bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundLumateperone 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).MethodsData 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.ResultsIn 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).ConclusionLumateperone’s benefit-risk profile was favorable in late-phase schizophrenia trials.FundingIntra-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

AbstractBackgroundAripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months. This 32-week trial evaluated the safety, pharmacokinetics, and efficacy of multiple-dose administration of Ari 2MRTU 960 in clinically stable adults with schizophrenia or 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.MethodsPatients 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).ResultsStudy 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).ConclusionsIn patients with BP-I, Ari 2MRTU 960 was generally well tolerated, and clinical stability was maintained during the study.FundingOtsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).
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

AbstractBackgroundPatients 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.MethodsPost 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).ResultsOf 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%).ConclusionsIn 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.FundingAbbVie
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

AbstractFunctional 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.FundingLundbeck 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

AbstractSchizophrenia 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.FundingLundbeck Otsuka Alliance
Pharmacokinetic Profile of Aripiprazole 2-Month Ready-to-Use 960 mg in Adult Patients With Schizophrenia or Bipolar I Disorder
Authors: Harlin Matthew , Yildirim Murat , Such Pedro , Madera-McDonough Jessica , Larsen Frank 
Published: April 2023

AbstractIntroductionAripiprazole 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, intended for the treatment of schizophrenia and maintenance monotherapy treatment of bipolar I disorder (BP-I). This 32-week trial evaluated the safety, tolerability, and pharmacokinetic profile of multiple-dose administration of Ari 2MRTU 960 in clinically stable adult patients with a diagnosis of schizophrenia or BP-I, versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the treatment of schizophrenia and maintenance monotherapy treatment of BP-I).MethodsThis was an open-label, multiple-dose, randomized, parallel-arm trial conducted at 16 sites in the US. Patients were randomized to receive Ari 2MRTU 960 every 56±2 days (n=132) or AOM 400 every 28±2 days (n=134). The primary objective was to establish the similarity of aripiprazole concentrations on the last day of the dosing interval, as well as exposure during the dosing interval (area under the concentration-time curve [AUC]), between Ari 2MRTU 960 and AOM 400 following multiple doses. It was pre-specified that the lower bound of the 90% confidence interval (CI) of the geometric means ratio (GMR) for these parameters must be >0.8.ResultsIn the Ari 2MRTU 960 group, 102 patients (77.3%) completed the study; in the AOM 400 group, 92 patients (68.7%) completed the study. The GMR of C56 for Ari 2MRTU 960 to C28 for AOM 400 was 1.011 (90% CI: 0.893, 1.145). The GMR (90% CI) of AUC0–56 for Ari 2MRTU 960 to AUC0–28 for AOM 400 was 1.006 (90% CI: 0.851, 1.190). Mean (standard deviation) maximum aripiprazole plasma concentration was 342 (157) ng/ml after the fourth Ari 2MRTU 960 dose and 344 (212) ng/ml after the eighth AOM 400 dose.ConclusionPharmacokinetic parameters were similar between Ari 2MRTU 960 and AOM 400.FundingOtsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).
The Bitter Touch: Acquired Tactile-Gustatory Synesthesia
Authors: Sadana Sabina , Ratra Raunaq Singh , Kainth Harman , Nijhar Pukhraj Singh , Sahni Manmeet Singh , Hirsch Alan 
Published: April 2023

AbstractIntroductionGustatory sensation in response to tactile stimulation has been reported to occur in only 0.6% of synesthetes and has rarely been formally described.MethodsCase Study: A 29-year-old female with schizoaffective disorder – depressed subtype, two months prior to presentation, began noticing that when she touched objects, she would experience an abnormal taste in her mouth. When she would touch specific items with her fingertips, for instance wood, bedsheets, tables, cups, plates, silverware, metal, trash cans, and toothpaste would induce a bitter taste. Touching wood caused the most intense bitter taste. Touching glass did not precipitate a taste.ResultsMental Status Examination: Disheveled and guarded with minimal eye contact. Anxious and agitated. She believes people are stalking her and that cell phones, radios, and computers emit radiation which makes her head burn as if it is on fire. She perceived that inanimate objects, such as furniture, were staring at her. Other: CT scan of brain with and without contrast: normal.DiscussionThis could be due to neural overactivation between brain regions due to a neighborhood effect, with cross-firing of connecting fibers. The cortical taste area of the brain lies within the Brodmann area 43 of the parietal lobe which includes the pre- as well as post-central gyri extending into the parietal operculum. Brodmann areas 3, 1, and 2 in the postcentral gyrus is where the primary sensation for touch is mediated. The stimulation in adjacent and overlapping anatomical structures may be explained by ephaptic transmission with firing of one causing discharge of the second, yclept the adjacency principle.This co-localization hypothesis is further supported by the occurrence of pathological state of seizures which manifest both tactile and gustatory sensation. Such a hypothesis would be supported by Anderson’s 1886 observation discussing a peculiar sensation in the right arm and hand elicited concurrently with a bitter sensation in the mouth. Through an overflow phenomenon, touch may induce a diffuse serotonergic discharge to more remote regions of the brain that may mediate their functions through serotonin, such as taste. Possibly, other pathology may be invoked to explain this synesthesia. A deprived sensory system may be hyper-receptive to stray or overflow of sensations which are then interpreted within the sensorily deprived sensory system, as in Charles Bonnet syndrome. In the chemosensory sphere, sensory deprivation is associated with chemosensory hallucinations. If the patient manifests gustatory deficit, it may have predisposed her to sensitivity to such stray or overflowing sensory stimulus from touch manifesting as gustation. In those who present with synesthesia, investigation of pathology in the sensory system of the receiving concurrent sensation is warranted.FundingNo Funding
Impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA Receptor Antagonist, on Anhedonic Symptoms in Major Depressive Disorder
Authors: Jones Amanda , McIntyre Roger S. , Jacobsen Mark , Streicher Caroline , Thomas Zachariah , Tabuteau Herriot 
Published: April 2023

AbstractBackgroundTreatments for MDD that can improve both overall depressive and anhedonic symptoms are urgently needed.AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.ObjectiveTo evaluate the effect of AXS-05 in improving anhedonic symptoms in MDD.MethodsGEMINI (N=327) was a randomized, double-blind, placebo-controlled, 6-week study, which randomized adults with MDD to AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) or placebo, twice daily. The primary endpoint was change from baseline in the MADRS total score at Week 6. A post-hoc analysis was conducted to determine the impact of AXS-05 versus placebo on the 5-item MADRS anhedonia subscale (MAS).ResultsBaseline MAS scores were 19.8 and 19.6 in the AXS-05 and placebo group, respectively. At Week 1, AXS-05 treatment resulted in a significant mean reduction from baseline in the MAS score of 4.44 versus 2.69 points for placebo (p< 0.001). At Week 6, the mean reduction from baseline in the MAS was 9.70 for AXS-05 compared to 7.22 for placebo (p=0.001). Response rates (≥ 50% MAS improvement) were significantly greater for AXS-05 compared to placebo at Week 1 (p< 0.001) and at every time point thereafter.Treatment with AXS-05 was generally safe and well tolerated. The most common adverse events being dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.ConclusionsTreatment with AXS-05 rapidly and significantly reduced anhedonic symptoms as well as overall depressive symptoms.FundingAxsome Therapeutics
Candidates, voters, and voting advice applications
Authors: Tromborg Mathias Wessel , Albertsen Andreas 
Published: April 2023

AbstractVoters often face a complex information environment with many options when they vote in elections. Research on democratic representation has traditionally been skeptical about voters’ ability to navigate this complexity. However, voting advice applications (VAAs) offer voters a shortcut to compare their own preferences across numerous issues with those of a large number of political candidates. As VAAs become more prevalent, it is critical to understand whether and how voters use them when they vote. We analyze how VAA users process and use VAA information about their district candidates with original survey data from the 2019 Danish parliamentary election in collaboration with the administrators of one of the most widely used Danish VAAs. The results demonstrate that VAAs have substantively large effects on their users’ choices between parties and between candidates within parties.
Modulation of Energetic Electron Precipitation Driven by Three Types of Whistler Mode Waves
Authors: Shen Xiao‐Chen , Li Wen , Capannolo Luisa , Ma Qianli , Qin Murong , Artemyev Anton V. , Angelopoulos Vassilis , Zhang Xiao‐Jia , Huang Sheng 
Published: April 2023

AbstractPrecipitation into the Earth's atmosphere due to pitch angle scattering by plasma waves has been recognized as one of the major loss mechanisms for energetic electrons. In this study, we quantitatively evaluate their roles in precipitating electrons during a conjunction event with modulated electron precipitation observed at low altitudes by Electron Loss and Fields INvestigation and three types of whistler mode waves (hiss, plume hiss, and chorus) measured near the equator by Time History of Events and Macroscale Interactions during Substorms. Electron precipitation was observed from ∼50 keV to <1 MeV with a spatial modulation, suggested by a good correlation between L shell‐sorted precipitation fluxes and wave intensities. A quasi‐linear analysis supports the observed energy range of precipitation and the ratio of precipitating‐to‐trapped flux. Our findings reveal that the modulated energetic electron precipitation is driven by hiss, plume hiss, and chorus waves.