Effects of lisdexamfetamine in a rat model of binge-eating.

Binge-eating disorder is a common psychiatric disorder affecting ~2% of adults. Binge-eating was initiated in freely-fed, lean, adult, female rats by giving unpredictable, intermittent access to ground, milk chocolate over four weeks. The rats avidly consumed chocolate during 2 hr binge sessions, with compensatory reductions of normal chow intake in these sessions and the days thereafter.

Differences in the neurochemical and behavioural profiles of lisdexamfetamine methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis and locomotor activity measurements in freely-moving rats.

Lisdexamfetamine dimesylate is a novel prodrug approved in North America, Europe and Brazil for treating attention deficit hyperactivity disorder (ADHD). It undergoes rate-limited hydrolysis by red blood cells to yield d-amphetamine. Following our previous work comparing lisdexamfetamine with d-amphetamine, the neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement.

A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil.

Lisdexamfetamine dimesylate, which consists of L-lysine covalently bound to D-amfetamine, is the first prodrug for treating ADHD. Its metabolic conversion to yield D-amfetamine by rate-limited, enzymatic hydrolysis is unusual because it is performed by peptidases associated with red blood cells. Other stimulants shown to be effective in managing ADHD include D-amfetamine, methylphenidate and modafinil.

Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study).

Objectives: This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses.

Background: The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis.

Adult congenital heart disease interventions: recommendations from a joint working group of the British Congenital Cardiac Association, British Cardiovascular Intervention Society, and the British Cardiovascular Society.

In order to optimise care of the adult patients with complex congenital heart disease, there is a need to develop recommendations for interventions. This document is the work of representatives of the three relevant societies and provides recommendations for institutions and operators performing cardiac interventions in these patients.

Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study.

Objectives: The purpose of this study was to develop an adenosine-independent, pressure-derived index of coronary stenosis severity.

Background: Assessment of stenosis severity with fractional flow reserve (FFR) requires that coronary resistance is stable and minimized. This is usually achieved by administration of pharmacological agents such as adenosine.

Estimation of symptom-free days in generalized anxiety disorder.

Objective: The efficacy of treatments for generalized anxiety disorder has usually been measured in terms of response or remission of symptoms. These endpoints, however, may not adequately capture the transient periods of symptom abatement and relapse characteristic of chronic psychiatric disorders. Here, we evaluate the measurement of treatment effectiveness in terms of the number of symptom-free days (SFDs).

Impact of gastrointestinal symptom severity on response to venlafaxine extended-release in patients with generalized anxiety disorder.

Background: This retrospective analysis evaluated the prevalence and severity of pre-treatment gastrointestinal (GI) symptoms in patients with generalized anxiety disorder (GAD), the impact of these GI symptoms on the efficacy and tolerability of venlafaxine extended-release (XR), and the effect of treatment on prestudy GI symptoms.

Method: Data from 1932 nondepressed GAD patients were pooled from 5 randomized, double-blind, placebo-controlled studies of venlafaxine XR clinically conducted between May 1995 and December 1997. The GI symptom severity at baseline was estimated from item 11 on the Hamilton Rating Scale for Anxiety (HAM-A).

Social adjustment in generalised anxiety disorder: a long-term placebo-controlled study of venlafaxine extended release.

The objective of this analysis was to evaluate the short- (8 weeks) and long-term (24 weeks) efficacy of three fixed doses of venlafaxine extended release (ER) and placebo on the social adjustment of patients with generalised anxiety disorder (GAD). We analysed data from 544 outpatients who participated in a 24-week, double-blind, multicentre, parallel-group, placebo-controlled study conducted at 55 centres in five countries. All patients meet the DSM-IV criteria for GAD and were randomly assigned to receive venlafaxine ER 37.

Venlafaxine versus placebo in the preventive treatment of recurrent major depression.

Background: Major depression is often chronic and recurrent, yet most long-term therapeutic trials are not adequately designed to assess antidepressant efficacy in recurrence prevention. Long-term efficacy and safety of prophylactic venlafaxine treatment were evaluated in outpatients with recurrent major depression.

Method: Patients with a history of recurrent DSM-III-R major depression received open-label treatment with venlafaxine, 100 to 200 mg/day, for 6 months.

Pooled analysis of venlafaxine XR efficacy on somatic and psychic symptoms of anxiety in patients with generalized anxiety disorder.

We evaluated the relative efficacy of venlafaxine XR on the psychic versus somatic symptoms of anxiety in patients with generalized anxiety disorder as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Data were pooled and analyzed from 1,841 patients with generalized anxiety disorder who participated in five short-term (8-week) double-blind, multicenter, placebo-controlled studies, two of which had long-term (6-month) extensions. Somatic and psychic anxieties were studied using the Hamilton rating scale for anxiety (HAM-A) factor scores.

Predictors of outcome following venlafaxine extended-release treatment of DSM-IV generalized anxiety disorder: a pooled analysis of short- and long-term studies.

This pooled analysis evaluated potential predictive abilities of baseline demographic factors, psychiatric history, and DSM-IV diagnostic criteria for short- and long-term outcome after treatment with venlafaxine extended release (XR) or placebo in patients with generalized anxiety disorder (GAD). Pooled data from 1,839 patients in five placebo-controlled studies of venlafaxine XR for GAD were analyzed by logistic regression. Odds ratios (ORs) were used to quantify pretreatment factors' abilities to predict response (50% reduction, baseline Hamilton Rating Scale for Anxiety [HAM-A] severity) and remission (total HAM-A score View Article and Find Full Text PDF

A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder.

This randomised, double-blind, placebo-controlled study compared the efficacy of venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment period in 540 non-depressed outpatients with generalised anxiety disorder (GAD). At week 8, significant improvements from baseline were observed in the venlafaxine XR, diazepam and placebo groups. Although these improvements were higher in the first two groups than in the placebo group for each of the primary efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub-scale and Clinical Global Impression (CGI) improvement), there were no statistically significant differences between groups.

Effectiveness of venlafaxine, extended release formulation, in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis.

A survival analysis of data from two placebo-controlled, randomized, long-term (6-month) studies was used to examine the effectiveness of venlafaxine, extended release (XR) formulation, in patients with generalized anxiety disorder (GAD). Patients in a placebo-controlled, flexible-dose study received 75 to 225 mg/day venlafaxine XR, while patients in a placebo-controlled, fixed-dose study received once-daily venlafaxine XR doses of 37.5 mg, 75 mg, or 150 mg.

Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms.

Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces significantly higher remission rates in depressed patients than do the selective serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we explored the relationship between differences in treatment efficacy, early improvement of symptoms, and severity of baseline anxiety in depressed patients treated with either venlafaxine or fluoxetine. A pooled analysis was performed on data from 1,454 outpatients with major depression from five double-blind, randomized studies comparing the 6-week efficacy of venlafaxine (542 patients) with fluoxetine (555 patients).

Characterization of the longitudinal course of improvement in generalized anxiety disorder during long-term treatment with venlafaxine XR.

Objective: To characterize the response to the serotonin and norepinephrine reuptake inhibitor, venlafaxine extended release (XR), during the long-term treatment of generalized anxiety disorder.

Methods: Data from two double-blind, placebo-controlled, 6-month trials of venlafaxine XR for the treatment of generalised anxiety disorder were pooled. Criteria for response (> or = 50% improvement from baseline HAM-A score) and remission (HAM-A score < or = 7) and their temporal profile were used to characterize patient improvement over 6 months of treatment with venlafaxine XR and placebo.

Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials.

Objectives: Concerns about the safety of benzodiazepines in older adults may have led investigators and clinicians to underestimate the importance of adequately treating generalized anxiety disorder (GAD) in later life. To evaluate the safety and efficacy profile of an alternative treatment in older patients, we conducted a secondary analysis of five randomized, placebo-controlled clinical trials of extended release venlafaxine (venlafaxine ER, Effexor XR) for adult patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of GAD.

Design: The five multicenter, parallel-group, double-blind, prospectively randomized, placebo-controlled clinical trials used similar designs to evaluate short-term efficacy after 8 weeks.