A systematic review of the safety of lisdexamfetamine dimesylate

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals

An Organic-solid With Wide Channels Based On Hydrogen-bonding Between Macrocycles

RESEARCH on microporous solids has focused largely on inorganic materials such as aluminosilicates (zeolites), aluminophosphates, pillared clays and other layered materials(1,2). An elusive goal has been the design of new materials with specific properties such as selective adsorption and catalytic activity. It would be very useful if the tools of molecular synthesis could be brought to bear on this problem. Here we report the design, based on a modular approach, and the crystal structure of an organic solid with large-diameter (about 9 Angstrom) extended channels. The channels are formed from planar, rigid macrocyclic building blocks. Onto the outer rim of the macrocycles are attached phenolic groups, which form hexagonally closest-packed two-dimensional hydrogen-bonded networks. Extended channels result from the stacking of these layers in a way that maintains registry between the macrocyclic cavities, and these channels are filled with solvent molecules. This approach potentially offers a simple means to exercise control over pore size and shape in the solid state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62826/1/371591a0.pd

Thicker Temporal Cortex Associates with a Developmental Trajectory for Psychopathic Traits in Adolescents

Psychopathy is a clinical condition characterized by a failure in normal social interaction and morality. Recent studies have begun to reveal brain structural abnormalities associated with psychopathic tendencies in children. However, little is known about whether variations in brain morphology are linked to the developmental trajectory of psychopathic traits over time. In this study, structural magnetic resonance imaging (sMRI) data from 108 14-year-old adolescents with no history of substance abuse (54 males and 54 females) were examined to detect cortical thickness variations associated with psychopathic traits and individual rates of change in psychopathic traits from ages 9 to 18. We found cortical thickness abnormalities to correlate with psychopathic traits both cross-sectionally and longitudinally. Specifically, at age 14, higher psychopathic scores were correlated with thinner cortex in the middle frontal gyrus, particularly in females, and thicker cortex in the superior temporal gyrus, middle temporal gyrus, and parahippocampal gyrus, particularly in males. Longitudinally, individual rates of change in psychopathic tendency over time were correlated with thicker cortex in the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, parahippocampal gyrus, and posterior cingulate gyrus, particularly in males. Findings suggest that abnormal cortical thickness may reflect a delay in brain maturation, resulting in disturbances in frontal and temporal functioning such as impulsivity, sensation-seeking, and emotional dysregulation in adolescents. Thus, findings provide initial evidence supporting that abnormal cortical thickness may serve as a biomarker for the development of psychopathic propensity in adolescents

Measuring oral sensitivity in clinical practice: A quick and reliable behavioural method.

This article aims to offer a behavioural assessment strategy for oral sensitivity that can be readily applied in the clinical setting. Four children, ranging in age and with a variety of developmental and medical problems, were used as test cases for a task analysis of tolerance to touch probes in and around the mouth. In all cases, the assessment was sensitive to weekly measures of an intervention for oral sensitivity over a 3-week period. Employing an inexpensive, direct, specific to the individual, replicable, reliable, and effective measure for a specific sensory problem would fit better with the edicts of evidence-based practice. The current method offered the initial evidence towards this goal