Impact of race on efficacy and safety during treatment with olanzapine in schizophrenia, schizophreniform or schizoaffective disorder

<p>Abstract</p> <p>Background</p> <p>To examine potential differences in efficacy and safety of treatment with olanzapine in patients with schizophrenia of white and black descent.</p> <p>Methods</p> <p>A post-hoc, pooled analysis of 6 randomized, double-blind trials in the treatment of schizophrenia, schizophreniform disorder, or schizoaffective disorder compared white (N = 605) and black (N = 375) patients treated with olanzapine (5 to 20 mg/day) for 24 to 28 weeks. Efficacy measurements included the Positive and Negative Syndrome Scale (PANSS) total score; and positive, negative, and general psychopathology scores; and the Clinical Global Impression of Severity (CGI-S) scores at 6 months. Safety measures included differences in the frequencies of adverse events along with measures of extrapyramidal symptoms, weight, glucose, and lipid changes over time.</p> <p>Results</p> <p>51% of black patients and 45% of white patients experienced early study discontinuation (P = .133). Of those who discontinued, significantly more white patients experienced psychiatric worsening (P = .002) while significantly more black patients discontinued for reasons other than efficacy or tolerability (P = .014). Discontinuation for intolerability was not different between groups (P = .320). For the estimated change in PANSS total score over 6 months, there was no significant difference in efficacy between white and black patients (P = .928), nor on the estimated PANSS positive (P = .435), negative (P = .756) or general psychopathology (P = .165) scores. Overall, there was no significant difference in the change in CGI-S score between groups from baseline to endpoint (P = .979). Weight change was not significantly different in white and black patients over 6 months (P = .127). However, mean weight change was significantly greater in black versus white patients at Weeks 12 and 20 only (P = .028 and P = .026, respectively). Additionally, a significantly greater percentage of black patients experienced clinically significant weight gain (≥7%) at anytime compared to white patients (36.1% vs. 30.4%, P = .021). Changes across metabolic parameters (combined fasting and random lipids and glucose) were also not significantly different between groups, with the exception of a greater categorical change in total cholesterol from borderline to high among white subjects and a categorical change from normal to low in high density lipoprotein (HDL) cholesterol among white males.</p> <p>Conclusions</p> <p>The findings did not demonstrate overall substantive differences in efficacy or safety between white and black patients diagnosed with schizophrenia or related disorders treated with olanzapine. However, a significantly greater percentage of black patients (36.1%) experienced clinically significant weight gain compared to white patients (30.4%).</p

Prevalence of nonmedical methamphetamine use in the United States

<p>Abstract</p> <p>Background</p> <p>Illicit methamphetamine use continues to be a public health concern in the United States. The goal of the current study was to use a relatively inexpensive methodology to examine the prevalence and demographic correlates of nonmedical methamphetamine use in the United States.</p> <p>Methods</p> <p>The sample was obtained through an internet survey of noninstitutionalized adults (n = 4,297) aged 18 to 49 in the United States in 2005. Propensity weighting methods using information from the U.S. Census and the 2003 National Survey on Drug Use and Health (NSDUH) were used to estimate national-level prevalence rates.</p> <p>Results</p> <p>The overall prevalence of current nonmedical methamphetamine use was estimated to be 0.27%. Lifetime use was estimated to be 8.6%. Current use rates for men (0.32%) and women (0.23%) did not differ, although men had a higher 3-year prevalence rate (3.1%) than women (1.1%). Within the age subgroup with the highest overall methamphetamine use (18 to 25 year olds), non-students had substantially higher methamphetamine use (0.85% current; 2.4% past year) than students (0.23% current; 0.79% past year). Methamphetamine use was not constrained to those with publicly funded health care insurance.</p> <p>Conclusion</p> <p>Through the use of an internet panel weighted to reflect U.S. population norms, the estimated lifetime prevalence of methamphetamine use among 18 to 49 year olds was 8.6%. These findings give rates of use comparable to those reported in the 2005 NSDUH. Internet surveys are a relatively inexpensive way to provide complimentary data to telephone or in-person interviews.</p

Atomoxetine Effects on Executive Function as Measured by the BRIEF-A in Young Adults with ADHD: A Randomized, Double-Blind, Placebo-Controlled Study

<div><p>Objective</p><p>To evaluate the effect of atomoxetine treatment on executive functions in young adults with attention-deficit/hyperactivity disorder (ADHD).</p><p>Methods</p><p>In this Phase 4, multi-center, double-blind, placebo-controlled trial, young adults (18–30 years) with ADHD were randomized to receive atomoxetine (20–50 mg BID, N = 220) or placebo (N = 225) for 12 weeks. The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) consists of 75 self-report items within 9 nonoverlapping clinical scales measuring various aspects of executive functioning. Mean changes from baseline to 12-week endpoint on the BRIEF-A were analyzed using an ANCOVA model (terms: baseline score, treatment, and investigator).</p><p>Results</p><p>At baseline, there were no significant treatment group differences in the percentage of patients with BRIEF-A composite or index T-scores ≥60 (<i>p></i>.5), with over 92% of patients having composite scores ≥60 (≥60 deemed clinically meaningful for these analyses). At endpoint, statistically significantly greater mean reductions were seen in the atomoxetine versus placebo group for the BRIEF-A Global Executive Composite (GEC), Behavioral Regulation Index (BRI), and Metacognitive Index (MI) scores, as well as the Inhibit, Self-Monitor, Working Memory, Plan/Organize and Task Monitor subscale scores (<i>p</i><.05), with decreases in scores signifying improvements in executive functioning. Changes in the BRIEF-A Initiate (<i>p</i> = .051), Organization of Materials (<i>p</i> = .051), Shift (<i>p</i> = .090), and Emotional Control (<i>p</i> = .219) subscale scores were not statistically significant. In addition, the validity scales: Inconsistency (<i>p</i> = .644), Infrequency (<i>p</i> = .097), and Negativity (<i>p</i> = .456) were not statistically significant, showing scale validity.</p><p>Conclusion</p><p>Statistically significantly greater improvement in executive function was observed in young adults with ADHD in the atomoxetine versus placebo group as measured by changes in the BRIEF-A scales.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/show/NCT00510276" target="_blank">NCT00510276 </a></p></div

Participant disposition flow diagram.

<p>Participant disposition flow diagram.</p

BRIEF-A Mean Change from Baseline to Last Observation for All Randomized Patients.

a<p>n includes all randomized patients who also had a baseline score and at least one post-baseline score on the BRIEF-A scale.</p>b<p>All <i>p</i>-values were statistically significant (<i>p</i>≤.05) except for Shift, Emotional Control, Initiative, and Organization of Materials; 9 component score p-values adjusted with Hochberg’s Method to control for potential multiplicity.</p><p>Abbreviations: n = number of participants; SD = standard deviation.</p

Patient Baseline Characteristics.

a<p>N includes all randomized patients.</p>b<p>Analysis of variance (ANOVA) model: baseline = treatment (Type III sums of squares).</p>c<p>Treatment comparison was analyzed using Fisher’s exact test.</p><p>Abbreviations: ADHD = attention-deficit/hyperactivity disorder; DSM-IV-TR = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision; N = total number of participants; n = number of participants in the specified category; SD = standard deviation.</p

BRIEF-A Mean Change from Baseline to Postbaseline Visits for All Randomized Patients – Repeated Measures Analysis for Global Executive Composite Scores.

a<p>n includes all randomized patients who also had a BRIEF-A baseline score and a postbaseline score at Visit 4 (Week 5) and/or Visit 6 (Week 12), as applicable.</p><p>Abbreviations: CI = confidence interval; LS = least squares; n = number of participants; SE = standard error.</p

Neurophysiologic predictors of response to atomoxetine in young adults with attention deficit hyperactivity disorder: a pilot project.

Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a useful pharmacologic treatment option for young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). It is difficult to determine, however, those patients for whom atomoxetine will be both effective and advantageous. Patients may need to take the medication for several weeks before therapeutic benefit is apparent, so a biomarker that could predict atomoxetine effectiveness early in the course of treatment could be clinically useful. There has been increased interest in the study of thalamocortical oscillatory activity using quantitative electroencephalography (qEEG) as a biomarker in ADHD. In this study, we investigated qEEG absolute power, relative power, and cordance, which have been shown to predict response to reuptake inhibitor antidepressants in Major Depressive Disorder (MDD), as potential predictors of response to atomoxetine. Forty-four young adults with ADHD (ages 18-30) enrolled in a multi-site, double-blind placebo-controlled study of the effectiveness of atomoxetine and underwent serial qEEG recordings at pretreatment baseline and one week after the start of medication. qEEG measures were calculated from a subset of the sample (N&nbsp;=&nbsp;29) that provided useable qEEG recordings. Left temporoparietal cordance in the theta frequency band after one week of treatment was associated with ADHD symptom improvement and quality of life measured at 12 weeks in atomoxetine-treated subjects, but not in those treated with placebo. Neither absolute nor relative power measures selectively predicted improvement in medication-treated subjects. Measuring theta cordance after one week of treatment could be useful in predicting atomoxetine treatment response in adult ADHD