bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Viloxazine ER (Qelbree) for ADHD in Adults Based on Prior Stimulant Exposure
Authors: Mattingly Greg , Young Joel , Earnest Jami , Koch Jennifer , Qin Peibing , Rubin Jonathan
Published: January 2025

Introduction

Although many patients respond equally well to both stimulant and nonstimulant medications for ADHD, some patients respond preferentially to one class over another. Currently, most patients receive a stimulant as first-line therapy; however, nonstimulants present fewer obstacles for prescribers and patients and have low abuse/misuse potential. Still, when patients have suboptimal response to stimulants, physicians may be reticent to switch to a nonstimulant medication due to concerns that the nonstimulant response will be less robust or less preferable for patients. Viloxazine ER (viloxazine extended-release capsules; Qelbree®) is a nonstimulant, FDA-approved treatment for ADHD in children (≥6 years) and adults. This post-hoc analysis of adult Phase 3 trial data (NCT04016779) evaluates response to viloxazine ER (200-600 mg/day) based on whether or not patients reported a history of previous stimulant use.

Methods

For patients randomized to viloxazine in this Phase 3, double-blind, placebo-controlled trial, the change from baseline (CFB) in Adult ADHD Investigator Symptom Rating Scale (AISRS) score (primary trial outcome) was analyzed for prior stimulant users vs. nonusers using MMRM. Prior stimulant use was based on patient-reported medication history recorded upon enrollment. Subjects using stimulants at the time of study screening were required to undergo a ≥1-week washout period prior to randomization.

Results

Of 372 patients treated, 189 received viloxazine ER. Of the patients who received viloxazine ER, 40 reported prior stimulant use and 149 did not. Mean (SD) baseline AISRS scores for prior stimulant users and nonusers were 38.5 (7.40) and 38.3 (6.44), respectively. Response appeared similar in both patient groups. At Week 6/End of Study (EOS) the least squares (LS) mean (SE) CFB AISRS scores for prior stimulant users and nonusers were -15.8 (2.51) and -15.6 (1.08)]; treatment difference -0.2 (2.41); P=0.93. Though not significant, prior stimulant users showed a larger magnitude of improvement on the AISRS at early timepoints compared to those without prior stimulant use [Week 1, LS mean (SE) CFB AISRS Total scores: -9.2 (1.40) vs. -6.8 (0.70), respectively; treatment difference: -2.4 (1.56); P=0.12.]

Conclusions

A history of prior stimulant use did not appear to influence the magnitude of ADHD symptom response to viloxazine ER in this preliminary analysis of Phase 3 trial data in adults. Rather, subjects with prior stimulant use showed numerically larger reductions in AISRS scores at early timepoints that were not significantly different from those without prior stimulant use. Additional analysis should be undertaken to evaluate patterns of response in the pediatric population.

Funding

Supernus Pharmaceuticals, Inc.
Viloxazine Extended-Release Capsules in Children and Adolescents with ADHD: Final Results of a Long-Term, Phase 3, Open-Label Extension Study
Authors: Findling Robert L. , Fry Nicholas , Katic Alain , Liebowitz Michael , Maldonado-Cruz Zulane , Qin Peibing , Waxmonsky James G. , Yarullina Ilmiya , Rubin Jonathan
Published: January 2025

Introduction

Viloxazine ER (extended-release capsules; Qelbree®) is a nonstimulant medication, FDA-approved for ADHD in children (≥6 years) and adults. Efficacy and safety for children and adolescents were evaluated in one phase 2 [NCT02633527]and four phase 3 [NCT03247517, NCT03247556, NCT03247530, and NCT03247543], double-blind (DB), placebo-controlled trials that fed into a long-term, open-label extension (OLE) trial [NCT02736656]. Here we report the findings from this OLE trial.

Methods

Participants completing the DB trials were eligible for the OLE. Viloxazine ER was initiated at 100 mg/day (children) or 200 mg/day (adolescents) and adjusted (if needed) over a 12-week Dose-Optimization Period (up to 400 mg/day [children] or 600 mg/day [adolescents]). Maintenance treatment then continued up to 72 months. Safety assessments included adverse events (AEs), clinical laboratory tests, vital signs, ECG (12-lead), and the Columbia Suicide Severity Rating Scale (C-SSRS). Efficacy assessments included the ADHD Rating Scale, 4th (Phase 2) or 5th (Phase 3) Edition (ADHD-RS-IV/5), and the Clinical Global Impression-Improvement (CGI-I) scale. Efficacy was assessed relative to DB baseline at study visits ˜ 3 months apart. Two response measures, 50% improvement in ADHD-RS-IV/5 Total score and CGI-I score of 1-2, were also evaluated.

Results

1100 individuals (646 children; 454 adolescents; 66.5% male/33.5% female) received treatment. Median (range) exposure to viloxazine ER was 260 (1 to 1896) days. AEs were reported by 57.3% participants, most commonly (≥5%) nasopharyngitis (9.7%), somnolence (9.5%), headache (8.9%) decreased appetite (6.0%), and fatigue (5.7%). AEs were mostly mild or moderate in severity (3.9% reported any severe AE); AEs led to viloxazine ER discontinuation for 8.2%. The mean (SD) changes from DB baseline in ADHD-RS IV/5 Total score were -17.0 (14.18) (viloxazine ER) and -11.2 (13.19) (placebo) at the last DB study visit, 24.3 (11.96) at OLE Month 3, and 22.4 (13.62) at participants’ last OLE study visit. ADHD-RS-IV/5 and CGI-I responder rates each exceeded 65% at all OLE visits following Dose-Optimization.

Conclusions

The safety and efficacy of viloxazine ER were maintained with long-term use in children and adolescents with ADHD. No new safety concerns emerged, and efficacy results suggested potential for continued improvement over that seen during DB treatment.

Funding

Supernus Pharmaceuticals, Inc.
Long-term Safety, Tolerability, and Effectiveness of TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), in Patients With Schizophrenia (SHINE)
Authors: Kane John M. , Citrome Leslie , Harary Eran , Tohami Orna , Eshet Roy , Merenlender-Wagner Avia , Sharon Nir , Elgart Anna , Knebel Helena , Davis Glen L. , Mychaskiw Marko A. , Suett Mark , Franzenburg Kelli R. , Correll Christoph U.
Published: January 2025

Introduction

In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.

Methods

Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).

Results

334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.

Conclusions

TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.

Funding

Teva Branded Pharmaceutical Products R&D Inc.

Study Registration Number: NCT03893825
Evaluation of Dermal Irritation with the Dextroamphetamine Transdermal System (d-ATS) in Healthy Adults and Patients with ADHD
Authors: Meeves Suzanne , Komaroff Marina , Haj-Ibrahim Houda , Castelli Mariacristina , Khan Mahwish , Balakrishnan Kanan
Published: January 2025

Background

The d-ATS patch was developed as an alternative to oral amphetamine formulations for attention-deficit hyperactivity disorder (ADHD). The US Food & Drug Administration (FDA) recommends evaluating irritation of transdermal patches under intended (rotating application sites) and exaggerated use (repeated application to one site). These studies assessed irritation after d-ATS application.

Methods

Intended Use: In Study 1, adults with ADHD, d-ATS was applied daily (9-hour application) for 4 weeks rotated between 5 sites (left/right: hip, flank, chest, upper arm, upper back), with irritation assessed on Days 1, 7, 14, 27, and 28. In Study 2, children and adolescents with ADHD, d-ATS was applied daily (9 hours) for 5 weeks to the hip (left or right), with irritation assessed daily.

Exaggerated Use: In Study 3, adults with ADHD, d-ATS was applied daily (9 hours) to the hip (repeated application to one site) for 4 weeks, with irritation assessed daily. In Study 4, healthy adults, 1 d-ATS and 1 placebo patch were applied daily (24 hours) for 21 days to the back (repeated application to 1 site), with irritation assessed daily.

Irritation was assessed by a trained evaluator 30-60 min after patch removal using Berger and Bowman Dermal Response (0-7, with 7 being the worst reaction) and Other Effects (0-3, with 3 being the worst reaction) scores. Dermal Response and Other Effects scores were added together for the combined score. A combined score of ≥3 was considered clinically meaningful irritation.

Results

Intended Use: In Study 1 (N=15), meaningful irritation after patch removal was reported in 9/15 subjects (60%). The mean (SD) combined score was 1.05 (0.21), with no treatment-emergent adverse events at the application site. In Study 2 (N=110), all combined irritation scores were ≤3 for d-ATS, with a combined score of 3 reported by 2% of patients. There were no discontinuations due to dermal reactions in either study.

Exaggerated Use: In Study 3 (N=20), meaningful irritation was reported in 19/20 subjects (95%). The mean (SD) combined score was 1.63 (0.78). In Study 4, mean (SD) combined scores were 2.1 (0.73) for d-ATS and 1.3 (0.69) for placebo (N=206 for both), with no discontinuations due to dermal reactions.

Conclusions

These results support previous findings that d-ATS is safe and well tolerated for ADHD. After intended use, irritation was minimal and did not cause study discontinuations.

Funding

Noven Pharmaceuticals, Inc.
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

Introduction

Esketamine 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.

Methods

This 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.

Results

Case 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.

Conclusions

Severe 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.

Funding

No 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

Introduction

Narcolepsy 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.

Methods

Patients 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.

Results

Twenty-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.

Conclusions

Study 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.

Funding

Alkermes, 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

Background

Schizophrenia 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.

Methods

A 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.

Results

In 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%

Conclusion

This 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.

Funding

Medscape 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

Objectives

To 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.

Methods

Psychiatric 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.

Results

The 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.

Conclusions

The 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.

Funding

No 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

Introduction

Pharmacogenomic (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.

Methods

Healthcare 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.

Results

Of 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).

Conclusions

These 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.

Funding

Myriad Genetics, 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

Background

Rates 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.

Methods

This 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.

Results

In 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.

Conclusion

Psychiatric 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.

Funding

No 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

Introduction

Healthcare 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.

Methods

4 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.

Results

S.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.

Conclusions

S.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.

Funding

Teva 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

Introduction

Centanafadine (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.

Methods

In 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.

Results

Of 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%).

Conclusions

In 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, WA

Funding

Otsuka
Kandinsky Clerambault Syndrome Manifesting as Tinnitus
Authors: Sharma Vasudha , Shaaban Luai , Ali Taseen , Hirsch Alan R
Published: January 2025

Introduction

Tinnitus not heretofore been described as the only manifestation of delusional possession in Kandinsky-Clerambault syndrome. Such a case is presented.

Methods

Case Report: A 70-year-old left handed (pathological) man, eight years prior to presentation, noted gradual onset of decreased hearing and high- pitched constant tinnitus AU made worse with stress. Initially only present in quiet, it intensified, ultimately present in all situations, even with ambient background noise. He believed that the Devil was inside of his head, had been there for many years, and was making his life unbearable by subjecting him to the tinnitus. Other than the tinnitus, the devil did not cause any other symptoms, nor did it communicate with him in any fashion. In an effort to eliminate the Devil-induced tinnitus, he twice attempted suicide through self-strangulation. The tinnitus persisted despite treatment with mirtazapine and lumateperone.

Results

Abnormalities in physical examination: General: Decreased blink frequency. Continuous fidgeting and generalized tremulousness. Neurological examination: Mental status examination: Hypoverbal. Able to remember 5 digits forwards and 3 digits backwards. Unable to remember any of four objects in 3 minutes with and without reinforcement. Presidents as follows: Biden, Obama, ?. Animal Fluency Test: 7 (Abnormal). Cranial Nerve (CN) Examination: CN I Alcohol Sniff Test: 0 (Anosmia). CN VIII Calibrated Finger Rub Auditory Screening Test: Strong 2 AU. Motor Examination: 1+ cogwheel rigidity in the right upper extremity. Gait Examination: Unstable tandem gait. Reflexes: 1+ throughout. Other: Tinnitus Severity Questionnaire : 38/40 (Severe tinnitus). Tinnitus Handicap Inventory: 94/100 (Grade 5-
Catastrophic handicap).

Discussion

While Kandinsky Clerambault Syndrome, Delusion of Possession Syndrome is uncommon in the United States (Dimkov, 2020; Enoch, 2020), 46% of Italians believe in the Devil (Marra, 1990) and 0.6% of Canadians believe that they have been possessed by a demon (Ross & Joshi, 1992). Although the most common neurological presentation of Kandinsky Clerambault syndrome is glossolalia, sensory phenomenon of anosmia (Chand et al, 2000; Medeiros De Bustos et al, 2014), ageusia (Chand et al, 2000), kinaesthesia (Gedevani et al, 2022), allochiria (Medeiros De Bustos et al, 2014), synesthetic neuralgia (Medeiros De Bustos et al, 2014), cenesthesia (Medeiros De Bustos et al, 2014), pain (Medeiros De Bustos et al, 2014) and anaesthesia (Yap, 1960) have also been described. While tinnitus has not been reported with Kandinsky Clerambault, it has been noted to occur with depression, anxiety (Zöger et al, 2006; Salviati et al, 2013), and psychosis (Frankenburg & Hegarty, 1994; Jain et al, 2017). Given the widespread belief in the general population of the Devil and possession by external entities, assessment of presence of Kandinsky Clerambault Syndrome in those with intractable tinnitus may be worthwhile.

Funding

No Funding
Characteristics and Outcomes of Hospitalized Psychiatric Inpatients Treated with Buprenorphine for Co-occurring OUD
Authors: Sacks Ashley , Gordillo Victor , Lynch Sean , Klepacz Lidia , Ferrando Stephen
Published: January 2025

Introduction

Despite being the gold standard for long term treatment and mortality reduction, medications for opioid use disorder (mOUD) are under utilized despite ongoing efforts to reduce barriers to access, with only 18% of qualifying patients undergoing treatment. Approximately 38% of patients nationally with an opioid use disorder (OUD) have a co-occurring psychiatric diagnosis; however, treatment for these co-occurring illnesses frequently do not occur simultaneously, especially among acutely psychiatrically ill patients. Inpatient psychiatric units often do not initiate patients on mOUD, such as buprenorphine, possibly due to lack of national policy encouraging expanded access. This study involves a pilot mOUD consultation service for patients admitted to inpatient psychiatric units, and aimed to characterize the patients involved, and compare certain variables (such as length of stay (LOS)) to inpatients without an OUD.

Methods

This IRB-approved retrospective single-site (level 1 trauma in academic hospital just outside New York City) study examined the medical records of patients who received consultations from our service between January 1st 2018 and August 15th 2020. Demographic and clinical information was collected and analyzed for descriptive statistics. There were no interventions; the primary outcome gathered was average length of stay for patients consulted.

Results

123 patients received consultations during this time period. Patients had an average age of 37 years, identified predominantly as male, and were mostly White. About one third of the population was undomiciled, and almost three quarters were unemployed. Over half of the patients had prior treatment with buprenorphine. The most common primary psychiatric diagnosis was depression (over 50%), followed by bipolar disorders and schizophrenia spectrum illness. About 40% of patients had co-occurring stimulant use, followed by about 30% with marijuana use, and 16% with benzodiazepine use. The average LOS among patients treated with mOUD was not significantly longer than the average LOS for the inpatient units overall. Over half of the patients were established with outpatient or inpatient substance use treatment following discharge from psychiatry.

Conclusions

Our data supports initiating patients with co-occurring OUD and psychiatric illness on mOUD, regardless of severity of acute psychiatric symptoms. Our study did not find that initiating substance use treatment prolonged LOS. Initiating treatment on the psychiatric unit may have increased engagement in outpatient addiction services. Further studies are required to characterize potential benefits.

Funding

No Funding
Diagnostic Challenges of Late-Onset Mania versus Dementia with Behavioral Disturbances: A Case Report
Authors: Zhang Yuxi , Ballone Nina
Published: January 2025

Introduction

Late-onset mania presents as a diagnostic challenge given the interplay between psychiatry and neurology. Neurocognitive disorders, especially the behavioral subtype of Frontotemporal Dementia (FTD), are among one of the differential diagnoses in patients presenting later in life with manic-like symptoms. Here we discuss a case of new-onset manic symptoms in an elderly patient with no prior history of bipolar disorder and conduct a comprehensive literature review to assist with the diagnostic challenges of late-onset mania and dementia with behavioral disturbances.

Case

Mrs. X is a 67-year-old female with bipolar disorder diagnosed 2 months prior to admission who presented to the hospital after a mechanical fall and witnessed seizure-like activity thought to be due to benzodiazepine withdrawal. She was found to have new atrial fibrillation that was stabilized, and clonazepam was resumed. Psychiatry was consulted to assist with manic behaviors. On initial evaluation, Mrs. X presented as anxious, distractible, tangential with pressured speech, increased psychomotor activity, and paranoid towards her husband. She was treated for a urinary tract infection but otherwise workup was unremarkable. Head imaging demonstrated gray matter volume loss that appeared more prominent in the temporal and frontal lobes. Once transferred to the inpatient psychiatry unit, she presented with elevated mood, excessive jocularity, disinhibition, and poor insight. SLUMS of 18 noted poor attention, processing, and short-term recall. She was started on divalproex sodium titrated to 1500 mg daily (VPA level 108 mcg/mL) and olanzapine 25 mg daily. Observations throughout this time included minimal change in affect, elevated mood, memory deficits and social disinhibition. She did have less aggression, minimal paranoia towards her husband and circumstantial thought process although noted with confabulation.

Methods

We completed a comprehensive literature review utilizing PubMed and Google Scholar. Search terms included combinations of “late-onset”, “bipolar disorder”, “mania”, “neurocognitive disorder”, “dementia”, “frontotemporal”, “behavioral disturbances”.

Discussion

Once Mrs. X’s initial delirium resolved, she remained with manic-like symptoms. Collateral, brain imaging of reduced gray matter volume in the frontal and temporal lobes, and lack of response to high doses of a mood stabilizer and antipsychotic favor a probable neurocognitive disorder with behavioral disturbances. Literature reviewed helped to narrow down the differential diagnosis for Mrs. X and allowed for a more comprehensive treatment plan.

Conclusion

Diagnostic elucidation of late-onset mania relies on a comprehensive investigation into psychiatric and non-psychiatric etiologies, a detailed collateral history, and a neuropsychiatric lens. Neurocognitive disorders remain an important differential diagnosis.

Funding

No Funding
Top-Line Results from Phase 3 PALISADE-2 Trial of Fasedienol (PH94B) Nasal Spray in Social Anxiety Disorder (SAD)
Authors: Liebowitz Michael R. , Salmán Ester , Hanover Rita , Reed Brittany , Baker Ross A. , Monti Louis
Published: January 2025

Introduction

Fasedienol (PH94B; 3β-androsta-4,16-dien-3-ol) is a synthetic neuroactive nasal spray from the androstane family of pherines. Intranasal fasedienol activates receptors in peripheral nasal chemosensory neurons connected to subsets of neurons in the olfactory bulbs that in turn are neurally connected to neurons in the limbic amygdala involved in the pathophysiology of SAD and potentially other anxiety and mood disorders. Fasedienol is locally metabolized in the olfactory mucosa without systemic uptake or binding to CNS receptors. The objective of the present study was to compare fasedienol vs. placebo during a public speaking challenge in subjects with SAD.

Methods

This was a multi-center, double-blind, randomized, placebo-controlled study (NCT05011396). After screening (Visit 1), all subjects completed Visit 2 (V2, Baseline, placebo nasal spray administered to all subjects) and participated in a 5-minute public speaking challenge (PSC) during which Subjective Units of Distress Scores (SUDS) were recorded. Subjects with SUDS >= to 70 were invited back a week later for the Visit 3 (V3) treatment visit and randomly allocated to receive either fasedienol (3.2 μg intranasally) or placebo, then undergo a second 5-minute PSC, with SUDS scores recorded. After the V3 PSC, subjects completed a Patient Global Impression of Change (PGI-C) and trained raters completed a Clinical Global Impression of Improvement (CGI-I). CGI-I responders were defined as those assigned scores of 1 (very much improved) or 2 (much improved); PGI-C responders reported scores of 1 (very much less anxious) or 2 (much less anxious). ANCOVA with baseline SUDS as a covariate was used to compare change in mean SUDS from V2 to V3 for the subjects administered fasedienol at V3 vs those who received placebo at V3.

Results

Fasedienol-treated patients (n=70) demonstrated a statistically significant greater change in mean SUDS score (least-squares (LS) mean = -13.8) compared with placebo (n=71, LS mean = -8.0), for a difference between groups of -5.8 (p=0.015). The proportion of CGI-I responders was higher in the fasedienol group 37.7% vs. placebo 21.4% (p=0.033), as was the proportion of PGI-C responders: fasedienol 40.6% vs. placebo 18.6% (p=0.003). Fasedienol was well-tolerated with no treatment-emergent adverse events above 1.5% occurrence.

Conclusion

The Phase 3 PALISADE-2 trial results demonstrated that a single dose of fasedienol prior to a stressful PSC produced efficacy on patient-rated SUDS and PGI-C, as well as the clinician-rated CGI-I. The results also confirmed the nasal-amygdala neural circuits as a new portal for administration of pharmaceuticals. The data support continued development of fasedienol as a first-in-class, rapid-onset, well-tolerated treatment option for SAD without addictive properties.

Funding

Vistagen Therapeutics
A Veteran with PTSD and Bipolar Disorder Type I with Psychotic Features
Authors: Becker Ryan , Billakanti Rohit , Guillermo Chrisalbeth
Published: January 2025

This case discusses a 33-year-old transgender Army Veteran, diagnosed with co-occurring Bipolar Disorder Type 1 (Bipolar I) and Post-Traumatic Stress Disorder (PTSD), both with psychotic features. The patient exhibited recurrent mood swings, delusions, auditory hallucinations, and passive suicidal thoughts. Concurrent symptoms, such as disrupted sleep, irritability, and intrusive thoughts, complicated diagnosis and treatment. The patient’s medical history included migraines, chronic pain, medication-induced seizures, traumatic brain injury (TBI), and Borderline Personality Disorder.

During the assessment, the patient displayed mood fluctuations, cognitive issues, and intermittent tearfulness. They were averse to sedative medications and preferred non-pharmacological approaches. The Alpha-Stim (Cranial Electrical Stimulator – CES) was recommended for anxiety, depression, insomnia, and chronic pain.

Medication options (Aripiprazole, Lurasidone, and Risperidone) were discussed, and the patient chose Aripiprazole. The treatment plan included Dialectical Behavior Therapy for Borderline Personality Disorder and potential polysomnography to evaluate sleep disorders.

This case underscores the management challenges of co-occurring Bipolar I and PTSD with psychotic features, emphasizing the need for further research on their interplay, impact on functioning, and optimal treatments. It also explores CES as a potential intervention for psychosis during mood episodes.

Funding

No Funding
Service evaluation of ‘GP at Door’ of accident and emergency services in Eastern England
Authors: Brainard Julii , Rice Aiden , Hughes Gareth , Everden Paul
Published: January 2025

Aim:

We describe activity, outcomes, and benefits after streaming low urgency attenders to General practice services at Door of Accident and Emergency departments (GDAE).

Background:

Many attendances to A&Es are for non-urgent health problems that could be better met by primary care rather than urgent care clinicians. It is valuable to monitor service activity, outcomes, service user demographics, and potential benefits when primary care is co-located with A&E departments.

Methods:

As a service evaluation, we describe and analyse GDAE users, reasons for presentation, wait times, outcomes, and co-located A&E wait times at two hospitals in eastern England. Distributions of outcomes, wait times, reasons for attendance, deprivation, and age groups were compared for GDAE and usual A&E attenders at each site using Pearson chi-square tests and accelerated time failure modelling. Performance in a four-hour key performance indicator was descriptively compared for co-located and similar emergency departments.

Findings:

Each GDAE saw about 1025 patients per month. Wait times for usual accident and emergency (A&E) care are relatively short at only one site. Reattendances were common (about 11% of unique patients), 75% of GDAE attenders were seen within 1 hour of arrival, 7% of patients initially allocated to GDAE were referred back to A&E for further investigations, and 59% of GDAE patients were treated and discharged with no further treatment or referral required. Pain, injury, infection, or feeling generally unwell each comprised > 10% of primary reasons for attendance. At James Paget University Hospital, 4.3%, and at Queen Elizabeth Hospital, 16.1% of GDAE attendances led to referral to specialist health services. GDAE attenders were younger and more socially deprived than attenders to co-located A&Es. Patients were seen quickly at both GDAE sites, but there were differences in counts of specialist referrals and wait times. Process evaluation could illuminate reasons for differences between study sites.
Constitutional ImagiNations: on the Imaginal Foundations of the Indian Constitution
Authors: Suresh Sabarish
Published: January 2025

Even after seven decades since it came into force, examinations of the Indian Constitution remain partial and incomplete. It is not widely known that the original ratified copy of the Constitution also makes a visual argument through the opening pages of every part. These elaborately crafted artworks, which are entirely negated in Indian scholarship, are structured in the form of a teleological and linear narrative, encompassing a claim of an unbroken link to an immemorial civilisation. Based on archival research and a hermeneutic that combines imaginal analysis, literary theory, historical scholarship and constitutional jurisprudence, this article will demonstrate that these constitutive images are the aesthetic foundation that imaginally binds the constitutional subject and the collective citizenry, and this article will show how its negation is closely tied to a foundational ambivalence that endures in constitutional law.
Poetics and Performance: Fanfa Bands and the Semiotic Landscape in Northern Haiti
Authors: Yarrington Jonna
Published: January 2025

This paper examines the poetics and cultural significance of fanfa youth band performances in the rural commune of Limonade in northern Haiti. Drawing on observations during fieldwork in 2010 and 2016, it analyzes how fanfa bands, directed by maestros, create complex sign systems through music, movement, and materialities. Utilizing Roman Jakobson’s semiotic theory and Linda Waugh’s expansion of poetic function, the study explores the interpretive relations between these components and their role in constituting a unique cultural soundscape. By examining the selection and combination of musical pieces, routes, and accompanying elements, the research highlights the dynamic interaction between fanfa bands and their social environment. This semiotic analysis offers insights into the broader implications of cultural landscapes and the poetics of performance in Haiti.