bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential seed dispersal agents of Monoon liukiuense on Iriomote Island, Japan
Authors: Furumoto Ryo
Published: April 2023

Monoon liukiuense (Annonaceae) is an endangered tree species distributed in Iriomote Island and Hateruma Island in the Ryukyu (Nansei) Islands, Japan, and in Orchid Island (Lanyu) in Taiwan. While its habitat is confined to small areas surrounded by human-altered landscapes, the matured trees bear abundant fruits, and many offspring grow under the mother trees. M. liukiuense is hypothesised to have lost effective seed dispersers. To test this hypothesis, fate of its seeds and the behaviour of frugivores were observed using time-lapse photography during three fruiting seasons from June 2015 to August 2016 in Iriomote Island, Japan. Although several animal taxa were observed to consume the fruit pulp, only two volant animals, namely the Yaeyama flying fox and large-billed crow, were proposed as seed dispersal agents for M. liukiuense. The present study shows that an average of 82% of the fruits in the canopies fell directly beneath the fruiting trees and an average of 90% of the seeds on the forest floor remained in their original positions. These results suggest that M. liukiuense has lost most of its seed dispersal agents and the chance to expand its distribution.
Welfare, Abortion, and Organ Donation: A Reply to the Restrictivist
Authors: Carroll Emily , Crutchfield Parker
Published: April 2023

We argued in a recent issue of this journal that if abortion is restricted,1 then there are parallel obligations for parents to donate body parts to their children. The strength of this obligation to donate is proportional to the strength of the abortion restrictions. If abortion is never permissible, then a parent must always donate any organ if they are a match. If abortion is sometimes permissible and sometimes not, then organ donation is sometimes obligatory and sometimes not. Our argument was based on the following ideas: (a) that a fetus has full moral status, (b) that parents have special obligations to their offspring, fetus or not, and (c) that this special obligation is to protect them. The result is the conclusion that abortion restrictivists cannot also consistently deny that organ donation should be compulsory.
Aripiprazole: Examining the Clinical Implications of D2 Affinity
Authors: Anam Adiba , Lynch Sean , Mosharraf Nafiz , Soukas Chloe , Gekhman Dmitriy
Published: April 2023

Background

Aripiprazole has high binding affinity for the dopamine D2 receptor, which is thought to be responsible for the antipsychotic effect, though aripiprazole is not the most potent of the second-generation antipsychotics. Theoretically, aripiprazole could displace or outcompete more potent antipsychotics, prompting decreased antipsychotic effect. We describe a case of aripiprazole potentially worsening psychiatric symptoms by blocking paliperidone.

Case

Ms. A is a 43-year-old woman with schizophrenia, multiple inpatient hospitalizations, and a history of court-ordered treatment. She historically has had good response to oral and long-acting formulations of risperidone and paliperidone. Ms. A requested a medication change and was transitioned to aripiprazole lauroxil injection with plan for bimonthly administration. Approximately 1 month after receiving her aripiprazole lauroxil injection, Ms. A presented to our CPEP due to symptoms of psychosis and was admitted to our inpatient unit. She was restarted on oral paliperidone, titrated up to her previously effective dose, and was transitioned to paliperidone palmitate LAI. In contrast to prior admissions, she did not respond well to paliperidone and displayed continued and worsened psychosis.

Discussion

Prior studies have examined how adding aripiprazole to another, more potent D2 antagonist can cause a relapse in psychotic symptoms; however, few studies have investigated the inverse relationship or mechanism. Those that have proposed mechanisms typically refer to aripiprazole’s partial agonist activity as the causative factor, rather than an impediment to antipsychotic binding which we have described. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of aripiprazole to avoid this phenomenon.

Funding

No Funding
Conducting Women’s Groups in the Inpatient Unit: Empowering a High-Risk Population by Preventing Unplanned Pregnancies
Authors: Puri Avanti , Iruvanti Sirisha , Abrudan Patricia , Wargo Samantha , Huebschmann Anna
Published: April 2023

Introduction

Women with mental illness are 5x more likely to experience an unplanned pregnancy due to lower rates of effective contraception use; they also experience higher rates of adverse pregnancy outcomes. Education about women’s reproductive health and family planning are not routinely offered in inpatient mental health and addiction treatment settings.

Methods

Weekly women’s groups on the inpatient psychiatry unit were led by psychiatry residents who were trained and provided a script. Groups focused on structured contraception education followed by an open-discussion format.

Data collected included the percentage of women with history of contraception use, child protective service involvement, unplanned pregnancies, abortions, and percentage of women who found the group helpful. Special care was taken to discuss contraception as a tool for empowering women to make their own decisions about their contraceptive needs.

Results

Thirteen sessions were conducted, and attendance among women on the inpatient unit was 42%. Out of the 32 patients who participated, 100% found the group beneficial and responded they would share information they learned with women outside the group. 26.4% self-identified as using contraception, 50% had unplanned pregnancy, 23.6% have had an abortion, and 26.4% have had child protective services involvement.

Dissemination of contraceptive information in these women’s groups effectively led women to consider options that were available to them and seek contraceptive methods that were appropriate to their situation. Women reported they gained a better understanding of the medical, emotional, and financial implications of unplanned pregnancies. The groups were conducted in an open-discussion format that allowed women to participate in shared experiences; in many cases, the discussions were therapeutic. Feedback from patients and unit staff was positive. Many patients requested further groups to discuss issues women face, such as domestic violence and experiences as a mother.

Conclusions

Conducting women’s groups on the inpatient unit is critical in view of the poor access to healthcare that vulnerable women who seek inpatient psychiatric care experience. The groups on the inpatient unit are unique because it is often the only time these women have an opportunity for crucial, gender-specific preventative healthcare. These groups should further lead to appropriate referral and follow-up with primary care or women’s clinic providers.

Ongoing efforts will be put forth to increase group attendance, to incorporate participation from unit staff, and to build this group into a resident curriculum for group therapy.

Funding

No Funding
Reliability of the Clinician’s Tardive Inventory (CTI)
Authors: Trosch Richard M. , Comella Cynthia L. , Caroff Stanley N. , Ondo William G. , Shillington Alicia C. , LaChappelle Brandon J. , Hauser Robert A. , Correll Christof U. , Friedman Joseph H.
Published: April 2023

Objectives

Currently utilized clinician-rated symptom scales for tardive dyskinesia (TD) have not kept up with the expanding spectrum of TD phenomenology. The objective of this study was to develop and test the reliability of a new instrument, the CTI.

Methods

A movement disorder neurologist devised the outline of the scale. A steering committee (four neurologists and two psychiatrists) provided revisions until consensus was reached. The resulting instrument assesses frequency of abnormal movements of the eye/eyelid/face, tongue/mouth, jaw, limb/trunk, complex movements (e.g., handwringing, self-caressing), and vocalizations. The CTI rates symptoms from 0–3 with 0 = absent, 1 = infrequent/intermittent or only present with activating maneuvers, 2 = frequent intermittent, brief periods without movements, 3 = constant or nearly constant. Functional impairments including activities of daily living (ADL), social impairment, symptom bother, and harm are rated 0–3 with 0 = patient is unaware or unaffected, 1 = symptoms mildly impact patient, 2 = symptoms moderately impact patient, 3 = symptoms severely impact patient. Following institutional review board approval, the CTI underwent inter-rater and test-retest reliability testing. Videos of patient TD examinations were obtained and reviewed by two movement disorder specialists to confirm the diagnosis of TD by consensus and the adequacy to demonstrate a TD-consistent movement. Vignettes were created to include patients’ symptom descriptions and functional, social, or occupational impairments/limitations. Four clinicians rated each video/vignette. Selected videos/vignettes were also subject to an intra-rater retest. Interrater agreement was analyzed via 2-way random-effects interclass correlation (ICC) and test-retest agreement assessment utilizing Kendall’s tau-b.

Results

45 video/vignettes were assessed for interrater reliability, and 16 for test-retest reliability. ICCs for movement frequency were as follows: abnormal eye movement .89; abnormal tongue/mouth movement .91; abnormal jaw movement .89; abnormal limb movement .76; complex movement .87; abnormal vocalization .77; and functional impairments including harm .82; social embarrassment .88; ADLs .83; and symptom bother .92. Retests were conducted on mean (SD) 15 (3) days later with scores ranging from .66–.87.

Conclusions

The CTI is a new instrument with good reliability in assessing TD symptoms and functional impacts. Future validation study is warranted.

Funding

Neurocrine Biosciences
Mental Health Issues for Frontline Hospital Staff During Height of Covid Pandemic 2020
Authors: Gross Diego Garces , Kaplan Yonatan , Talis Geoffrey , Kennedy Cheryl A.
Published: April 2023

Introduction

When the SARS-Cov2 virus hit the New York and New Jersey metropolitan area in Spring 2020, hospitals and hospital workers were hit hard with a new unknown pathogen that either killed people or made them very ill. There were large numbers of severely ill patients that strained resources. Hospital workers had extraordinary stress with multiple additional patients, the need to use personal protective equipment (PPE) in short supply, and faced with a pathogen that had no treatments beyond care and support initially.

Methods

We surveyed our hospital workers in late Spring 2020 to identify the main stressors and find out what measures were helpful. An online anonymous survey included questionnaires about sleep, mood, outside stressors, helpful measures, and how they coped generally. All levels of hospital workers were surveyed. Resources were provided to all respondents.

Results

Over 240 individuals responded to the survey; most respondents were women (76%). ‘Workplace stressors’ topped the chart for 98 of our respondents. The worst workplace stressor that was cited was ‘irritable workforce,’ but ‘lack of ‘protocols’ and ‘shortage of PPE’ were also cited as stressors. ‘Other’ (not described) and ‘taking care of an ill relative’ were rated highly. Those who had ‘symptoms everyday:’ Anhedonia (loss of pleasure or interest), 13%; feeling down and hopeless, 12%; sleep disturbance, 41%; low energy, feeling tired, 29%; appetite disturbance, 26%; poor concentration and attention, 15%. Respondents told us what resources they used and what was most helpful; exercise was most frequently cited as helpful.

Lessons Learned and Discussion

Various resources for formal and informal mental health support were provided to all respondents at the time of survey. Our hospital mounted its own response with support services, as did our medical school and university. A "warm line" was available through the Department of Psychiatry from late March 2020; tip sheets and online groups were widely circulated; State Department of Health provided resources. There were formal peer support sessions and workers helped each other. Medical students provided child care, shopping, and transport. We learned that extra support for workers and more frequent rest and recharge time are important. A weekly "town hall" was instituted and a weekly update about the hospital and support in healthy activities are widely circulated to employees. Those with active PTSD (some were very disturbed by the number of deceased patients) were referred to professional providers. Hospitals need to be ready to deal with epidemics and pandemics more effectively in order to mitigate stress and support workers. Being prepared, not just with equipment, but with protocols in how to proceed should another pandemic come. We learned that listening to workers is important. Workers also need to know how valued they are.

Funding

Department of Psychiatry, New Jersey Medical School
Review of the TAAR1 Agonist Ulotaront: Part I—From Discovery to Clinic
Authors: Hopkins Seth C. , Dedic Nina , Zeni Courtney , Synan Colleen , Koblan Kenneth S.
Published: April 2023

Introduction

Trace amine-associated receptors (TAARs) are a family of G-protein-coupled receptors (GPCRs) first identified in 2001. TAAR1 has emerged as a promising therapeutic target due to its ability to modulate monoaminergic and glutamatergic neurotransmission. Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity that has received FDA Breakthrough Therapy Designation for the treatment of schizophrenia. Here we provide a brief review of the discovery of ulotaront and preclinical research suggesting efficacy in schizophrenia, leading to the first clinical trial of ulotaront resulting in FDA Breakthrough Therapy Designation.

Methods

Ulotaront was discovered through a target-agnostic approach optimized to identify drug candidates that demonstrate an antipsychotic-like profile in vivo but lack D2 and 5-HT2A receptor antagonism. Ulotaront was further characterized by in vitro pharmacology, electrophysiology, behavioral, and imaging studies.

Results

Ulotaront demonstrated an antipsychotic-like profile in a high-throughput, phenotypic behavior screening platform, as well as efficacy in preclinical models of schizophrenia, including phencyclidine (PCP)-induced hyperactivity, prepulse inhibition of acoustic startle, and subchronic PCP-induced deficits in social interaction. Although not fully elucidated, ulotaront’s mechanism of action appears to be mediated by agonism at trace amine-associated 1 (TAAR1) and 5-HT1A receptors. This was further corroborated with whole cell patch clamp recordings, demonstrating inhibition of dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) neuronal firing via 5-HT1A and TAAR1 receptors. Furthermore, ulotaront attenuated the ketamine-induced increase in striatal dopamine synthesis capacity, suggesting that it may modulate presynaptic dopamine dysfunction which is hypothesized to contribute to the pathophysiology of schizophrenia.

Conclusions

Preclinical studies have identified ulotaront as a TAAR1 agonist with antipsychotic-like activity. Ulotaront’s unique receptor profile led to its designation as a member of the new “-taront” class of TAAR1 agonists, distinct in pharmacology from the D2/5-HT2A class of antipsychotics. A companion poster will summarize the efficacy and safety of ulotaront based on initial clinical trials in schizophrenia.

Funding

Sunovion Pharmaceuticals, Inc., and Otsuka Pharmaceutical Development & Commercialization, Inc.
Psychiatric Inpatient Healthcare Resource Utilization and Treatment Patterns Among Patients With Predominant Negative Symptoms in Schizophrenia
Authors: Patel Rashmi , Mehta Darshan , Kadakia Aditi , Won Yida , Dembek Carole , Williams Gwilym , Huang Xueyan , Zeni Courtney , Pikalov Andrei
Published: April 2023

Introduction

Currently approved treatments for schizophrenia (antipsychotics) have demonstrated effectiveness for treating positive symptoms; however, these agents are largely ineffective in treating other domains. Negative symptoms, including avolition, alogia, blunted affect, and asociality, are difficult to treat, and often persist despite adequate control of positive symptoms. Additionally, some patients experience “predominant” (moderate-to-severe negative symptoms that have greater relative severity than co-occurring positive symptoms) or “prominent” (severity of negative symptoms [moderate-to-severe] without any reference to positive symptoms) negative symptoms. These symptoms are known to have great impact on patient social functioning and quality of life, and are associated with poorer clinical course and outcomes for patients. Here, we examined inpatient healthcare resource utilization in patients with schizophrenia experiencing predominantly negative symptoms (PNS).

Methods

De-identified data were extracted from electronic health records in the NeuroBlu Database across 25 US mental healthcare providers. Positive and negative symptom data were derived from free-text records using natural language processing. PNS was defined as the presence of three or more negative symptoms and three or fewer positive symptoms at first clinical contact following schizophrenia diagnosis. Groups were balanced for baseline demographic and clinical characteristics by minimizing the generalized Mahalanobis distance and compared using chi-square and t-tests. Treatment patterns were visualized using Sankey diagrams.

Results

A total of 4444 patients with schizophrenia were identified and 8% were classified as PNS. A balanced cohort of 720 patients (50% PNS) was generated. Patients with PNS were more likely to be hospitalized in the 12 months following diagnosis (PNS: 76%, non-PNS: 60%, χ2: 22.5, p < 0.001) and were switched to a second-line antipsychotic after a shorter first-line treatment duration. The most frequently prescribed antipsychotics differed between groups (PNS: risperidone, aripiprazole, haloperidol; non-PNS: risperidone, olanzapine, other atypical).

Discussion

This study demonstrates that negative symptoms in schizophrenia may be associated with worse illness course and higher healthcare resource utilization. There remains a need for new treatment options for patients with persistent, prominent, or predominant negative symptoms which specifically improve this historically hard-to-treat and assess symptom domain.

Funding

Sunovion Pharmaceuticals, Inc.
Too Sweet to Eat: Delusional Hypergeusia
Authors: Kalita S. , Birwatkar D. , Sundar A. , Hirsch A.R
Published: April 2023

Introduction

Delusional hypergeusia has not heretofore been reported.

Methods: Case report

A 62-year-old right-handed woman described a plethora of complaints after exposure to a solvent aroma, including headaches, diffuse weakness, fatigue, hallucinated smells and tastes, burning mouth syndrome, and panic attacks. The apogee of her symptoms was that salty taste was 800% of normal, making food taste disgustingly salty. She was unable to tolerate potato chips, pizza, spaghetti sauce, Coca Cola, root beer, Sprite, 7 Up, and even bottled water. Sugar was also too sweet, 600% of normal. Foods which were unbearably sweet included cookies, sugar, and breakfast cereals. Sour and bitter were normal.

Results

Abnormalities in Neurological Examination: Mental Status Examination: hyperverbal, loud, overly inclusive, irritable with pressured speech; disheveled, racing thoughts, and tangential. Motor Examination: Drift Test: right pronator drift with right abductor digiti mini sign. Gait Examination: heel walking with bilateral decreased arm swing. Reflexes: bilateral quadriceps femoris 3+, positive left (L) Hoffman’s reflex. Chemosensory Testing: Olfaction: Brief Smell Identification Test: 12 (normosmia). Retronasal Olfactory Testing: Retronasal Smell Index: 1 (Anosmia). Gustatory Testing: Propylthiouracil Disc Taste Test: 10 (normogeusia). Waterless Empirical Taste Test: sweet: 4, sour: 3, salty: 7, bitter: 5, brothy: 0, total: 30 (ageusia to umami, otherwise normogeusia). Neuropsychiatric Testing: Go-No-Go Test: 2/6 (abnormal).

Discussion

Perhaps hypergeusia may not have been true hypergeusia but a misperception of retronasal smell associated hyperosmia with physiologic synesthesia manifested as taste. Peradventure, the perceived hypergeusia, is just one component of a generalized delusional paradigm, where many sensory perceptions are intensified. The perceived delusional hyperosmia may be intensification of the sensory misperception due to an underlying dysgeusia. This may represent a variant of the two-factor hypothesis of delusions whereby a distorted sensory perception is then misrepresented in a delusion. Dysfunction of the right hemisphere, which normally acts to censor the left, allows the delusion to manifest. While two different anatomical abnormalities (one left and one right hemisphere) have been postulated to be the foundation of such delusions, it is distinctly possible that a single lesion of the inferior parietal lobule may be sufficient for both sensory distortions to be produced as well as loss of inhibition of delusional interpretation of distorted sensation of the frontal lobe by the right parietal lobe, yclept the sensorialist hypothesis. In those who present with hypergeusia, search for delusional origin is warranted and in those who present with delusions, query as to perceived hypergeusia may be revealing.

Funding

No Funding
Excessive Daytime Sleepiness in a Real-World Study of Participants With OSA With or Without Comorbid Depression
Authors: Parthasarathy Sairam , Zhang Jerry , Hyman Danielle , Doherty James , Saad Ragy , Fox Benjamin , Marshall Nell J. , Parks Gregory
Published: April 2023

Background

Obstructive sleep apnea (OSA) is a sleep disorder that is highly comorbid with psychiatric disorders, including depression and anxiety. Excessive daytime sleepiness (EDS) is common in psychiatric disorders and OSA. In participants with OSA, EDS can persist despite use of positive airway pressure (PAP) therapy. This analysis of real-world data aimed to describe EDS and its relationship with PAP use in participants with and without depression.

Methods

US residents (≥18 years of age, self-reported physician diagnosis of OSA [from 1/1/2015 to 3/31/2020]) completed a survey in Evidation Health’s Achievement app assessing subjective levels of sleepiness (Epworth Sleepiness Scale [ESS]) and self-reported PAP usage, categorized as nonuse (no PAP use), nonadherent (<4 h/night or <5 d/wk), intermediate (4-6 h/night, ≥5 d/wk), or highly adherent (≥6 h/night, ≥5 d/wk). ESS score >10 defined EDS. A linear model assessed relationships between PAP use and ESS score. P-values are uncontrolled for multiplicity (nominal).

Results

In total, 2289 participants (EDS, n=972; no EDS, n=1317) completed the survey (50.3% female; 82.5% White; mean±standard deviation [SD] age, 44.8 ± 11.1 years). Anxiety and depression were the most common comorbidities and were more common in participants with EDS (49% and 49%, respectively) than those without EDS (41% and 37%, respectively). Overall, EDS was more common among participants with comorbid depression (49%) than those without (38%), even among highly adherent PAP users (46% vs 30%, respectively). In a linear model (PAP users only), an additional 1 h/night of PAP use was associated with lower ESS scores in the subgroup of participants without depression (n=928; estimate [SE], −0.42 [0.09]; P<0.05), but not in the subgroup with depression (n=661; estimate [SE], −0.15 [0.10]; P>0.05). In a sensitivity analysis that excluded participants using medications that cause sleepiness, PAP use was associated with lower ESS scores regardless of depression status; however, EDS remained more common in participants with comorbid depression (46%) than in those without (36%).

Conclusions

In this real-world population of participants with OSA, those with EDS were more likely to have comorbid anxiety or depression. EDS was more common in participants with comorbid depression than those without, even with highly adherent PAP use. PAP use was associated with lower ESS scores in participants without comorbid depression, but not in those with comorbid depression; the use of medications that cause sleepiness may contribute to but does not fully explain this phenomenon.

Funding

Axsome Therapeutics and Jazz Pharmaceuticals
Opioid-Induced Doctor Dolittle Phenomenon
Authors: Hirsch Jack William
Published: April 2023

Background

The Doctor Dolittle delusion, of animals conversing with the sufferer, has not heretofore been reported to occur with heroin intoxication.

Methods

This 23-year-old right-handed single male used heroin daily since the age of 19. For 2 years prior to presentation, 1 hour after injecting at least one bag of heroin IV, he developed hallucinations of animals talking to him. The voices would occur simultaneously with moving their mouths. Dogs would bark, cats would meow, and birds would squawk his name. Insects would engage him in friendly conversation. Different pitches of voice were produced from each animal; birds were high-pitched; squirrels, insects, and cats were lower-pitched; dogs were medium-pitched. As his intoxication resolved, the hallucinations also evaporated.

Results

Mental Status Examination: Oriented x 1, able to recall five digits forwards and three digits backwards. Able to remember none of four objects in 3 minutes without reinforcement and three with reinforcement. Able to spell the word “world” forwards but not backwards.

Discussion

The hallucination of animals talking, coincident with their mouths moving, articulating the words, associated with intoxication with high doses of heroin, with resolution with elimination of heroin, suggests opioid intoxication is the causative factor. The mechanism of zoopsia in Parkinson’s disease has been attributed to dysfunction of the inferior longitudinal and inferior fronto-occipital fasciculi which relay visual information from the occipital cortex to the temporal and the orbitofrontal cortices. Heroin may have induced cortical inhibition, disinhibiting such pathways and thus facilitating these hallucinations. The simultaneous congruent auditory and visual hallucinations suggests a central origin of these, controlling both the auditory and visual system, such as the left superior and middle temporal gyrus, or possibly the cerebellar vermis. What is unique about the current description is that multiple animal and insect species were involved, and that the pitch of their voice was species specific (high-pitched in birds, and low-pitched in rodents and insects). The pitch may reflect the individual’s personal hedonics towards the type of animal or the individual’s interpretations of mass media’s representation of these animals (i.e., cartoons of Looney Toons high-pitched Tweety Bird or Disney’s low-pitched Jiminy Cricket). While it is possibly due to the opioids themselves, heroin is frequently adulterated with fillers which may contain hallucinogenic properties, any of which may have been the pathogenic factor. Autophobia, or the need for social contact, may be the nidus motivating such communicative anthropomorphism. Query as to the presence of such Doctor Dolittle hallucinations in those with heroin or other intoxicants may be revealing.

Funding

No Funding
Electroconvulsive Therapy in Thrombocytopenic Patients: A Case Report and Literature Review
Authors: Nearine Jake , Ongchuan Samantha
Published: April 2023

Introduction

Electroconvulsive therapy (ECT) continues to be one of the most effective treatments for severe and treatment-resistant major depression. Although there are no absolute contraindications to performing ECT, the risks and benefits need to be assessed in all patients. We present a patient with a history of paroxysmal nocturnal hemoglobinuria (PNH) with significant thrombocytopenia, who completed an index course of six ECT sessions without complication. Currently, there are only two published case reports which describe the use of ECT in patients with thrombocytopenia.

Methods

AD is a 37-year-old female with a history significant for MDD, GAD, panic disorder, PNH, and Budd Chiari, who presented to ED for suicidal ideation. Initial labs showed pancytopenia (Hb 4.56 mg/dl, Absolute Neutrophil 0.7 x 103/mL). Given her history of multiple failed SSRIs, ECT was proposed to treat her depression. Anesthesia delayed her initial pre-operative assessment due to concerns regarding her platelet count and risk of bleeding. They recommended transfusion with a preprocedural platelet count goal of 50 x 103/mL. Psychiatry recommended a platelet goal of 20 x 103/mL given previous ECT literature. Patient underwent six ECT sessions without complications. Her platelets ranged from 24–40 x 103/mL and she did not require preprocedural platelet transfusion.

Results

Due to a lack of published literature, there are no formal guidelines for performing ECT in thrombocytopenic patients. The first case report details a 64-year-old female who underwent 12 ECT sessions without complication, while her platelet count ranged from 7–38 x 103/mL. The most recent case report describes a 74-year-old male who underwent nine ECT treatments without complications. The authors decided to transfuse prophylactically if pre-procedure platelet count was less than 20 x 103/mL. The patient underwent nine treatments, requiring eight transfusions. CT head did not show any signs of hemorrhage or structural changes. The authors remarked it is unclear whether the transfusions were necessary.

Conclusions

Even though ECT has been in use for over 80 years, there is still much that is unknown about this treatment modality. This case highlights the lack of absolute contraindications to performing ECT. However, the lack of literature and studies regarding platelet goals in thrombocytopenic patients for ECT delayed patient care in this specific case. We add a third case report in a thrombocytopenic patient who underwent ECT without complications with a pre-procedure transfusion criterion if platelet count was less than 20 x 103/mL. More research needs to be conducted to determine risk and cut-off limits for platelet transfusion prior to performing ECT in thrombocytopenic patients.

Funding

No funding
Optimization of Sleep classification in Patients With Serious Mental Illness Using Accelerometer and ECG Data From a Wearable Patch
Authors: Cochran Jeffrey M.
Published: April 2023

Introduction

Sleep is an important behavioral biomarker for patients with serious mental illness (SMI). The ability to accurately quantify sleep in a real-world setting could thus provide insight into patient well-being. In this study, patients in a sleep lab wore a patch that is part of a digital medicine system (aripiprazole with sensor (AS)) designed to provide objective records of medication ingestion. The patch provided accelerometer and electrocardiogram (ECG) data; polysomnography (PSG) data was collected to be used as the gold standard for sleep stage classification. The accelerometer and ECG data were used to build machine learning classification models to distinguish periods of wake from periods of sleep. To optimize these models for a real-world environment, different data sampling paradigms and methodologies were explored, and resultant model performances were analyzed.

Methods

Data was collected for a total of 220 nights, across 73 unique subjects—42 subjects had a diagnosed SMI (schizophrenia, bipolar disorder I, or major depressive disorder) and 31 subjects were healthy volunteers. PSG data, which provides a sleep stage designation at 30-second intervals, was combined into 5-minute windows, labeled as either “Sleep” or “Wake” based on which class comprised the majority of the 30-second intervals within the window. Accelerometer and ECG features were derived for each 5-minute window. Models were trained with three learning methodologies: a light gradient boosting machine (LGBM), a conditional random field (CRF), and a long short-term memory (LSTM) network. Model performance was tested with the full complement of accelerometer and ECG data, as well as down-sampled subsets of data. Additionally, ECG data from the PSG system was incorporated to test the effect of other ECG sampling strategies.

Results

CRF models produced the best classification performance (AUC = 0.91) with the full patch dataset. Down-sampling to include less than half of the accelerometer data did begin to degrade the specificity of the model. Down-sampling to include less frequent ECG collection did not have a significant effect on model performance; however, changing the sampling paradigm to continuous ECG collection from a block sampling paradigm did lead to more robust classification of when a patient was awake.

Conclusions

Accurately recording sleep in a logistically simple way can provide insights into the well-being of SMI patients. Combining these insights with the objective medication ingestion records provided by AS would be of great value to SMI patients, as well as their caregivers and physicians. This research explores what amount of sensor data is required to accurately quantify sleep and some of the machine learning strategies that can ameliorate data limitations, providing guidance for the optimization of digital device design.

Funding

Otsuka Pharmaceutical Development & Commercialization, Inc.
Lumateperone in Pooled Late-Phase Schizophrenia Trials: Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed
Authors: Citrome Leslie , Durgam Suresh , Edwards John B , Davis Robert E
Published: April 2023

Background

Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder as monotherapy and as adjunctive therapy with lithium or valproate. This post hoc analysis investigated the efficacy and tolerability of lumateperone in patients with schizophrenia via number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Methods

Data were pooled from three late-phase 4–6 week placebo-controlled studies of lumateperone 42 mg/day in adults with schizophrenia and an acute exacerbation of psychosis (Study 005 [NCT01499563], Study 301 [NCT02282761], Study 302 [NCT02469155]). NNT and NNH were calculated vs placebo for several different Positive and Negative Syndrome Scale [PANSS] Total score response cutoffs (percent reduction from baseline) and for adverse events (AEs), respectively.

Results

In the two informative studies (placebo, n=221; lumateperone, n=224), the NNT vs placebo for lumateperone was statistically significant for PANSS Total score reductions from baseline to 4 weeks/endpoint of ≥20% (NNT=9, 95% confidence interval [CI] 5–36) and ≥30% (NNT=8; 95%CI 5–21). In all studies pooled (placebo, n=412; lumateperone, n=406), study discontinuations due to AEs were uncommon and the NNH (389) was not statistically significant from placebo. The only AE with NNH vs placebo <10 was somnolence/sedation (NNH=8; 95%CI 6–12). With lumateperone treatment, weight gain ≥7% from baseline was similar to placebo (NNH=112) and fewer patients experienced akathisia than placebo. Lumateperone LHH ratios were >>1 for all AEs (range 13.6–48.6) except somnolence/sedation (LHH~1).

Conclusion

Lumateperone’s benefit-risk profile was favorable in late-phase schizophrenia trials.

Funding

Intra-Cellular Therapies, Inc.
Safety and Efficacy of Aripiprazole 2-Month Ready-to-Use 960 mg in Adult Patients With Bipolar I Disorder
Authors: Madera-McDonough Jessica , Such Pedro , Yildirim Murat , McIntyre Roger S.
Published: April 2023

Background

Aripiprazole 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 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 and maintenance monotherapy treatment of BP-I [indication varies by country]). Safety and efficacy outcomes in the subpopulation of patients with BP-I are reported here.

Methods

Patients with BP-I 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 assessed at Week 32 by Clinical Global Impression – Improvement (CGI-I), Clinical Global Impression – Bipolar Version (CGI-BP), Subjective Well-being under Neuroleptic Treatment – Short Form (SWN-S), Montgomery–Åsberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS).

Results

Study completion rate was 72.5% (29/40 patients) in the Ari 2MRTU 960 group and 70.7% (29/41 patients) in the AOM 400 group. Demographics and baseline disease characteristics were generally well balanced between treatment groups. Treatment-emergent AE (TEAE) incidence was 82.5% with Ari 2MRTU 960 and 87.8% with AOM 400. The most frequent TEAEs were increased weight (Ari 2MRTU 960, 25.0%; AOM 400, 26.8%) and injection site pain (Ari 2MRTU 960, 25.0%; AOM 400, 7.3%). Mean (standard deviation [SD]) VAS score for pain after last injection was 1.2 (2.07) with Ari 2MRTU 960 and 1.3 (2.19) with AOM 400. Minimal change was seen in EPS in either group. At Week 32, mean (SD) CGI-I score was 3.1 [1.2] with Ari 2MRTU 960 and 3.2 [1.5] with AOM 400, and there was minimal mean (SD) change from baseline in CGI-BP score (Ari 2MRTU 960, -0.2 [1.0]; AOM 400, -0.6 [1.2]). Mean (SD) change from baseline in SWN-S Total score was 10.3 (16.1) with Ari 2MRTU 960 and 3.4 (21.4) with AOM 400. There was no clinically meaningful difference between the groups in MADRS Total score or YMRS Total score (difference of least squares mean change from baseline [95% confidence interval]: MADRS Total score -2.1 [-6.3, 2.1], p=0.3185; YMRS Total score 0.1 [-1.8, 2.1], p=0.8995).

Conclusions

In patients with BP-I, Ari 2MRTU 960 was generally well tolerated, and clinical stability was maintained during the study.

Funding

Otsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).
Categorical Improvement in Depressive Symptom Severity: Results From a Randomized Controlled Trial of Cariprazine for Adjunctive Treatment of MDD
Authors: Masand Prakash S. , Chen Chen , Adams Julie L. , Kramer Ken , Kerolous Majid
Published: April 2023

Background

Patients with major depressive disorder (MDD) often do not respond to antidepressant (ADT) monotherapy alone and may require adjunctive treatment to provide adequate symptom relief. Cariprazine (CAR) is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder. Post hoc analysis of data from a randomized controlled trial evaluated clinically relevant improvements in depressive symptom severity with adjunctive cariprazine in patients with MDD and inadequate response to ADT monotherapy.

Methods

Post hoc analysis evaluated data from a randomized, double-blind, placebo-controlled MDD trial (NCT03738215) in patients treated with CAR (1.5 mg/d or 3 mg/d) + ADT or placebo + ADT; the primary outcome was change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Post hoc analysis evaluated category shifts from baseline to week 6 in MADRS severity (normal <6, mild 7–19, moderate 20–34, severe ≥35). MADRS severity shifts were reported as the percentage of patients with no change or worsened severity, 1 category improvement, ≥1 category improvement, and ≥2 category improvement. Examples of categorical shifts in depressive symptoms at week 6 include change from severe at baseline to moderate (1 category improvement) and change from severe at baseline to mild (2 category improvement).

Results

Of the 751 patients in the intent-to-treat (ITT) population (CAR: 1.5 mg/d=250, 3.0 mg/d=252; placebo=249), baseline MADRS severity was mild in 1.5%, moderate in 64%, and severe in 35%. Fewer CAR + ADT patients compared to placebo + ADT had no change or worsened MADRS severity at week 6 (CAR: 1.5 mg/d=32%, 3.0 mg/d=33%; placebo=42%). Approximately 68% of patients treated with CAR + ADT demonstrated a MADRS severity improvement of 1 category or greater by week 6 (CAR: 1.5 mg/d=68%, 3.0 mg/d=67%; placebo=58%). A greater percentage of patients in the CAR 1.5 mg/d group also had a 2 or greater category improvement versus CAR 3.0 mg/d or placebo 6 (CAR: 1.5 mg/d=28%, 3.0 mg/d=17%; placebo=19%).

Conclusions

In this post hoc analysis, CAR + ADT was associated with a greater proportion of patients with improvements in depressive symptom severity categories compared with placebo + ADT. These results may suggest that CAR + ADT is associated with clinically meaningful depressive symptom improvement in MDD patients.

Funding

AbbVie
Delphi Panel on the Dimensions and Assessment of Functional Recovery in First-Episode and Early-Phase Schizophrenia Patients
Authors: Kane John M. , Yildirim Murat , Madera-McDonough Jessica , Arango Celso , Fagiolini Andrea , Gorwood Philip , Sahota Navdeep , Correll Christoph U.
Published: April 2023

Functional recovery is a treatment goal that goes beyond symptomatic remission and encompasses multiple aspects of schizophrenia patients’ lives, including quality of life, physical, and mental functioning. There is evidence that long-acting injectable (LAI) treatments promote adherence and reduce rehospitalisation and functional decline, which could facilitate patients’ ability to reach functional recovery. Despite this, LAIs are underused in the first-episode (FEP) and early-phase (EP) patient population, due to physician hesitancy and concerns around stigma. A Delphi panel was held to gain expert consensus on an approach to the domains and assessment of functional recovery elements in FEP and EP schizophrenia patients.

A literature review and input from a steering committee of 5 experts in psychiatry informed statements development for a three-round modified Delphi process. Round one was conducted via one-to-one video conference interviews, and the successive rounds were conducted via electronic surveys, which enabled international collaboration. Statements on the different domains and assessment for functional recovery were presented to 17 psychiatrists, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK), experienced in the treatment of schizophrenia with LAIs. Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists look at their previous responses in the context of the overall group.

A consensus was reached (defined a priori as ≥80% agreement) on all 27 statements covering the dimensions, assessment, and level of achieved functional recovery for FEP and EP patients. The following domains are important to consider when assessing functional recovery: depression, aggressive behaviour, social interaction, family functioning, education/employment, sexual functioning, and leisure activities. Additionally, panellists reached consensus that dimensions should be minimally impairing, if present (excluding sexual functioning) and asked about at every encounter with the patient (excluding sexual functioning and leisure activities). In summary, this Delphi panel yielded agreement that functional recovery is multidimensional and should be assessed regularly as part of usual care on an individual patient level in FEP and EP schizophrenia patients.

Funding

Lundbeck Otsuka Alliance
Delphi Panel on the Relationship Between Long-Acting Injectable Antipsychotics and Longer-Term Functional Recovery in First-Episode and Early-Phase Schizophrenia Patients
Authors: Kane John M. , Yildirim Murat , Madera-McDonough Jessica , Arango Celso , Fagiolini Andrea , Gorwood Philip , Sahota Navdeep , Correll Christoph U.
Published: April 2023

Schizophrenia is among the top ten causes of years lost due to disability. Goals of treatment are evolving beyond remission of psychotic symptoms to include physical and mental functioning, quality of life, and long-term functional recovery. Evidence has shown long-acting injectables (LAIs) are beneficial for schizophrenia patients by increasing treatment adherence and decreasing relapse and rehospitalisation. This potentially reduces disease progression and facilitates functional recovery. However, LAIs are underused and often seen as a last resort for first-episode (FEP) and early-phase (EP) patients, due to physicians’ lack of familiarity and stigma.

A three-round modified Delphi panel was held to gain expert consensus on an approach to functional recovery in FEP and EP patients with LAIs. A literature review and input from a steering committee of 5 experts in psychiatry informed the development of statements. Round one was carried out via one-to-one video conference interviews, and the subsequent rounds were conducted via electronic surveys, which enabled international collaboration. Delphi panellists were 17 psychiatrists with schizophrenia treatment experience, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK). Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendencies (mode, mean) and variability (interquartile range) of aggregated responses from the previous round were reported to panelists to understand their response in relation to the group.

There was consensus (defined a priori as ≥80% agreement) on the 8 statements relating to long-term treatment goals and LAI links to functional recovery. LAI treatment in FEP and EP patients increases adherence and reduces treatment burden and functional decline compared to the same and other oral medication. Additionally, there was consensus that LAIs lead to better treatment outcome and functional recovery. Other important factors to achieving functional recovery include patient attitude towards treatment and psychoeducation. Furthermore, consensus was reached that functional recovery and quality of life are linked. In summary, this Delphi panel yielded agreement that functional recovery is a reachable goal for FEP and EP patients and can be enhanced using LAIs.

Funding

Lundbeck Otsuka Alliance