bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of External Factors in the Severity of Dissociation Experienced by Treatment- Resistant Depression Patients Following Esketamine Administration
Authors: Vento-Correa Maria M. , Meyyappa Vidhya , Augsten Alberto , Sotelo Samantha , Abramovici Gil 
Published: January 2025

IntroductionEsketamine nasal spray is an NMDA receptor antagonist which is FDA approved, in conjunction with an oral antidepressant, for treatment- resistant depression (TRD) in adults. Dissociation is a well-known side effect to treatment and can be measured using the CADSS (Clinician Administered Dissociative States Scale). To date, patient specific factors that may contribute to the severity of dissociation have not been described.MethodsThis case series describes two patients receiving treatment with 84-mg esketamine nasal spray twice weekly in an outpatient clinic for TRD who experienced an episode of significant dissociation several months into their treatments. History obtained prior to esketamine treatment included an assessment for any recent stressors. CADSS score was assessed posttreatment.ResultsCase 1 was a 55-year-old female who had been receiving esketamine for over two months who presented to the clinic complaining of recent sleep-deprivation while caring for her newborn grandchild. Patient experienced extreme dissociation following administration of esketamine, verbalizing that she felt “very big” and began twitching, grimacing, moaning, and repeating nonsensical statements. CADSS score after treatment was 27. Case 2 involves a 59-year-old female with a remote history of sexual trauma who was four months into esketamine treatments when she presented to the clinic feeling sad after listening to another sexual assault victim’s testimony on social media prior to treatment. Shortly after receiving esketamine, she began experiencing a flashback to previous trauma and screaming loudly. CADSS score after treatment was 21. Although both patients reported a history of dissociation with esketamine treatments in the past, they both reported that the level of dissociation they experienced during the above sessions was far more severe.ConclusionsSevere episodes of dissociation during treatment with esketamine in patients with TRD may be associated with patient specific factors. Assessing patients for the presence of recent stressors or changes to their routine prior to each treatment session may help healthcare professionals predict the risk of severe dissociation and allow providers to better prepare to support patients during these experiences.FundingNo Funding
Diagnosis and Symptoms of Narcolepsy from the Patient Perspective: Results from In-Depth Qualitative Interviews
Authors: Doane Michael J. , O’Connor Meaghan , Lauher-Charest Miranda , Waldman Laura Tesler , Williams Wilbur P. 
Published: January 2025

IntroductionNarcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness (EDS), among other symptoms. Previous studies of narcolepsy have largely relied on quantitative methods, providing limited insight into the patient experience. This study used qualitative interviews to better understand this rare condition.MethodsPatients with narcolepsy (types 1 [NT1] and 2 [NT2]) were recruited using convenience and snowball sampling. Trained qualitative researchers conducted hour-long, individual interviews. Interview transcripts were coded and thematically analyzed using inductive and deductive approaches.ResultsTwenty-two adults with narcolepsy (NT1=12; NT2=10) participated (average age: NT1=35; NT2=44). Most were female (NT1=83%; NT2=70%) and white (NT1=75%; NT2=60%). Average times since diagnosis were 7 years (NT1) and 11 years (NT2).At disease onset, symptoms experienced included EDS (NT1=83%; NT2=80%)—sometimes involving sleep attacks (NT1=35%; NT2=50%)—fatigue (NT1=42%; NT2=30%), oversleeping (NT1=33%; NT2=20%), and cataplexy (NT1=42%). Participants sought a diagnosis from healthcare professionals including sleep specialists, neurologists, pulmonologists, psychiatrists, and primary care physicians. Many participants reported receiving a narcolepsy diagnosis >10 years after symptom onset (NT1=50%; NT2=60%). During that time, patients reported misdiagnoses, including depression, sleep apnea, and attention-deficit/hyperactivity disorder.Common symptoms included EDS (NT1=100%; NT2=90%), cognitive impairment (NT1=92%; NT2=100%), and fatigue (NT1=75%; NT2=90%). All participants with NT1 reported cataplexy. Participants rated these symptoms as among the most bothersome.ConclusionsStudy results provide descriptions of narcolepsy symptoms and the often challenging journey toward seeking a diagnosis. By using patient-centered, qualitative methods, this study fills a gap by providing additional insights into the patient experience of narcolepsy.FundingAlkermes, Inc.
Recognizing Practice Gaps Schizophrenia Diagnosis and Treatment: Results of a CME Accredited Survey
Authors: Guevara Natalie , Lubarda Jovana , Arnaud-Hevi Lisette 
Published: January 2025

BackgroundSchizophrenia is a severe chronic illness that affects approximately 1% of the population worldwide and is estimated to affect at least 3.5 million people in the United States. Although a range of antipsychotic medications exists for treating schizophrenia, outcomes have historically been poor, and evidence confirms that clinicians remain challenged to individualize treatment for patients living with schizophrenia.This study was designed to understand the clinical practice gaps and perspectives of clinicians related to managing schizophrenia and help inform the development of education and tools to improve clinician knowledge, competence and confidence.MethodsA survey instrument containing 24 multiple choice, knowledge and case-based questions was used to assess participants’ knowledge, attitudes, and confidence in the management of Schizophrenia. The survey was available online to US and global physicians without monetary compensation or charge. Respondent confidentiality was maintained, and the responses were de-identified and aggregated prior to analyses. Questions were grouped into clinical themes and analyzed. Data were collected from 8/11/2022 to 12/14/2022.ResultsIn total, 560 psychiatrists, and 94 Primary Care Physicians answered all questions in the assessment. Physicians demonstrated gaps in the following areas:Correct AnswerClinical ThemePsychiatrists(n=560)Primary Care Physicians(n=94)Diagnosis and Assessment54%38%MOA of novel and emerging therapies39%32%Treatment nonresponse67%55%Individualizing treatment50%38%ConclusionThis educational research on assessment of clinical practices revealed important knowledge and competence gaps amongst psychiatrists and PCPs who manage patients with Schizophrenia. Addressing these gaps is critical to improving the management of patients.FundingMedscape Education, Cerevel Therapeutics
Impact of Progressive Muscle Relaxation on Psychological Symptoms on an Inpatient Psychiatric Unit
Authors: Farris Penelope C. , Lynch Sean T. , Groenendaal Emily , Klepacz Lidia , Meyers Bambina , Ferrando Stephen J. 
Published: January 2025

ObjectivesTo examine the effectiveness of short-term progressive muscle relaxation therapy in reducing symptoms of depression, anxiety, and aggression/agitation, in patients on an inpatient psychiatric unit. Additionally, to determine the impact of clinical and sociodemographic factors on its effectiveness.MethodsPsychiatric inpatients at a private, community-based psychiatric hospital were invited to participate in a progressive muscle relaxation activity and filled out pre- and post-activity surveys querying symptoms of depression, anxiety, and aggression/agitation, using a created Likert scale.ResultsThe 57 participants in this study showed an average decrease in every symptom domain, including -0.93 in agitation/aggressive symptoms (p<0.001), -2.14 in depressive symptoms (p<0.001), and -1.81 in anxiety symptoms (p<0.001). While diagnosis did not appear to be significantly related to change in score, patients with different primary diagnoses had changes in different symptom domains, with patients with Bipolar Disorder having statistically significant changes in aggression (-1.57, p=0.012) and depression (-2.36, p<0.001), but not in anxiety. Patients with Depression had significant changes in depression (-2.08, p<0.001) and anxiety (-1.96, p<0.001) but not in aggression/agitation, while patients with a Schizophrenia spectrum illness had changes in depression alone (-2.33, p=0.008). Sociodemographic variables had no significant impact.ConclusionsThe findings in this study indicate that a short-term progressive muscle relaxation intervention can lead to statistically and clinically significant changes across various symptom domains and in patients with a variety of psychiatric diagnoses, and support the implementation of this non-invasive and budget-friendly exercise.FundingNo Funding
Familiarity with Psychiatric Pharmacogenomic Testing in Physicians and Advanced Practice Providers: Educational Opportunities
Authors: Parikh Sagar V. , Albers Renee E. , Maheshwari Priya , Kartikeyan Ramya , Kasten Chelsea R. , Bahra Sukhbir , Lubarda Jovana , Guevara Natalie , Johnson Holly L. , Griggs Ryan B. 
Published: January 2025

IntroductionPharmacogenomic (PGx) testing identifies individual genetic variation that may inform medication treatment. Lack of awareness and education may be barriers to implementing routine PGx testing. To characterize current PGx testing utilization and educational needs we conducted a survey of various provider types.MethodsHealthcare providers in the primary care setting were targeted between November 2022 and February 2023 via the Medscape Members paid market research program. The survey included 5 demographic, 5 multiple-choice, and 4 multi-component five-point Likert scale questions to assess PGx sentiments, use, and education in mental health (e.g., depression) and primary care (e.g., cardiovascular disease) conditions. Responses were descriptively compared.ResultsOf 305 U.S. provider respondents [40% nurse practitioners (NPs), 33% frontline MDs/DOs, 3% physician assistants (PAs), 24% other], most indicated that they “don’t use” (44-49%) or “have never heard of” (19-20%) PGx testing for mental health conditions. The most helpful sources to learn about PGx testing were accredited CE/CME activities (55-61%) and peer-reviewed publications (57-59%). Most NPs/PAs preferred webinars (62%) or online learning portal (57%) formats. MDs/DOs had no preference for webinars or learning portals over conferences, written materials, or academic presentations (45-47%). NPs/PAs were more interested in learning about PGx testing than MDs/DOs (4.29/5 vs. 3.96/5 average score).ConclusionsThese data reveal awareness level and desired learning opportunities for PGx testing between types of healthcare providers. Education should be tailored to meet providers’ preferred learning formats and information sources, such as offering CE/CME through an online learning portal.FundingMyriad Genetics, Inc.
Sustained Improvements in Chorea Associated with Huntington Disease with Once-Daily Valbenazine: Interim Results from a Long-Term Open-Label Study
Authors: Stimming Erin Furr , Claassen Daniel O. , Kayson Elise , Goldstein Jody , Hinton Sean C. , Klepitskaya Olga , Zhang Hui , Liang Grace , Haubenberger Dietrich 
Published: January 2025

IntroductionIn a recently published Phase 3 trial (KINECT™-HD; NCT04102579), once-daily treatment with valbenazine significantly improved chorea versus placebo in adults with Huntington disease (HD). Individuals who completed KINECT-HD, along with de novo participants, were allowed to enroll in KINECT™-HD2 (NCT04400331), the first long-term study of once-daily valbenazine for chorea associated with HD. Pre-planned interim analyses from this ongoing study were conducted to evaluate the maintenance of valbenazine’s effect on chorea and its long-term safety in adults with HD.MethodsAll KINECT-HD2 participants start valbenazine at 40 mg with increases to 60 mg (Week 2) and 80 mg (Week 4); target maintenance dose is 80 mg once daily until end of treatment (up to 156 weeks). Concomitant antipsychotic medications are allowed. Efficacy outcomes, analyzed by study visit, include mean changes from baseline in Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score and response status for Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C). Responders are defined as participants with a score ≤2 (rating of “much improved” or better). Efficacy outcomes up to Week 50 (˜1 year) are reported. Treatment-emergent adverse events (TEAEs) are presented for all participants who received ≥1 dose of study drug, regardless of time in study (2 to 104 weeks). All interim outcomes were analyzed descriptively.ResultsOf 127 participants enrolled at the time of analysis, 98 (77.2%) had completed KINECT-HD and 29 (22.8%) were newly enrolled. Of 125 participants who received treatment, 65 (52.0%) were female and 118 (94.4%) were white; mean age (±SD) was 54.8 (±11.5) years. A mean reduction in TMC score was observed by Week 2 with valbenazine 40 mg (-3.4 [±3.1], n=118); mean reductions were sustained from Week 8 (5.6 [±3.6], n=110) to Week 50 (-5.8 [±4.1], n=66) (all valbenazine doses). At Week 50, 76.9% (50/65) of participants met the pre-defined threshold for CGI-C response; 74.2% (49/66) met the threshold for PGI-C response. Analyses in participants taking concomitant antipsychotic medications are ongoing and will be presented at the meeting. Of the 125 participants who received treatment, 119 (95.2%) reported at least 1 TEAE and 17 (13.6%) discontinued due to a TEAE. The most commonly reported TEAEs were falls (30.4%), fatigue (24.0%), and somnolence (24.0%).ConclusionsInterim TMC data from KINECT-HD2 indicated chorea improvement with once-daily valbenazine by Week 2 (3.4 [±3.1] with 40 mg), similar to KINECT-HD Week 2 results (-2.9 [±3.0]). The interim analyses also indicated that long-term treatment with valbenazine was well tolerated and provided clinically meaningful improvement in chorea severity for up to ˜1 year.FundingNeurocrine Biosciences, Inc.
Correlates of Psychiatric Polypharmacy Among Child and Adolescent Psychiatric Inpatients
Authors: Lynch Sean , Becker Timothy , Shanker Parul , Staudenmaier Paige , Martin Dalton , Leong Alicia , Rice Timothy 
Published: January 2025

BackgroundRates of psychiatric illness among the child and adolescent population have increased over the past several decades. As social and government agencies work to expand access to mental health treatment, more and more children and adolescents are receiving medications for their symptoms. However, many drugs used in this population are not approved for people under the age of 18, and have not been studied in terms of long-term impact on the developing brain. A significant proportion of these patients receive psychiatric polypharmacy, or the prescription of 2 or more psychotropic agents. This rate has increased from about 8% in 1996 to over 40% in 2005. Factors correlated with polypharmacy include older age, male gender, White race, and low socioeconomic status. Polypharmacy can increase the risk of drug-drug interactions, increase morbidity/mortality through cumulative toxicity, and cause decreased medication adherence.Study Aims: This study aimed to examine psychiatric polypharmacy specifically among psychiatrically hospitalized patients in a New York City hospital, and to determine the impact of the COVID-19 pandemic.MethodsThis IRB-approved study reviewed the medical records of 1101 child and adolescent patients that were psychiatrically hospitalized between June 1 2018 and November 30 2021 at Mount Sinai Morningside. Sociodemographic and clinical information was collected and analyzed using SPSS.ResultsIn this sample, 29.4% of patients received psychotropic polypharmacy. The polypharmacy group contained a higher percentage of males, White patients, and fewer Asian/South Asian patients. They had on average more hospitalizations, a longer hospitalization period, and were more likely to be diagnosed with an impulsive/behavioral disorder, developmental disorder, or bipolar spectrum disorder. The polypharmacy group were twice as likely to receive medication for agitation while hospitalized. A regression model identified positive predictors of polypharmacy as having a history of violence and a higher number of psychiatric hospitalizations. Negative predictors included non-White race. White patients had the highest average number of medications and Asian/South Asian patients had the lowest. No impact of the COVID-19 pandemic was found.ConclusionPsychiatric polypharmacy is extremely common in the child and adolescent population that requires psychiatric hospitalization. Increased behavioral needs, such as episodes of violence, as well as greater illness severity, as indicated by greater number of hospitalizations, may be the driving factors behind polypharmacy. Further investigation is indicated to determine other contributing causal factors and to track long-term consequences of psychiatric polypharmacy.FundingNo Funding
Introducing S.C.O.P.E. : Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement An Interactive Digital Platform to Educate on Schizophrenia Care
Authors: Correll Christoph U. , Rubio Jose M. , Citrome Leslie , Kane John M. , Mychaskiw Marko A. , Thompson Stephen , Franzenburg Kelli R. , Suett Mark , Kotak Sameer 
Published: January 2025

IntroductionHealthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating this population.Methods4 experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care.ResultsS.C.O.P.E.™ is a freely-available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. S.C.O.P.E.™ provides HCPs with considerations in common clinical scenarios met in inpatient and outpatient settings, as well as questions to consider when patients present to the emergency department. The potential usefulness of LAIs is explored in each scenario. Clinical education videos prepare nurse practitioners, social workers, and case managers to address patient concerns and communicate the benefits of LAI treatment. S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.ConclusionsS.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia and the role of LAIs in schizophrenia management.FundingTeva Branded Pharmaceutical Products R&D, Inc.
A Thorough QT Study Using C-QTc to Evaluate the Effects of Centanafadine on Cardiac Repolarization
Authors: Shoaf Susan E. , Turkoglu Osman , Wang Xiaofeng , Gordon Jennifer Repella 
Published: January 2025

IntroductionCentanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) in development for treatment of attention-deficit/hyperactivity disorder (ADHD). The effect of CTN on cardiac repolarization from a thorough QT (TQT) trial is reported.MethodsIn this double-blind, placebo (PBO)- and active-controlled, 3-period crossover TQT trial, healthy adults (18-65 years) were randomized to dosing sequences including CTN (800 mg supratherapeutic dose: 4 x 100 mg tablets in the morning and 5 hours later), CTN PBO (4 PBO tablets in the morning and 5 hours later), and active control moxifloxacin (400 mg + CTN PBO in the morning and CTN PBO 5 hours later). Morning doses were separated by 72 hours. Plasma was collected and data were extracted from continuously recorded ECGs for 24 hours following dosing. Effects on ECG parameters (QT interval with Fridericia correction factor [QTcF], PR and QRS intervals, and T- and U-wave morphology), and heart rate (HR) were assessed. The primary analysis was C-QTc, the relationship between drug concentration and PBO-corrected change from baseline in QTcF (ΔΔQTcF). Categorical analyses of ECG parameters were conducted for changes in QTcF, PR, and QRS intervals and in HR.ResultsOf 30 participants enrolled, 56.7% were male and 86.7% were White. Mean (SD) age was 37.6 (14.5) years; mean (SD) BMI was 26.4 (3.4) kg/m2. The slope (90% CI) of the C-QTc relationship for CTN was −0.001 (−0.003, 0.00002) msec/[ng/mL] and not significant. The predicted ΔΔQTcF (90% CI) at the geometric mean Cmax of CTN 800 mg was −2.72 (−6.92, 1.48) msec. A significant slope (90% CI) of the C-QTc relationship for moxifloxacin (0.004 [0.002, 0.006] msec/[ng/mL]) and a predicted ΔΔQTcF (90% CI) at the geometric mean Cmax of moxifloxacin 400 mg above 5 msec (11.75 [8.25, 15.24]) confirmed assay sensitivity. No ΔΔQTcF ≥10 msec was observed for CTN at any postdose time point; all upper limits of 90% CIs of ΔΔQTcF were <10 msec. The by-time-point analysis showed the maximum least squares mean difference in ΔQTcF (90% CI) between CTN and PBO was 1.64 (−1.40, 4.68) msec at 24 hours postdose. No CTN-treated participants had a QTcF increase of >30 msec; no relevant increases in PR or QRS interval or HR were observed. Four participants had >25% decrease in HR and <50 beats per minute. No abnormal U waves were observed; 1 participant had abnormal T-wave morphology. No serious TEAEs or deaths were reported. The most frequently reported TEAEs with CTN were nausea (24.1%), dizziness (24.1%), and decreased appetite (13.8%).ConclusionsIn this TQT trial, centanafadine, a potential first-in-class NDSRI in development for treatment of ADHD, had no clinically meaningful effect on cardiac repolarization and was generally safe and well tolerated.Previous presentation: 2023 ACCP Annual Meeting, September 10–12, 2023, Bellevue, WAFundingOtsuka