Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

Ann E Maloney1,2, Linmarie Sikich31Maine Medical Center Research Institute, Scarborough, ME, USA; 2Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA; 3Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USABackground: Severe and persistent mental illnesses in children and adolescents, such as early-onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.Methods: PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.Results: Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.Conclusions: The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth.Keywords: early-onset schizophrenia, pediatric bipolar disorder, antipsychoti

Early Pharmacological Treatment of Autism: A Rationale for Developmental Treatment

Autism is a dynamic neurodevelopmental syndrome in which disabilities emerge during the first three postnatal years and continue to evolve with ongoing development. We briefly review research in autism describing subtle changes in molecules important in brain development and neurotransmission, in morphology of specific neurons, brain connections and in brain size. We then provide a general schema of how these processes may interact with particular emphasis on neurotransmission. In this context, we present a rationale for utilizing pharmacologic treatments aimed at modifying key neurodevelopmental processes in young children with autism. Early treatment with selective serotonin reuptake inhibitors (SSRIs) is presented as a model for pharmacologic interventions because there is evidence in autistic children for reduced brain serotonin synthesis during periods of peak synaptogenesis; serotonin is known to enhance synapse refinement; and exploratory studies with these agents in autistic children exist. Additional hypothetical developmental interventions and relevant published clinical data are described. Finally, we discuss the importance of exploring early pharmacologic interventions within multiple experimental settings in order to develop effective treatments as quickly as possible while minimizing risks

Pilot Study of an Active Screen Time Game Correlates with Improved Physical Fitness in Minority Elementary School Youth

The aim of our feasibility study was to examine the acceptability and utility of “Dance Dance Revolution” (DDR) (Konami of America, Redwood City, CA)) to increase physical fitness in 8–11-year-old black and Hispanic youth

Mapping social target detection with functional magnetic resonance imaging

The neural correlates of cognitive control and social processing functions, as well as the characteristic patterns of anomalous brain activation patterns in psychiatric conditions associated with impairment in these functions, have been well characterized. However, these domains have primarily been examined in isolation. The present study used event-related functional magnetic resonance imaging to map brain areas recruited during a target-detection task designed to evaluate responses to both non-social (i.e. shape) and social (i.e. face) target stimuli. Both shape and face targets activated a similar brain network, including the postcentral gyrus, the anterior and posterior cingulate gyri and the right midfrontal gyrus, whereas face targets additionally activated the thalamus, fusiform and temporooccipital cortex, lingual gyrus and paracingulate gyrus. Comparison of activations to social and non-social target events revealed that a small portion of the dorsal anterior cingulate gyrus (Brodmann's area 32) and the supracalcarine cortex were preferentially activated to face targets. These findings indicate that non-social and social stimuli embedded within a cognitive control task activate overlapping and distinct brain regions. Clinical cognitive neuroscience research of disorders characterized by cognitive dysfunction and impaired social processing would benefit from the use of tasks that evaluate the combined effects of deficits in these two domains

A Pilot Study of Neuroplasticity Based Cognitive Remediation in Early Onset Psychosis

Introduction – Neuroplasticity based auditory and visual training programs appear to improve neurocognitive function in adults with schizophrenia, but use in younger individuals has not been determined. We hypothesized that adolescents might play more often and respond better than adults to training using a game-like laptop in their home environment. Methods -- Youth 10-19 years with Early Onset Psychosis (EOP) were provided a laptop and randomly assigned to play games to enhance basic auditory, visual and social processing neuroplasticity games (NPG) or assigned to control games with cognitive components, such as Sudoku or hangman or (CG). All received neurocognitive assessments at baseline, intervention completion and 4 months post treatment. Results — 12 youth (15.5 +3.2 yrs) were assigned to NPG and 10 participants (16.2 +2.1 years) were assigned to CG. More NPG than CG participants completed the prescribed hours of game play (block 1 - 92% vs. 70% over the first 40 hours), with both groups engaged less over time. Although most neurocognitive functions did not change, the NPG group did show improvements in WRAML Visual Learning, WISC Digit Span Forward, Spatial Span Backwards and CPT omission errors. Surprisingly, satisfaction was lower for NPG than CG. Conclusions — Groups were well matched for baseline illness characteristics. On the global measures of cognition, both EOP groups showed improvement over time but those improvements were generally greater in the CG than in the NPG group, with potentially significant differences favoring the CG evident in the neurocognitive composite score (p=0.072) and BRIEF metacognition (p=.117). Youth did not play as frequently or as long as requested despite providing a laptop for their home use and stipends for playing

fMRI tracks reductions in repetitive behaviors in autism: Two case studies

Autism is characterized by abnormal prefrontal brain activation during cognitive control, a potential biomarker of repetitive behaviors. In this proof-of-principle study, functional magnetic resonance imaging (fMRI) was used to examine brain activity during an oddball task in two high-functioning males with autism before and after 12 weeks of treatment with citalopram, a selective serotonin reuptake inhibitor. One participant showed marked reductions in repetitive behaviors whereas the other showed mild worsening. Brain activation in relevant prefrontal regions increased in only the participant whose repetitive behavior symptoms improved. These findings suggest that fMRI may elucidate potential mechanisms of action of targeted autism interventions

STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ≥17 on the Aberrant Behavior Checklist (ABC)—Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted.Seaside Therapeutics Inc

Post-Acute Effectiveness of Lithium in Pediatric Bipolar I Disorder

This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions

Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders: A Multisite Randomized Clinical Trial

The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population