bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Cariprazine on Weight and Blood Pressure in Bipolar I Depression: A Real-World Study Using Electronic Medical Records
Authors: Correll Christoph U. , Laliberté François , Germain Guillaume , MacKnight Sean D. , Nguyen Huy-Binh , Parikh Mousam , Wade Sally W. , Cutler Andrew J. 
Published: April 2023

AbstractIntroductionPatients with a severe mental illness such as bipolar I disorder (BP-I) have a higher prevalence of obesity and related metabolic comorbidities than the general population. This study evaluated the impact of cariprazine on weight and blood pressure in patients with BP-I depression using electronic medical records (EMRs) from a nationally representative database.MethodsAnalyses were based on data from EMRs in the Symphony Health’s Integrated Dataverse® from March 2015 to October 2018. Patients ≥18 years of age with ≥2 cariprazine fills (first dispensing=index date) and clinical activity for ≥12 months pre-index (baseline) and ≥1 month post-index were included. Patients also had a diagnosis of BP-I depression at their most recent episode prior to cariprazine initiation. The on-treatment period spanned from the index date to the earliest of cariprazine discontinuation, a switch to another atypical or long-acting injectable antipsychotic, end of clinical activity, or end of data. Metabolic outcomes of interest were weight and blood pressure (systolic and diastolic). For each outcome, patients were required to have ≥1 measurement in both the baseline and on-treatment periods. Linear trajectories during those periods were estimated using mixed-effects models; 95% confidence intervals (CIs) were calculated using non-parametric bootstrap procedures.ResultsIn total, 1702 patients who met study eligibility criteria had ≥1 weight measurement recorded in the baseline and on-treatment periods; of these patients, 178 had bipolar I depression as their most recent episode. Patients gained an average of 2.43 kg/year during the baseline period and 0.60 (95% CI: -1.97, 3.70) kg/year during the on-treatment period. Analyses of blood pressure change (n=179) showed that cariprazine had neutral effects over the on-treatment period. Patients’ systolic blood pressure increased at 1.12 mmHg/year during baseline and decreased at -0.63 (95% CI: -3.59, 2.25) mmHg/year during the on-treatment period. For diastolic blood pressure, increases of 0.25 mmHg/year during baseline and 0.44 (95% CI: -1.65, 2.16) mmHg/year during the on-treatment period were observed.ConclusionsAlthough patient weight was increasing prior to cariprazine initiation, a neutral weight trajectory was seen with long-term cariprazine treatment among those with a most recent BP-I depression episode. Cariprazine also had minimal impact on systolic or diastolic blood pressure. Overall, these findings are consistent with prior short- and long-term studies showing that cariprazine has a neutral weight and metabolic profile.FundingAbbVie
Anticholinergics Should Not Be Used to Treat Tardive Dyskinesia: Insights From an Expert Panel of Psychiatry and Neurology Healthcare Professionals
Authors: Vanegas-Arroyave Nora , Vanderhoef Dawn , Manahan Rachel , Cicero Samantha 
Published: April 2023

AbstractIntroductionTardive dyskinesia (TD) is a persistent and often disabling hyperkinetic movement disorder associated with prolonged exposure to dopamine receptor blocking agents (e.g., antipsychotics, antiemetics). The use of anticholinergics for the treatment of movement disorders including TD is a common practice, despite a lack of supportive evidence and the potential to worsen TD. Moreover, there are now FDA-approved medications specifically indicated for TD. Two virtual meetings were held with movement disorder experts from neurology and psychiatry to better understand the real-world use of anticholinergics for TD.MethodsIn November 2020, a panel of eight experts was convened to gather insights on the challenges of differentiating TD from other drug-induced movement disorders (DIMDs) and to discuss appropriate treatments for TD and other DIMDs. A follow-up meeting was held in June 2021 to consolidate these insights. Key recommendations based on the panel discussions are presented.ResultsThe panel emphasized that while anticholinergics can help with managing some DIMDs, current evidence indicates that they are not effective in TD and may even worsen symptoms. Therefore, FDA-approved vesicular monoamine transporter 2 (VMAT2) inhibitors like valbenazine were recommended by the panel as first-line TD therapies. The panel noted that TD is often grouped under the term “extrapyramidal symptoms,” which leads to difficulty in differentiating TD from other DIMDs and the inappropriate treatment of TD with anticholinergics. The panel agreed that prophylaxis with anticholinergics is only appropriate in patients at high risk of acute dystonia. However, chronic anticholinergic use should be avoided whenever possible due to potentially serious adverse effects (e.g., cognitive difficulties) and anticholinergic burden, particularly in older patients. The potential for abuse, addiction, and diversion should also be considered when prescribing anticholinergics. Abrupt anticholinergic discontinuation can result in cholinergic rebound, which is characterized by sleep disturbances, gastrointestinal problems, urinary urgency, and manifestations of DIMDs. Thus, when used appropriately (e.g., for acute dystonia), anticholinergics should be prescribed at minimally effective doses and slowly tapered for successful discontinuation.ConclusionsThese findings align with the current TD treatment guidelines, including the lack of evidence for anticholinergic use and recommended first-line treatment with approved VMAT2 inhibitors. Conclusions from this panel highlight educational needs across HCPs on the phenomenology of DIMDs, the inappropriate use of anticholinergics for TD, TD risks and assessment, and treatment strategies for TD.FundingNeurocrine Biosciences, Inc.
Complete in vitro Dissolution of Valbenazine as Either Whole Capsules or Crushed Capsule Contents
Authors: Hebert Mello , Moore Richard , Jen Eric , Siegert Scott 
Published: April 2023

AbstractIntroductionTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with exposure to antipsychotics and other dopamine receptor blocking agents. Three valbenazine capsule strengths (40 mg, 60 mg, 80 mg) are approved for the once-daily treatment of TD. However, some patients with TD, especially in elderly populations, have trouble swallowing due to orolingual movements. This study was conducted to evaluate two different dissolution methods for valbenazine: whole intact capsules versus crushed capsule contents.MethodsSamples were prepared using two commercial lots (Lot-A, Lot-B) for two doses (40 mg, 80 mg), with six replicate samples per lot and dose. The whole capsules were weighed, put into a sinker, and added to a dissolution bath containing 900 mL of 0.1N HCl at 37±0.5° Celsius. Testing on the crushed capsule contents commenced after opening the capsules, weighing and crushing the contents, and transferring the contents to the dissolution bath. Samples were collected (at 10, 15, 20, 30, 45, and 60 min) with a paddle speed of 50 rpm and analyzed using high performance liquid chromatography. Standards were prepared at nominal concentrations of 0.044 mg/mL (for 40 mg) and 0.089 mg/mL (for 80 mg).ResultsCapsules were opened easily by manual manipulation, and contents were crushed easily between spoons. Very rapid (>85% in 15 min) and complete drug release was observed in all samples, independent of capsule strength (40 mg, 80 mg) or preparation (whole intact capsule or crushed capsule contents). For 40-mg capsules, average percent release at first and last collection timepoints were as follows (whole vs crushed): 10 min (98.4% vs 98.6% [A], 93.7% vs 97.6% [B]); 60 min (102.3% vs 100.5% [A], 100.9% vs 100.6% [B]). Results for 80-mg capsules were as follows: 10 min (98.2% vs 99.6% [A], 99.4% vs 97.9% [B]); 60 min (102.0% vs 101.6% [A], 103.2% vs 100.9% [B]).ConclusionsCrushing the capsule contents did not impact the in vitro dissolution performance of valbenazine. Many patients with TD, particularly elderly patients, have difficulty swallowing and may benefit from alternative delivery methods for valbenazine, especially if other TD medications cannot be crushed. More research is needed to better understand if and how crushing the capsule contents of valbenazine affects their stability when mixed with food or delivered through a feeding tube.FundingNeurocrine Biosciences, Inc.
Genetic Behavioral Trait Assessment Paired With Personalized Recommendations and Coaching to Support Mental Health and Wellness
Authors: Krause David , VanDorn Daniel , Nguyen Harris , Amato Russel 
Published: April 2023

AbstractBackgroundGenetics, environment, and lifestyle each contribute to human behaviors. We have developed a direct-to-consumer genetic assay (Mental Health Map) that allows users to explore their genetic behavioral predispositions and potential interventions that may positively influence mental health and wellness. Based on preliminary consumer feedback suggesting increased desire to take action on their mental health and wellness, we initiated a pilot study to assess several measures of mental health and self-care in individuals both before and after reviewing their Mental Health Map.MethodsThis was a virtual case series in adults who purchased a Mental Health Map. Subjects served as their own control based on survey responses leading up to genetic testing and up to 7 weeks after an introductory coaching session. Coaching included a demonstration of how to navigate the interactive online report, discussion of key results, and provision of additional external resources as appropriate. The co-primary measures were changes in quality of life as measured by WHO-5, report of initiating a discussion or seeking mental health care with a health care provider, report of initiating and sustaining positive lifestyle changes, and subjective improvements in stress management, sleep quality, mood, focus, and social interactions. Secondary measures were changes in GAD-7 and PHQ-9.ResultsTwenty-seven individuals completed the study. Average WHO-5 at baseline was 41.2 which numerically increased to 48.3 at week 7, suggesting improved quality of life, but this effect was not statistically significant. 42.3% of individuals were in treatment with a mental health provider at the time of survey. Of those not in treatment, 33.3% were actively seeking professional mental healthcare prompted by the coaching session. At week 6, 87% of survey respondents (n=15) asserted that they continued to make lifestyle changes that improved stress; 74% made changes to improve mood and 80% made changes that improved their habits. Percentage of respondents who reported lifestyle changes to improve sleep, focus, and social interactions were all less than 70%. In secondary outcomes, average GAD-7 at baseline was 8.9 and decreased to 6.7 at week 7, while PHQ-9 averaged 10.3 at baseline and decreased to 7.5 at week 7. Neither of the secondary outcome measures achieved a statistically significant difference.ConclusionDespite the small patient population, this pilot study provides proof-of-concept that Mental Health Map and the accompanying coaching session encourages participants to make positive lifestyle changes and prompts pursuit of a healthcare professional. We also saw numerical trends toward modest improvements in quality of life, anxiety, and depression symptoms, although these differences were not statistically significant, and may require larger sample sizes.FundingGenomind
Long-Term Lumateperone Treatment in Bipolar Disorder: Six-Month Open-Label Extension Study
Authors: Tohen Mauricio , Durgam Suresh , Kozauer Susan , D’Souza Ian , Chen Richard , Mates Sharon 
Published: April 2023

AbstractIntroductionApproved therapeutics for bipolar depression are associated with a range of undesirable side effects. Lumateperone (LUMA), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. The efficacy of LUMA in bipolar depression was previously established in two Phase 3 trials, as monotherapy (NCT03249376) and as adjunctive to lithium or valproate (NCT02600507).A recent Phase 3 multi-center trial, Study 401 (NCT02600494) investigated the efficacy and safety of LUMA in bipolar depression and comprised a 6-week, randomized, double-blind, placebo-controlled period and a 6-month open-label extension (OLE) period. Here, we report the results of the OLE period, examining long-term safety.MethodsPatients, aged 18–75 years, with a clinical diagnosis of bipolar I or II disorder who were experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and a Clinical Global Impression Scale-Bipolar Version, Severity [CGI-BP-S] score ≥4) were eligible for Study 401. Patients who completed the double-blind study were eligible for direct rollover into the OLE or were re-screened if completing the double-blind period prior to the initiation of the OLE. During the OLE, LUMA 42 mg was administered once-daily in the evening for 25 weeks.The primary objective was safety and tolerability of LUMA as measured by incidences of adverse events (AEs) and changes in laboratory parameters, cardiometabolic measurements, electrocardiogram (ECG), and vital signs. The secondary objective was improvement/maintenance of symptoms of depression as measured MADRS and CGI-BP-S Total scores.ResultsA total of 127 patients were enrolled in the OLE, with 74 (58.3%) completing the study. Treatment-emergent AEs (TEAEs) occurred in 73 patients (57.5%) with 54 (42.5%) experiencing a drug-related TEAE. TEAEs that occurred in ≥5% of patients were headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability. Most TEAEs were mild or moderate in severity. Extrapyramidal-symptom-related TEAEs were rare. Most patients who had normal metabolic laboratory values at baseline remained normal during the treatment period. Mean changes in blood pressure, pulse rate, ECG, and body morphology were minimal. Symptoms of depression improved as measured by the mean change from baseline to Day 175 in MADRS Total score (−8.9) and CGI-BP-S Total score (−2.3).ConclusionIn patients with bipolar depression, long-term LUMA treatment was generally well tolerated with low risk of extrapyramidal symptoms, weight gain, and cardiometabolic effects. These data further support the safety, tolerability, and effectiveness of LUMA in patients with bipolar depression.FundingIntra-Cellular Therapies, Inc.
Effect of Lumateperone (ITI-007) on Quality of Life and Functional Disability in the Treatment of Bipolar Depression
Authors: Edwards John B , Durgam Suresh , Kozauer Susan G , Jain Rakesh , McIntyre Roger S 
Published: April 2023

AbstractIntroductionIn patients with bipolar disorder, depression symptoms are associated with greater reduction in function and quality of life than hypomania/mania symptoms. Lumateperone (LUMA), is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder.In a recent phase 3 clinical trial (Study 404, NCT03249376) in people with bipolar depression, LUMA 42 mg monotherapy significantly improved symptoms of depression compared with placebo (PBO). This analysis of Study 404 investigated the effects of LUMA on functional disability and quality of life as measured using the secondary outcome measure, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF).MethodsPatients (18–75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score ≥4) were randomized to LUMA 42 mg or PBO orally, once daily in the evening for 6 weeks. The primary endpoint was the change from baseline to Day 43 in MADRS Total score, analyzed using a mixed-effects model for repeated measures (MMRM) approach in the intent-to-treat population (ITT). This post hoc analysis evaluated the mean change from baseline to Day 43 in the Q-LES-Q-SF individual item scores using an analysis of covariance with last observation carried forward (ANCOVA-LOCF) in the ITT. Categorical shifts in individual items were also analyzed.ResultsThe ITT comprised 376 patients (LUMA 42 mg, 188; PBO, 188). Patients in the LUMA 42 mg group had significantly greater improvement on MADRS Total score change from baseline to Day 43 compared with PBO (least squares mean difference vs PBO [LSMD], −4.585; 95% CI, −6.344 to −2.826; effect size vs PBO [ES], −0.56; P<.0001). LUMA 42 mg treatment significantly improved Q-LES-Q-SF Total score from baseline to Day 43 compared with PBO (LSMD, 2.9; 95% CI, 1.15 to 4.59; P=.001).The Q-LES-Q-SF items with the lowest mean scores at baseline in both groups were mood, leisure time activities, and sexual drive, interest, and/or performance. By Day 43, LUMA 42 mg treatment significantly improved 8 of the 14 items in the Q-LES-Q-SF (P<0.05). Overall life satisfaction also significantly improved with LUMA treatment (P=.0016). The largest improvements with LUMA 42 mg compared with PBO (ES>0.3,) were seen for the ability to function in daily life, family relationships, household activities, leisure time activities, and mood (all LSMD=0.3; all P<.01).ConclusionIn patients with bipolar depression, treatment with LUMA 42 mg compared with PBO significantly improved patient quality of life and functional impairment. These results support LUMA 42 mg as treatment of MDEs associated with bipolar I or bipolar II disorder in adults.FundingIntra-Cellular Therapies, Inc.
A 16-Week Open-Label Study of the Effects of Treatment With Pimavanserin on Activities of Daily Living in Subjects With Parkinson’s Disease Psychosis
Authors: Evidente Virgilio G. H. , DeKarske Daryl , Coate Bruce , Naujoks Karla , Abler Victor 
Published: April 2023

AbstractIntroductionAccurate assessment of disability associated with Parkinson’s Disease Psychosis (PDP) is essential and has been poorly studied. Patients often have poor insight on impact of PDP on daily function. This phase 4 study is the first to evaluate the impact of pimavanserin on activities of daily living (ADL) in PDP patients.MethodsEligible PDP patients entered a 16-week single-arm, open-label study of oral pimavanserin (34 mg) taken once daily. Primary endpoint (modified Functional Status Questionnaire [mFSQ]) and secondary endpoints (MDS-UPDRS I & II; Schwab and England ADL; CGI-S, CGI-I, and PGI-I) were measured as change from baseline to Week 16 using mixed-effects model for repeated measures (MMRM) and least-squares means (LSM).Results29 patients were treated with pimavanserin, of which 24 (82.8%) completed the study. Treated patients demonstrated significant improvements in LSM (SE) mFSQ score change from baseline to Week 12 (11.5 [2.44]) and Week 16 (14.0 [2.50]; both p<0.0001). Significant improvements (p<0.05) were also observed for all secondary outcomes at Week 16 (MDS-UPDRS Part I: -6.3 [0.97]; MDS-UPDRS Part II: -2.6 [0.98]; CGI-S: -1.5 [0.25]; CGI-I: 1.9 [0.17]; PGI-I: 2.0 [0.22], except for Schwab and England ADL. No new safety signals were observed.ConclusionFunctional outcomes and psychosis measures improved in PDP patients treated with pimavanserin, with safety findings consistent with previous studies. Our findings highlight the positive effect of pimavanserin in improving ADLs in patients with PDP.FundingAcadia Pharmaceuticals Inc.
Safety And Efficacy of Aripiprazole 2-Month Ready-to-Use 960 mg in Adult Patients With Schizophrenia
Authors: Such Pedro , Yildirim Murat , Madera-McDonough Jessica , Citrome Leslie 
Published: April 2023

AbstractBackgroundAripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months. This 32-week trial evaluated the safety, pharmacokinetics, and efficacy of multiple-dose administration of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (BP-I), versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole [indication varies by country]). Safety and efficacy outcomes in the subpopulation of patients with schizophrenia are reported here.MethodsPatients with schizophrenia were randomized to receive Ari 2MRTU 960 every 56±2 days or AOM 400 every 28±2 days. Safety and tolerability assessments included adverse event (AE) reporting, Visual Analogue Scale [VAS] scores (scale range: 0–100) for patient-reported injection site pain, and extrapyramidal symptom (EPS) monitoring. Efficacy was evaluated at Week 32 using mean (standard deviation [SD]) Clinical Global Impression – Improvement (CGI-I) score, and mean (SD) change from baseline in Clinical Global Impression – Severity (CGI-S) score, Subjective Well-being under Neuroleptic Treatment – Short Form [SWN-S] Total score, and Positive and Negative Syndrome Scale (PANSS) Total score.ResultsStudy completion rate was 79.3% (73/92 patients) in the Ari 2MRTU 960 group and 67.7% (63/93 patients) in the AOM 400 group. Demographics and disease characteristics were well balanced between groups at baseline (mean [SD] PANSS Total score: Ari 2MRTU 960, 62.0 [13.5]; AOM 400, 61.8 [13.5]; mean (SD) CGI-S score: Ari 2MRTU 960, 3.3 [0.9]; AOM 400, 3.1 [0.9]). Treatment-emergent AE (TEAE) incidence was 66.3% with Ari 2MRTU 960 and 63.4% with AOM 400. The most frequent TEAEs were increased weight (Ari 2MRTU 960, 21.7%; AOM 400, 18.3%) and injection site pain (Ari 2MRTU 960, 15.2%; AOM 400, 9.7%). Mean (SD) VAS score for pain after last injection was 1.5 (4.58) with Ari 2MRTU 960 and 1.3 (2.79) with AOM 400. Minimal change was seen in EPS in either group. At Week 32, mean (SD) CGI-I score was similar between groups (Ari 2MRTU 960, 3.5 [1.0]; AOM 400, 3.6 [0.9]). Minimal change from baseline was seen at Week 32 in CGI-S score and SWN-S Total score. There was no clinically meaningful difference between the groups for PANSS Total score (difference of least squares mean change from baseline [95% confidence interval]: -0.9 [-3.5, 1.8]; p=0.5154).ConclusionsIn patients with schizophrenia, administration of Ari 2MRTU 960, as compared with AOM 400, was generally well tolerated, and clinical stability was maintained during the study.FundingOtsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).