Objectives: Possible disease-modifying effects of rivastigmine have been suggested by analyses using a variation of the randomized start design; however, the results were somewhat confounded by differing attrition rates. We report on an alternative method investigating whether increasing doses reduce the rates of cognitive decline in patients who continue treatment.

Methods: The effect of dose on the rate of cognitive decline seen on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was explored for patients in a long-term (130-week) extension of a 26-week placebo-controlled trial using two methods: a weighted leas squares regression analysis using each individual's slope, and a weighted analysis of variance (ANOVA) comparing the slopes of patients categorized by dose (≤6 mg/d or >6 mg/d).

Results: The results from 408 patients included in the weighted least squares analysis estimated the rate of decline to attenuate by approximately 1 point/y for every 3 mg/d increase (P<.0001). The average annual rate of decline for patients whose mean dose was >6 mg/d was 4.5 points (95% Cl, 5.1–3.9), while for patients with a mean dose of≥6 mg/d a decline of 8.2 points (95% Cl, 9.1–7.3) was seen.

Conclusion: These data further support earlier results suggesting that rivastigmine reduces the rate of progression of cognitive deterioration in Alzheimer's disease.

Objective: Nearly 50% of patients with schizophrenia hav ecomorbid anxiety disorders. Ziprasidone's unique pharmacological profile, including 5-HT1A agaonism and 5-HT and NE reuptake inhibition, may confer anxiolytic properties. And exploratory analysis was conducted to evaluate improvement in anxiety in stable schizophrenic outpatients, as standard scales assessing psychosis do not adequately address anxity. Stable outpatients were selected to reduce the influence of acute psychosis.

Methods: Patients on conventional antipsychotics (n=93), olanzapine (n=88), and risperidone (n=41) were randomized to one of three dosing schedules and received ziprasidone 40–160 mg/day in three 6-week, open-label trials. Anxiety was measured by the PANSS anxiety item (G2: 1, absent, to 7, extreme). Analysis of patients with moderate or greater anxiety (≥4), as well as analysis of those with at least minimal anxiety (≥2), was conducted. Other symptom items were analyzed to address the speccificity of potential treatment differences.

Results: In patients with moderate or greater baseline anxiety, significant improvement in the PANSS anxiety time was observed (P<0.05). Significant improvement was also seen in the group of patients with at least minimal baseline anxiety (P<0.05). There were no concomitant signigicant changes in depression or somatic concern in the moderate anxiety subsample.

Conclusions: Improvement in the PANSS anxiety item, separate from changes in depression and somatic concern, was observed. In view of the prevalence of anxiety symptoms in schizophrenia, controlled trials utilizing anxiety scales validated in this population are necessary to further evaluate ziprasidone's anxwlytk potential.

Although the concept of pharmacotherapyfor attention-deficit/hyperactivity disorder (ADHD) was first introduced more than 60 years ago, treatment of this disorder remains more controversial than ever. It is hoped, however, that the recent Consensus Development Conference (CDC) Statement on the diagnosis and treatment of ADHD will not only help answer some of the questions surrounding management of this disorder, but also lend needed scientific weight to debate in this area. While more research in ADHD is needed, the CDC partic ipants pointed to a solid body of evidence showing that careful medication management can result in noticeable improvement in several measures, with little risk of adverse events.

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder characterized by inattention, impulsivity, and overactivity that begins in childhood. While considerable research has focused on the neurobiological substrates of this disorder, the specific nature of the brain dysfunction in ADHD has remained elusive. However, early data from pharmacological treatment studies, as well as from basic research in animals and humans, initially led several investigators to develop neurobiological models of ADHD. These models of ADHD and more recent evidence from neuropsychological, neuroimaging, neurochemical, and genetic research are briefly reviewed. While not completely consistent, the empirical data suggest that dysfunction in prefrontal-striatal neural circuits, as well as in brain stem catecholamine systems that innervate these circuits, may underlie the executive function deficits in ADHD.

The predominantly inattentive (IN) subtype of attention-deficit/hyperactivity disorder (ADHD) is a recently defined condition that is often overlooked by professionals and is still not completely understood. Characterized by symptoms of inattentiveness, such as distractibility, failure to complete work, forgetfulness, and disorganization, the IN subtype differs from the more commonly recognized combined (CB) subtype of ADHD in that symptoms of hyper activity and impulsivity are absent or minimal. Large-scale epidemiologic studies suggest that the IN subtype is at least as prevalent as the CB subtype, and is at least as likely to be associated with academic and/or social impairment. Diagnosis of the IN subtype, however, may be more challenging because in addition to inattentiveness, other symptoms, including learning problems, depression, and anxiety, may also present without externalizing behaviors. Several studies have shown that compared with the CB subtype, the IN subtype has a later age of onset and referral, a relatively larger proportion of affected females, and is much less likely to be associated with symptoms of oppositional defiant disorder or conduct disorder. Research is currently under way to examine the cognitive characteristics of the IN subtype and its genetic and neurobiologic underpinnings, as well as to evaluate the effectiveness of pharmacotherapy and other treatments.

The present investigation examined factors that predict physical aggression in children with attention-deficit/hyperactivity disorder (ADHD). Stepwise, multiple regression-analyses were used to examine predictors of children's physical aggression as rated by parents at a 1-year follow-up point and by teachers at both 1- and 2-year follow-up points. Early parent and teacher ratings of verbal aggression (ie, cursing, teasing, and threatening) accounted for the greatest proportion of the variance in physical aggression ratings obtained at follow-up. None of the other predictor variable, including early ratings of physical aggression and ADHD behaviors, contributed significant additional variance beyond that accounted for by early verbal aggression ratings. Temporal and cross-informant analyses revealed that the relationship between verbal aggression and later physical aggression was situation-specific for teacher ratings but no parent ratings. Although physical aggression may emerge early in development, these data suggest that verbal aggre sion represents a stable, temperamental characteristic that may be of greater value than early physical aggression for predicting later physically aggressive acts.

The performance of nine adults with attention-deficit/hyperactivity disorder (ADHD) was compared with the performance of 23 normal controls on computerized measures of target orientation, sustained attention, encoding speed, and motor output/response organization to determine the nature of the neurocognitive deficits of adults with ADHD. While the groups' performances on measures of sustained attention and encoding speed did not differ, significant group differences were seen on a task that targeted motor output/response organization. These data suggest that the neurocognitive difficulties of ADHD adults are not related to a primary deficit in sustained attentional functioning. Rather, the deficient information processing in ADHD adults is related to difficulties with motor output/response organization.