study was limited in that the sample sizes, particularly in the case of CBZ, were small, commensurate with the low prevalence of the disorder. Lack of structured interviews, as an independent assessment of diagnoses was an intrinsic limitation of the study. Although constrained by its retrospective nature, our findings suggest that by week 2 of hospitalization both lithium and DVP may be more efficacious than CBZ in bipolar pre‐adolescents. Any significant finding must be viewed as tentative and subject to confirmation in other studies.

Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder

Medications for attention deficit hyperactivity disorder (ADHD) currently represent the ninth largest segment of the CNS market by sales, with US

New drugs for the treatment of attention-deficit/hyperactivity disorder

2.4 billion spent annually on this condition and 40% annual growth. Stimulant medications remain the most effective ADHD therapies and provide robust improvement in ADHD symptoms in both youth and adults. Current prescribing practices favor extended release preparations due to increased convenience, compliance and tolerability with once-daily dosing. Dexmethylphenidate extended release is a long-acting preparation of the ADHD medication Focalin® (dexmethylphenidate immediate release) and was approved for marketing by the US Food and Drug administration in June 2005. Dexmethylphenidate consists of the single dextro-isomer form of d,l-methylphenidate commonly marketed as Ritalin®. Dexmethylphenidate extended release utilizes spheroidal oral drug absorption system technology to achieve a 50% immediate medication delivery and 50% delayed release of dexmethylphenidate approximately 4 h after ingestion. Placebo-controlled, clinical trials in children and adults with ADHD have demonstrated efficacy for behavioral and academic ratings, with an analog classroom study showing medication effects up to 12 h after dosing. Dexmethylphenidate extended release was generally well tolerated with a side-effect profile similar to other stimulants. The most common reported side effects include diminished appetite and insomnia. Given its duration of effect, favorable tolerability and flexibility in dosing, dexmethylphenidate extended release is likely to gain considerable use as an ADHD treatment.

Complete remission of `treatment resistant' severe melancholia in adolescents with phenelzine: Two case reports

Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder of childhood. Recent research indicates that ADHD most often persists into adolescence and adulthood, and is associated with impairments in academic, social and occupational functioning. The ADHD diagnosis is based on history and clinical examination. There are no objective laboratory measures for diagnosis. ADHD is largely heritable. Its underlying pathophysiology has been theorised to include dysregulation of inhibitory noradrenergic frontocortical activity on dopaminergic striatal structures. Evidence shows that ADHD is highly responsive to pharmacological treatments resulting in global functional improvements. Although pharmacotherapy is recognised as the most effective treatment, additional components to optimise ADHD management include proper educational placement, parent management training and social skills development. Central nervous system stimulants, specifically methylphenidate and amphetamine, remain first-line pharmacological treatments. Atomoxetine, a selective noradrenergic re-uptake inhibitor, is the first non-stimulant compound to receive FDA approval for paediatric and adult ADHD. Other medication classes, including α-agonist antihypertensives, tricyclic antidepressants, other antidepressants such as buproprion, and the wake-promoting agent modafinil, are prescribed in off-label therapy. Ongoing development of new ADHD medications is expected to emphasise alternative and extended-release delivery systems and non-stimulant compounds.

Understanding Early Age of Onset: a Review of the Last 5 Years

We describe two cases of adolescents hospitalized with protracted courses of delusional melancholia who responded dramatically to treatment with phenelzine following multiple failed clinical trials with other agents and, in one case, ECT. The two cases are of interest in light of evidence linking delusional subtype of major depression in adolescents to bipolar disease, and the role of monoamine oxidase inhibitors in the management of adults with bipolar depression, as well as unipolar depressions unresponsive to other pharmacological treatments.

Second-generation antipsychotic medications in children and adolescents.

The age at onset of bipolar disorder ranging from childhood to adolescent to adult has significant implications for frequency, severity and duration of mood episodes, comorbid psychopathology, heritability, response to treatment, and opportunity for early intervention. There is increasing evidence that recognition of prodromal symptoms in at-risk populations and mood type at onset are important variables in understanding the course of this illness in youth. Very early childhood onset of symptoms including anxiety/depression, mood lability, and subthreshold manic symptoms, along with family history of a parent with early onset bipolar disorder, appears to predict the highest risk of early onset disorder with the most severe course.