Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials.

In the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials, xanomeline and trospium chloride (formerly known as KarXT) significantly improved symptoms of schizophrenia and was generally well tolerated. We pooled data from the EMERGENT trials to further characterize the efficacy of xanomeline/trospium and provide sufficient statistical power to analyze responses in participant subgroups. In pooled analyses, xanomeline/trospium significantly improved Positive and Negative Syndrome Scale (PANSS) total score at week 5 versus placebo (least squares mean difference, -9.

Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials.

Background: Currently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M /M preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms.

Functioning and Cognition in Patients with Schizophrenia After Initiating Treatment with Aripiprazole Lauroxil: Secondary Outcomes and Post Hoc Analysis.

Background: Clinical practice guidelines support efforts to improve functioning in patients with schizophrenia. Discrepancies in the perception of cognitive status between clinicians, patients with schizophrenia, and their caregivers have been associated with impaired functional abilities in patients; medication side effects might worsen both cognition and daily functioning. We assessed daily/social functioning and cognition in stable patients with schizophrenia who switched to the long-acting injectable (LAI) antipsychotic aripiprazole lauroxil (AL).

Handwriting Kinematics in Patients with Schizophrenia Treated with Long-Acting Injectable Atypical Antipsychotics: Results From the ALPINE Study.

Handwriting kinematics (HWKs) were assessed in the randomized controlled ALPINE study of 2 long-acting injectable antipsychotics started during an acute exacerbation of schizophrenia. This exploratory analysis examined the relationship between baseline HWKs and response to acute antipsychotic treatment. Adults with acute schizophrenia were assigned to aripiprazole lauroxil or paliperidone palmitate (groups combined for this analysis).

Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study.

Background: A randomized, controlled, phase 3b study (ALPINE) evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) using a 1-day initiation regimen in patients hospitalized for an acute exacerbation of schizophrenia. Paliperidone palmitate (PP) was used as an active control. Exploratory endpoint assessments included severity of illness, positive and negative symptoms, quality of life, caregiver burden, and satisfaction with medication.

Analysis of prolactin and sexual side effects in patients with schizophrenia who switched from paliperidone palmitate to aripiprazole lauroxil.

One strategy to address hyperprolactinemia and associated sexual side effects in patients receiving antipsychotics is switching to an antipsychotic not associated with prolactin elevation (eg, aripiprazole). This post hoc analysis assessed prolactin concentrations and sexual side effects in an open-label prospective study of switching long-acting injectable antipsychotics from paliperidone palmitate (PP) to aripiprazole lauroxil (AL). Serum prolactin was measured throughout the study.

A Comparison of Volatile Anesthesia and Total Intravenous Anesthesia (TIVA) Effects on Outcome From Cardiac Surgery: A Systematic Review and Meta-Analysis.

Objective: The primary objective of this study was to compare one-year mortality in patients undergoing cardiac surgery with volatile anesthesia or total intravenous anesthesia (TIVA). Secondary objectives were to compare in-hospital and 30-day mortality, postoperative levels of creatine kinase (CK-MB) and cardiac troponin, and durations of tracheal intubation, intensive care unit (ICU) and hospital stays.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Beyond 52-Week Long-Term Safety: Long-Term Outcomes of Aripiprazole Lauroxil for Patients With Schizophrenia Continuing in an Extension Study.

Objective: To describe the long-term safety, tolerability, and symptom trajectory with the long-acting injectable antipsychotic aripiprazole lauroxil (AL) in patients with DSM-5-diagnosed schizophrenia followed for up to 180 weeks (3.5 years).

Methods: Long-term safety of 2 fixed doses of AL (441 or 882 mg every 4 weeks) was assessed during up to 180 weeks (3.

Efficacy and Safety of a 2-Month Formulation of Aripiprazole Lauroxil With 1-Day Initiation in Patients Hospitalized for Acute Schizophrenia Transitioned to Outpatient Care: Phase 3, Randomized, Double-Blind, Active-Control ALPINE Study.

Objective: Evaluate efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) with 1-day initiation during hospitalization for acute exacerbation of schizophrenia followed by transition to outpatient care.

Methods: The phase 3b double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study was conducted from November 2017 to March 2019. Adults with acute schizophrenia according to DSM-5 criteria were randomized (1:1) to AL (AL NanoCrystal Dispersion + oral aripiprazole 30 mg, day 1; AL 1,064 mg, day 8 and every 8 weeks [q8wk]) or paliperidone palmitate (PP 234 mg, day 1; PP 156 mg, day 8 and then q4wk) for 25 weeks.

Results from a long-term open-label extension study of adjunctive buprenorphine/samidorphan combination in patients with major depressive disorder.

Buprenorphine/samidorphan (BUP/SAM; ALKS 5461) is an investigational opioid system modulator for the adjunctive treatment of patients with major depressive disorder (MDD), who did not respond adequately to prior antidepressant therapy (ADT). FORWARD-2, an open-label extension study, assessed long-term safety and tolerability of adjunctive BUP/SAM treatment in these patients. Patients from four short-term trials and de novo patients were enrolled; all had confirmed MDD and a current major depressive episode lasting 2-24 months.

Social and functional outcomes with two doses of aripiprazole lauroxil vs placebo in patients with schizophrenia: a post-hoc analysis of a 12-week phase 3 efficacy study.

To assess the effect of the long-acting antipsychotic aripiprazole lauroxil (AL) on social and functional outcomes compared with placebo in patients with acute schizophrenia, a post-hoc analysis was conducted. Patients with acute schizophrenia were enrolled in a 12-week, double-blind, placebo-controlled efficacy trial, and randomized 1:1:1 to receive AL 441 mg, AL 882 mg, or placebo every 4 weeks. Changes in social functioning using the 6- and 4-item Positive and Negative Syndrome Scale (PANSS) Prosocial subscales were evaluated.

Switching patients with schizophrenia from paliperidone palmitate to aripiprazole lauroxil: A 6-month, prospective, open-label study.

We assessed the effectiveness of switching from paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) to aripiprazole lauroxil (AL). Prospective, 6-month study in patients with schizophrenia with residual symptoms or intolerance with PP/RLAI. Effectiveness assessed via all-cause and medication-related discontinuation; CGI-S/BPRS and adverse event monitoring assessed efficacy/tolerability, respectively.

Long-term safety and tolerability of aripiprazole lauroxil in patients with schizophrenia.

Objective: Safety and tolerability of long-term treatment with the long-acting antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with schizophrenia.

Methods: This was an international, multicenter, phase 3, 52-week safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4 weeks). Safety endpoints included adverse events (AEs) and extrapyramidal symptoms (EPS) including akathisia, injection-site reactions (ISRs), and clinically relevant changes in metabolic and endocrine values.

Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial.

Background: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers.

Objective: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD.

Effect of aripiprazole lauroxil on agitation and hostility in patients with schizophrenia.

This study aimed to evaluate the effects of aripiprazole lauroxil on hostility and aggressive behavior in patients with schizophrenia. Patients aged 18-70 years with a diagnosis of schizophrenia and currently experiencing an acute exacerbation or relapse were randomized to intramuscular (IM) aripiprazole lauroxil 441 mg (n=207), 882 mg (n=208), or placebo (n=207) for 12 weeks. In post-hoc analyses, hostility and aggression were assessed by the Positive and Negative Syndrome Scale (PANSS) Hostility item (P7) and a specific antihostility effect was assessed by adjusting for positive symptoms of schizophrenia, somnolence, and akathisia.

Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia.

Previous trials have shown promising effects of intranasally administered insulin for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). These trials used regular insulin, which has a shorter half-life compared to long-lasting insulin analogues such as insulin detemir. The current trial examined whether intranasal insulin detemir improves cognition or daily functioning for adults with MCI or AD.

Deconstructing racial differences: the effects of quality of education and cerebrovascular risk factors.

Objectives: To evaluate the effects of vascular conditions and education quality on cognition over time in White and African American (AA) older adults.

Method: We investigated cross-sectional and longitudinal racial differences in executive functioning (EF) and memory composites among Whites (n = 461) and AAs (n = 118) enrolled in a cohort study. We examined whether cerebrovascular risk factors and Shipley Vocabulary scores (a proxy for education quality) accounted for racial differences.

Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease.

A previous clinical trial demonstrated that four months of treatment with intranasal insulin improves cognition and function for patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), but prior studies suggest that response to insulin treatment may differ by sex and ApoE ε4 carriage. Thus, responder analyses using repeated measures analysis of covariance were completed on the trial's 104 participants with MCI or AD who received either placebo or 20 or 40 IU of insulin for 4 months, administered by a nasal delivery device. Results indicate that men and women with memory impairment responded differently to intranasal insulin treatment.

Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.

Objective: To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease (AD).

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Clinical research unit of a Veterans Affairs medical center.

Personality trait levels within older couples and between-spouse trait differences as predictors of marital satisfaction.

In this study of 125 older couples married for an average of 34 years, multilevel models were computed to simultaneously examine intra-couple personality trait averages and between-spouse trait similarity as predictors of marital satisfaction. Our findings suggest that higher intra-couple levels of extraversion predict marital satisfaction, both husbands and wives. In addition, between-spouse similarity in openness to experience appears associated with higher levels of marital satisfaction as reported by husbands; concomitantly, between-spouse similarity in agreeableness predicts wives' marital satisfaction.

Functions of reminiscence and the psychological well-being of young-old and older adults over time.

Existing cross-sectional research demonstrates an association between reminiscence functions and well-being in later life. The results of this study replicate and extend previous findings in separate participant samples above and below 70 years of age. Findings suggest a link between reminiscence functions and psychological well-being, and indirectly between reminiscence and well-being 16 months thereafter.

Psychological resilience predicts depressive symptoms among spouses of persons with Alzheimer disease over time.

This study examines the three facets of psychological resilience (i.e., perceived control, commitment to living, challenge versus stability) as predictors of depressive symptoms over time among spousal caregivers of persons with Alzheimer disease; these resilience factors were considered over and above dementia-related and socio-demographic control variables.

Knowing me-knowing you: Reported personality and trait discrepancies as predictors of marital idealization between long-wed spouses.

In previous research, marital idealization has emerged as a significant predictor of adaptation to widowhood, the psychological well-being of spouses of persons with dementia, and the physical health of older married adults over time. Despite the adaptive value of marital idealization, conceptual confusion regarding this phenomenon persists. To this end, the present study examines the degree to which marital idealization is predicted by personality traits relative to partner perceptions of their spouse's personality, and discrepancies between self- vs.