PANSS Individual Item and Marder Dimension Analyses From a Pivotal Trial of RBP-7000 (Monthly Extended-Release Risperidone) in Schizophrenia Patients.

Positive and Negative Syndrome Scale (PANSS) data from a pivotal phase 3 study in participants with schizophrenia of RBP-7000, a recently marketed long-acting subcutaneous injectable risperidone formulation, were examined to determine if dose-response relationships existed for different items of the PANSS. Changes in the 30 PANSS items were analyzed individually and using the 5 factor-analysis-derived dimensions defined by Marder and colleagues. Subgroups of patients who could benefit from the RBP-7000 120 mg dose were investigated.

A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder.

Background: Buprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine.

Methods: We examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs).

Monthly Extended-Release Risperidone (RBP-7000) in the Treatment of Schizophrenia: Results From the Phase 3 Program.

Purpose/background: The Phase 3 program for RBP-7000, a once-monthly subcutaneous (SC) extended-release risperidone formulation approved for treatment of schizophrenia, consisted of a double-blind placebo-controlled trial (previously reported) and a 52-week open-label study of monthly RBP-7000 120 mg. The primary objective of the open-label study was to evaluate the long-term safety and tolerability of RBP-7000 in adults with schizophrenia. A secondary objective was to assess long-term maintenance of effectiveness.

Evaluation of the Effects of a Monthly Buprenorphine Depot Subcutaneous Injection on QT Interval During Treatment for Opioid Use Disorder.

Extensive 12-lead electrocardiogram monitoring and drug concentrations were obtained during development of BUP-XR, a monthly subcutaneous injection for the treatment of opioid use disorder (OUD). Matched QT and plasma drug concentrations (11,925) from 1,114 subjects were pooled from 5 studies in OUD. A concentration-QT model was developed, which accounted for confounding factors (e.

Pharmacologically, are smokers the same as non-smokers?

Growing evidence suggests that there are subpopulations of daily smokers ranging from light infrequent users to heavy daily users. In the present review we will investigate whether these differences can be explained by factors such as social context, responsiveness to environmental cues, personality traits, neurochemical and pharmacogenetic differences. We will also assess how controlled abstinence and free choice smoking paradigms in a human laboratory setting may help identify and characterize these differences and what can be learned from these models to accurately predict clinical efficacy in the later phase testing of new chemical entities for the treatment of smoking dependence.

Occupancy of brain dopamine D3 receptors and drug craving: a translational approach.

Selective dopamine D(3) receptor (D(3)R) antagonists prevent reinstatement of drug-seeking behavior and decrease the rewarding effects of contextual cues associated with drug intake preclinically, suggesting that they may reduce drug craving in humans. GSK598809 is a selective D(3)R antagonist recently progressed in Phase I trials. The aim of this study was to establish a model, based on the determination of the occupancy of brain D(3)Rs (O(D(3))(R)) across species, to predict the ability of GSK598809 to reduce nicotine-seeking behavior in humans, here assessed as cigarette craving in smokers.

Evidence for the efficacy of duloxetine in treating mild, moderate, and severe depression.

Clinicians need to know whether duloxetine is effective in patients across a broad range of depressive symptoms and depression severity. Data were pooled from nine randomized, double-blind, placebo-controlled studies in major depressive disorder (total N=2227) comparing duloxetine (40-120 mg/day) with placebo for 8-9 weeks. Patients were retrospectively stratified by baseline score on the HAMD17 into mild (< or =19; n=682), moderate (n=1099), or severe (> or =25; n=446) groups.

Duloxetine for the treatment of major depressive disorder: a closer look at efficacy and safety data across the approved dose range.

Objective: This analysis focuses on efficacy and safety data obtained from studies of duloxetine for the treatment of major depressive disorder (MDD) within the approved dose range of 40-60 mg/day.

Method: Efficacy and safety data were obtained from the acute phase portions of four randomized, double-blind, placebo-controlled clinical trials in patients meeting DSM-IV criteria for MDD. In Studies 1 and 2, patients were randomized to duloxetine 60 mg once daily (QD) (n=123 [Study 1]; n=128 [Study 2]) or placebo (n=122 [Study 1]; n=139 [Study 2]) for 9 weeks.

Antipsychotic drug interactions with specific [3H]ketanserin binding sites in membrane fragments derived from human prefrontal cortex and human amygdala.

Two regions of the brain potentially significant for psychopathology in schizophrenia are the prefrontal cortex and the amygdala. Antipsychotic compounds bind at serotonin receptors in human prefrontal cortex. We hypothesized that the serotoninergic antagonist [3H]ketanserin would label similar sets of binding sites in these two brain regions.

Factors Affecting Pro- and Anti-Oxidant Properties of Fragments of the b-Protein Precursor (bPP): Implication for Alzheimer's Disease.

Oxidative stress may have a key pathogenetic role in neurodegenerative diseases including Alzheimer's disease (AD). While there is evidence that some amyloid-b (Ab) peptides can initiate oxidative stress at micromolar doses, there is also some evidence that oxidative stress increases the concentration of the b-protein precursor (bPP) and the potential for increased formation of the Ab peptides. The following studies were performed to test the hypothesis that fragments of bPP could be antioxidants and hence that oxidative stress might be an early event in AD.

Increased Expression but Reduced Activity of Antioxidant Enzymes in Alzheimer's Disease.

A growing body of data suggests that free radicals are involved in the pathogenesis of Alzheimer's disease (AD). Increased expression of antioxidant enzymes, such as superoxide dismutase (SOD), and their co-localization to senile plaques and dystrophic neurites have established a firm association between free-radical mediated injury and the disease neuropathology. While several studies have confirmed these findings, there is conflicting information regarding the activity of some of the enzymes.