An open-label study of naltrexone and bupropion combination therapy for smoking cessation in overweight and obese subjects.

A combination of sustained release (SR) naltrexone (32 mg/day) and bupropion SR (360 mg/day) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain. Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week, open-label study; 85% and 63% completed 12 and 2 4weeks, respectively. The target quit date was Week 4.

Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo.

Context: The efficacy of current centrally acting obesity pharmacotherapies is limited by compensatory mechanisms that mitigate weight loss.

Objective: Our objective was to determine whether opioid receptor antagonism (naltrexone) plus pro-opiomelanocortin activation (bupropion) causes greater weight loss than placebo or monotherapy.

Design/setting: A randomized, placebo- and monotherapy-controlled, double-blind, dose-finding trial was conducted from August 2005 to December 2006 in seven U.

Rational design of a combination medication for the treatment of obesity.

Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. Here, we explore combination therapy with bupropion (BUP), a putative stimulator of melanocortin pathways, and an opioid antagonist, naltrexone (NAL), to antagonize an inhibitory feedback loop that limits sustained weight reduction. In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin (POMC) neurons in mouse brain.

Time-lapse mapping of cortical changes in schizophrenia with different treatments.

Using time-lapse maps, we visualized the dynamics of schizophrenia progression, revealing spreading cortical changes that depend on the type of antipsychotic treatment. Dynamic, 4-dimensional models of disease progression were created from 4 repeated high-resolution brain magnetic resonance imaging scans of 36 first-episode schizophrenia patients (30 men/6 women; mean age: 24.2 +/- 5.

The association between food cravings and consumption of specific foods in a laboratory taste test.

This pilot study tested the relation between food cravings and food intake in the laboratory. Participants (n=91; mean BMI=35.1 kg/m2) completed the Food Craving Inventory to measure cravings for sweets, fats, carbohydrates, and fast food fats, and a taste test consisting of four foods (jelly beans, M&M's, regular potato chips, and baked low-fat potato chips).

Zonisamide prevents olanzapine-associated hyperphagia, weight gain, and elevated blood glucose in rats.

Olanzapine (OLZ), one of the second-generation atypical antipsychotics (SGAs), has shown relative advantages in patient adherence and outcomes. However, OLZ has also been associated with a higher incidence of weight gain than most other SGAs. Excessive weight gain may in turn contribute to long-term health concerns for some individuals.

Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression.

Objectives: The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination.

Methods: Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed.

Efficacy and tolerability of an mGlu2/3 agonist in the treatment of generalized anxiety disorder.

LY354740, a potent and selective mGlu (metabotropic glutamate receptor)2/3 agonist, has shown efficacy in the treatment of generalized anxiety disorder (GAD). LY544344 is a LY354740 prodrug that increases LY354740 bioavailability. This 8-week study was designed to evaluate the efficacy, safety, and tolerability of LY544344 in the treatment of GAD.

Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study.

Objective: The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment. The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine (a dual serotonin and norepinephrine reuptake inhibitor) and escitalopram (a selective serotonin reuptake inhibitor).

Research Design And Methods: This was a randomized, double-blind, placebo- and active comparator-controlled study, in which patients (> or = 18 years) meeting DSM-IV criteria for Major Depressive Disorder (MDD) received duloxetine 60 mg once daily (QD; N = 273), escitalopram 10 mg QD (N = 274), or placebo (N = 137) for 8 weeks.

A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression.

Based on preliminary evidence of its usefulness in treatment-resistant depression (TRD), an olanzapine/fluoxetine combination (OFC) was examined in comparison with olanzapine, fluoxetine, and venlafaxine in a TRD population. In this 12-week double-blind study, 483 subjects with unipolar, nonpsychotic TRD, with historic failure on a selective serotonin reuptake inhibitor (SSRI) and prospective failure on open-label venlafaxine, were randomized to an OFC or to an olanzapine, fluoxetine, or venlafaxine monotherapy group. Venlafaxine was continued randomly in the double-blind acute phase to explore the benefits of continuation versus switching therapy.

Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol.

Background: Substantial weight gain is common with many atypical antipsychotics.

Aims: To evaluate the extent, time course and predictors of weight gain and its effect on study retention among people with first-episode psychosis treated with olanzapine or haloperidol.

Method: Survival analysis assessed time to potentially clinically significant weight gain (> or =7%) and the effect of weight gain on study retention.

Weight gain as a prognostic indicator of therapeutic improvement during acute treatment of schizophrenia with placebo or active antipsychotic.

Treatment-emergent weight gain may be a general marker of therapeutic improvement, even when improvements occur in the absence of active antipsychotic treatment. To investigate the association between treatment-emergent weight gain and therapeutic improvement across placebo and active treatments, and to examine the association between reported treatment-emergent weight changes and the treatments' reported efficacy. Data from a randomized, double-blind trial comparing treatment of schizophrenia with placebo and olanzapine were used to correlate weight change and change in psychopathology.

Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance.

Background: This 8-week, double-blind, multicenter study was undertaken to replicate, in a larger sample of patients with treatment-resistant major depressive disorder (MDD; DSM-IV criteria), the results of a pilot study of the olanzapine/fluoxetine combination.

Method: The study was begun in August 1999. The primary entry criterion was a history of failure to respond to a selective serotonin reuptake inhibitor (SSRI).

Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis.

Background: Neurocognitive deficits are severe in first-episode psychosis.

Methods: Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.

Antipsychotic drug effects on brain morphology in first-episode psychosis.

Background: Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia.

Onset of action for duloxetine 60 mg once daily: double-blind, placebo-controlled studies.

Background: It is widely believed that most antidepressant medications exhibit a delay of 2-4 weeks before clinically relevant improvement can be observed among patients. During this latency period, patients continue to be symptomatic and functionally impaired. Thus, time to onset of effect is an important attribute of a new pharmacotherapy.

The prevalence of tardive dyskinesia after a nine month naturalistic randomized trial comparing olanzapine with conventional treatment for schizophrenia and related disorders.

Aims Of The Study: To assess the impact of olanzapine versus conventional neuroleptic therapy among subjects with schizophrenia on ratings of tardive dyskinesia (TD).

Method: The naturalistic study was conducted in three psychiatric hospitals in Brazil. Patients had a diagnosis of schizophrenia and related disorders (DSMIV) and with a BPRS score>24.

Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder.

Objective: Minor depressive disorder is both common and associated with significant psychosocial impairment. This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder.

Method: One hundred sixty-two patients with minor depressive disorder were randomly assigned to receive fluoxetine or placebo in a 12-week, double-blind study; 73% (59 of 81) of the patients in each treatment group completed the study.

A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features.

The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d).

Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders.

Background: Duration of untreated psychosis (DUP) may contribute to the observed heterogeneity of the treatment response in first-episode schizophrenia.

Aims: To examine the relationship of DUP and premorbid function with clinical outcomes following up to 2 years of antipsychotic treatment.

Method: For a subsample (n=191) of subjects participating in a clinical trial, DUP and premorbid function were prospectively compared with clinical response to olanzapine or haloperidol.

Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol.

Objective: The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis.

Method: Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.

Double-blind, randomized comparison of olanzapine versus fluphenazine in the long-term treatment of schizophrenia.

This study was undertaken to evaluate the efficacy and safety of olanzapine compared with fluphenazine in the treatment of patients who met the Diagnostic and Statistical Manual, fourth edition (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder. This was a long-term (22-week), randomized, double-blind, parallel clinical trial. Sixty patients (mean age, 35.

Comparison of risperidone and olanzapine in the control of negative symptoms of chronic schizophrenia and related psychotic disorders in patients aged 50 to 65 years.

Background: This analysis compares the efficacy of risperidone and olanzapine in controlling negative and positive symptoms of chronic psychosis in older patients.

Method: Post hoc assessments were made in a subset of risperidone-treated (N = 19) and olanzapine-treated (N = 20) older patients (aged 50 to 65 years) from a large international, multicenter, parallel, double-blind, 28-week study of patients aged 18 to 65 years (N = 339) randomly assigned to receive risperidone (4-12 mg/day) or olanzapine (10-20 mg/day). Assessments were made using repeated-measures analysis.

A double-blind, randomized, placebo-controlled trial of olanzapine in the prevention of psychotic relapse.

Sustained response to antipsychotic therapy is an important outcome measure for patients with psychotic disorders. Placebo control in studies of relapse prevention contributes valuable information yet provokes much debate. This study, using placebo as a control, evaluated olanzapine's efficacy in preventing a psychotic relapse.