1.Brexpiprazole for the Treatment of Agitation Associated with Dementia due to Alzheimer’s Disease: Clinical Perspectives
Hayeon KIM ; Kyung Ho LEE ; Changsu HAN ; Ashwin A. PATKAR ; Prakash S. MASAND ; Won-Myong BAHK ; Chi-Un PAE
Clinical Psychopharmacology and Neuroscience 2026;24(1):15-29
Dementia is a neuropsychiatric disorder that primarily affects the elderly, leading to a widespread decline in cognitive function and significant impairment of occupational, social, and personal functioning. In addition to cognitive deficits, dementia is frequently comorbid with behavioral and psychological symptoms of dementia (BPSD), such as agitation.When present, these secondary symptoms can exacerbate the clinical course of the disease, reduced treatment responsiveness, increased rates of admission to long-term care facilities, extended hospitalization, higher risk of personal injury and a substantial socioeconomic burden. Given these consequences, early management of BPSD—particularly agitation—is critical to mitigating these risks. Although antipsychotics are commonly prescribed to manage agitation, risperidone remains the only agent approved by regulatory authorities for this indication. Recently, however, brexpiprazole, a medication with a pharmacological profile distinct from that of risperidone, received U.S. FDA approval (on May 11, 2023) for the treatment of agitation associated with Alzheimer’s disease. Agitation is among the most prevalent BPSD manifestations, with symptoms ranging from verbal to physical aggression. Given its recent approval and unique pharmacodynamic properties, brexpiprazole may have strong potential as a therapeutic option for this population. This paper aims to review the pharmacological mechanisms, clinical evidence, and future perspectives of brexpiprazole as a novel therapeutic option for managing agitation in patients with Alzheimer’s disease.
2.Polysomnographic Evaluation of Sleep Disorders in Essential Tremor and Essential Tremor Plus: A Comparison With Healthy Controls
Ravi Prakash SINGH ; Mythirayee S ; Doniparthi Venkata SESHAGIRI ; Gulshan KUMAR ; Rohan MOHALE ; Pramod Kumar PAL ; Bindu M KUTTY ; Jitender SAINI ; Nitish L KAMBLE ; Vikram HOLLA ; Ravi YADAV
Journal of Movement Disorders 2025;18(1):45-54
Objective:
To explore sleep patterns in individuals with essential tremor (ET) and essential tremor plus (ET-Plus) compared with healthy controls and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers.
Methods:
We conducted a prospective cross-sectional study at National Institute of Mental Health and Neurosciences, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using The Essential Tremor Rating Assessment Scale (TETRAS) and Fahn‐Tolosa‐Marin Clinical Rating Scale (FTMRS). Sleep symptoms were assessed via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Mayo Sleep Questionnaire, restless legs syndrome questionnaire, Berlin questionnaire, Generalized Anxiety Disorder Scale 7, and Patient Health Questionnaire-9. All patients and controls underwent overnight video PSG. Sleep scoring was manually performed by a trained sleep research technician and the first author following the American Academy of Sleep Medicine (2017) guidelines, with data analyzed using R studio.
Results:
Compared with ET-Plus patients, ET patients had a younger onset age (46.8±11.1 years versus 30.8±16.7 years, respectively). Compared with ET patients, ET-Plus patients had higher TETRAS and FTMRS scores (p<0.005). Compared with controls, both ET patients and ET-Plus patients presented poorer sleep quality, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, and restless legs syndrome symptoms. PSG findings supported these clinical observations, showing an elevated apnea‒hypopnea index, reduced total sleep time, prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls.
Conclusion
The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients compared with healthy controls, with no differences between the ET groups.
3.Polysomnographic Evaluation of Sleep Disorders in Essential Tremor and Essential Tremor Plus: A Comparison With Healthy Controls
Ravi Prakash SINGH ; Mythirayee S ; Doniparthi Venkata SESHAGIRI ; Gulshan KUMAR ; Rohan MOHALE ; Pramod Kumar PAL ; Bindu M KUTTY ; Jitender SAINI ; Nitish L KAMBLE ; Vikram HOLLA ; Ravi YADAV
Journal of Movement Disorders 2025;18(1):45-54
Objective:
To explore sleep patterns in individuals with essential tremor (ET) and essential tremor plus (ET-Plus) compared with healthy controls and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers.
Methods:
We conducted a prospective cross-sectional study at National Institute of Mental Health and Neurosciences, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using The Essential Tremor Rating Assessment Scale (TETRAS) and Fahn‐Tolosa‐Marin Clinical Rating Scale (FTMRS). Sleep symptoms were assessed via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Mayo Sleep Questionnaire, restless legs syndrome questionnaire, Berlin questionnaire, Generalized Anxiety Disorder Scale 7, and Patient Health Questionnaire-9. All patients and controls underwent overnight video PSG. Sleep scoring was manually performed by a trained sleep research technician and the first author following the American Academy of Sleep Medicine (2017) guidelines, with data analyzed using R studio.
Results:
Compared with ET-Plus patients, ET patients had a younger onset age (46.8±11.1 years versus 30.8±16.7 years, respectively). Compared with ET patients, ET-Plus patients had higher TETRAS and FTMRS scores (p<0.005). Compared with controls, both ET patients and ET-Plus patients presented poorer sleep quality, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, and restless legs syndrome symptoms. PSG findings supported these clinical observations, showing an elevated apnea‒hypopnea index, reduced total sleep time, prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls.
Conclusion
The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients compared with healthy controls, with no differences between the ET groups.
4.Polysomnographic Evaluation of Sleep Disorders in Essential Tremor and Essential Tremor Plus: A Comparison With Healthy Controls
Ravi Prakash SINGH ; Mythirayee S ; Doniparthi Venkata SESHAGIRI ; Gulshan KUMAR ; Rohan MOHALE ; Pramod Kumar PAL ; Bindu M KUTTY ; Jitender SAINI ; Nitish L KAMBLE ; Vikram HOLLA ; Ravi YADAV
Journal of Movement Disorders 2025;18(1):45-54
Objective:
To explore sleep patterns in individuals with essential tremor (ET) and essential tremor plus (ET-Plus) compared with healthy controls and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers.
Methods:
We conducted a prospective cross-sectional study at National Institute of Mental Health and Neurosciences, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using The Essential Tremor Rating Assessment Scale (TETRAS) and Fahn‐Tolosa‐Marin Clinical Rating Scale (FTMRS). Sleep symptoms were assessed via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Mayo Sleep Questionnaire, restless legs syndrome questionnaire, Berlin questionnaire, Generalized Anxiety Disorder Scale 7, and Patient Health Questionnaire-9. All patients and controls underwent overnight video PSG. Sleep scoring was manually performed by a trained sleep research technician and the first author following the American Academy of Sleep Medicine (2017) guidelines, with data analyzed using R studio.
Results:
Compared with ET-Plus patients, ET patients had a younger onset age (46.8±11.1 years versus 30.8±16.7 years, respectively). Compared with ET patients, ET-Plus patients had higher TETRAS and FTMRS scores (p<0.005). Compared with controls, both ET patients and ET-Plus patients presented poorer sleep quality, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, and restless legs syndrome symptoms. PSG findings supported these clinical observations, showing an elevated apnea‒hypopnea index, reduced total sleep time, prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls.
Conclusion
The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients compared with healthy controls, with no differences between the ET groups.
5.Clinical Characteristics and Outcomes in Children With Severe Multisystem Inflammatory Syndrome in Children in Malaysia: A Nationwide Cohort Study
Hing Cheong Kok1 ; Dinesh Nair1 , ; Ee Vien Low2 ; Mohd Nizam Mat Bah3 ; David Chun-Ern Ng4 ; Anis Siham Zainal Abidin5,6 ; Fu Lung Khiu7 ; Huong Nai Law7 ; Heng Kiat Pung6 ; Ke Juin Wong1 ; Kwee Ching See8 ; Putri Nor Baiti Mohamad Radzi8 ; Kwai Cheng Chan9 ; Lina Lim10 ; Deenish Muniandy11 ; Nik Khairulddin Nik Yusoff12 ; Lydia Toon Muhammad Nasrun Toon3 ; Emieliyuza Yusnita Alias3 ; Pheik Sian Choong13 ; Muhammad Syarhan Nor Hadid14 ; Haema Shunmugarajoo15 ; Prakash Rao Rama Rao16 ; Siew Moy Fong1
Malaysian Journal of Medicine and Health Sciences 2025;21(No. 1):18-26
Introduction: Early identification of patients at risk for severe multisystem inflammatory syndrome in children (MIS-C)
is essential for favourable clinical outcomes. This study aims to identify the clinical characteristics, factors and outcomes associated with severe MIS-C. Materials and methods: In this retrospective cohort study involving 14 major
hospitals in Malaysia, children <15 years who met the United States Centres for Disease Control and Prevention
case definition for MIS-C were included. Severe MIS-C was defined as children who required inotropic support,
ventilatory support (invasive or non-invasive ventilation), or left ventricular ejection fraction of <55%. The factors
investigated for severe MIS-C were demographic characteristics, the presence of comorbidities, clinical characteristics, and laboratory measures. Multivariable logistic regression was used to compute the adjusted odds ratio (aORs)
of factors associated with severe MIS-C. Results: Among the 155 patients, 91 (58.7%) presented with severe MIS-C.
Severe MIS-C was more likely in patients aged ≥5 years old (aOR 2.13, 95% confidence interval [CI] 1.08-4.21), with
dehydration (aOR 3.80, 95% CI 1.53-9.45), lethargy (aOR 2.02, 95% CI 0.97-4.18), tachycardia (aOR 8.33, 95% CI
3.27-21.22), albumin <30g/L (aOR 3.36, 95% CI 1.58-7.13), creatine kinase >200U/L (aOR 3.68, 95% CI 1.57-8.64),
D-dimer >3.0µg/mL (aOR 2.11, 95% CI 1.08-4.13), ferritin >500ng/mL (aOR 3.77, 95% CI 1.88-7.55), prothrombin
time >12.7 seconds (aOR 3.22, 95% CI 1.61-6.43), and urea >6mmol/L (aOR 5.09, 95% CI 2.04-12.71). Conclusion:
Identification of these associated factors of severity in MIS-C could aid in early recognition and prompt escalation of
care, leading to better outcomes.
6.Pericoronary Adipose Tissue as a Predictor of Diastolic Dysfunction:A New Paradigm in Coronary Artery Disease Assessment
Ritika AGARWAL ; Jahnavi GADUPUTI ; Karthik R. SHETTY ; Neeraj SHIVAKUMAR ; V. S. PRAKASH
International Journal of Heart Failure 2025;7(4):229-239
Background and Objectives:
Pericoronary adipose tissue (PCAT) is linked to coronary artery disease (CAD) progression through compositional changes that disrupt adipose homeostasis and affect vascular biology. This study explores how PCAT characteristics - volume and fat attenuation index (FAI)-relate to CAD severity and left ventricular (LV) function.
Methods:
This study included 100 patients with suspected CAD who underwent coronary computed tomography angiography (CCTA) and echocardiography between September 2023 and July 2024. PCAT volume, FAI and thickness were measured along coronary arteries (right coronary artery [RCA], left anterior descending [LAD], and left circumflex [LCX]). CAD severity was assessed using the Gensini score, while LV structural and functional metrics, including diastolic function, were obtained via echocardiography. Correlations between PCAT parameters, CAD burden, and LV function were analyzed using Spearman’s correlation and p value <0.05 was considered significant.
Results:
RCA FAI exhibited the strongest association with CAD severity (Gensini score: r=0.416, p=0.026) and diastolic dysfunction (r=0.536, p<0.001), with progressively less negative values from Grade 1 to Grade 3 dysfunction. LAD and LCX (r=0.278, p=0.03) FAI displayed moderate associations. RCA volume correlated with LV mass index, fractional shortening and diastolic parameters. Hypertension was associated with elevated RCA FAI and volume (p<0.05), while diabetes showed no significant impact on PCAT metrics.
Conclusions
PCAT FAI is a sensitive marker of CAD severity and diastolic dysfunction, especially in the RCA, highlighting its value for detection, risk stratification, and personalized CAD management. Integration of PCAT metrics into routine CCTA analysis could enhance cardiovascular risk assessment and treatment planning.
7.Elevated Homocysteine Level and Brain Atrophy Changes as Markers to Screen the Alzheimer Disease: Case Series
Ram Prakash SAH ; C. S. VIDYA ; Pratibha PEREIRA ; Shubha JAYARAM ; Anshu Kumar YADAV ; P. SUJATHA
Annals of Geriatric Medicine and Research 2024;28(1):116-120
Alzheimer disease (AD) is the most common cause of dementia worldwide. Its clinical manifestations include a progressive loss of memory and other cognitive domains, as well as brain atrophy. An elevated homocysteine level (>15 µmol/L), known as hyperhomocysteinemia, is also an attributing risk factor for AD, vascular pathologies, and brain atrophy. Neuroimaging studies including T2-weighted magnetic resonance imaging scans revealed white matter hyperintensities in the periventricular and deep white matter, enlarged ventricles, widened sulci, and decreased white matter mass, which are features of aging, as well as cerebrovascular changes. This case series investigated changes in biochemical marker levels including serum homocysteine, folate, and vitamin B12, and the degree of atrophic variations in cortical-subcortical white matter in AD. The present study hypothesized that serum homocysteine levels might be used as a surrogate marker to screen for AD at an earlier stage.
8.The Potential Role of Aripiprazole Augmentation for Major Depressive Disorder with Anxious Distress in Naturalistic Treatment Setting
Seung-Hoon LEE ; Kyung Ho LEE ; Tae Sun HAN ; Changsu HAN ; Won-Myong BAHK ; Soo-Jung LEE ; Ashwin A. PATKAR ; Prakash S. MASAND ; Chi-Un PAE
Clinical Psychopharmacology and Neuroscience 2024;22(2):370-375
Objective:
This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice.
Methods:
Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved.
Results:
The changes of primary endpoint HAMA (t = 5.731, −4.6, p = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, −3.4, p < 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, −0.9, t = 1.821, p = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, −0.4, p < 0.001) scores were also significantly improved during the study. No significant adverse events were observed.
Conclusion
This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.
9.Nutrient Drink Test to Assess Gastric Accommodation in Cyclic Vomiting Syndrome: Single-blinded Parallel Grouped Prospective Study
Afrin N KAMAL ; Kevin B HARRIS ; Shashank SARVAPALLI ; Gregory S SAYUK ; C Prakash GYAWALI ; Scott GABBARD
Journal of Neurogastroenterology and Motility 2023;29(1):65-71
Background/Aims:
Cyclic vomiting syndrome (CVS) is characterized by episodes of nausea and vomiting, separated by symptom-free intervals. The pathogenesis of CVS is poorly understood. Limited data exist on evaluating impaired gastric accommodation as a mechanistic means for symptoms. We aim to determine if CVS patients demonstrate impaired gastric accommodation applying a nutrient drink test (NDT) protocol.
Methods:
Through this single-blinded pilot clinical trial, patients with CVS per Rome IV critera and healthy controls were assessed for presence of impaired gastric accommodation by administering an established NDT protocol. Statistical analysis was performed, with data presented as medians and interquartile range.
Results:
Eleven CVS patients and 15 healthy controls participated in the study between January 2018 and October 2018. Median age was 42.0 years and 37.0 years; majority of subjects were female, 72.7% and 73.3%, respectively. Demographics were similar between CVS and healthy controls. Almost all healthy controls (93.3%) ingested the complete 500 mL protocol, whereas a smaller proportion (72.7%) were able to complete all 4 doses in the CVS group (P = 0.188). Post-prandial visual analogue scale scores of nausea and abdominal pain were found to be significantly higher in CVS patients compared to healthy controls.
Conclusions
To our knowledge, this is the first NDT protocol in CVS evaluating the role of impaired gastric accommodation and hypersensitivity as a possible pathophysiologic mechanism. Findings from this study suggest the presence of gastric hypersensitivity in a subset of CVS patients. These results provide the foundational data necessary for future larger testing of NDT and diagnostic accuracy in CVS.
10.Efficacy and Safety of Escitalopram, Desvenlafaxine, and Vortioxetine in the Acute Treatment of Anxious Depression: A Randomized Rater-blinded 6-week Clinical Trial
Cheolmin SHIN ; Sang Won JEON ; Seung-Hoon LEE ; Chi-Un PAE ; Narei HONG ; Hyun Kook LIM ; Ashwin A. PATKAR ; Prakash S. MASAND ; Hyonggin AN ; Changsu HAN
Clinical Psychopharmacology and Neuroscience 2023;21(1):135-146
Objective:
Anxious depression is associated with greater chronicity, higher severity of symptoms, more severe functional impairment, and poor response to drug treatment. However, evidence for first-choice antidepressants in patients with anxious depression is limited. This study aimed to compare the efficacy and safety of escitalopram, desvenlafaxine, and vortioxetine in the acute treatment of anxious depression.
Methods:
Patients (n = 124) with major depressive disorder and high levels of anxiety were randomly assigned to an escitalopram treatment group (n = 42), desvenlafaxine treatment group (n = 40), or vortioxetine treatment group (n = 42) in a 6-week randomized rater-blinded head-to-head comparative trial. Changes in overall depressive and anxiety symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), respectively.
Results:
Patients demonstrated similar baseline-to-endpoint improvement in scores and similar response and remission rates for HAMD and HAMA. Analysis of the individual HAMD items revealed that desvenlafaxine significantly reduced anxiety somatic scores (p= 0.013) and hypochondriasis scores (p = 0.014) compared to escitalopram. With respect to the individual HAMA items, desvenlafaxine treatment showed significantly lower scores for respiratory symptoms (p = 0.013) than escitalopram treatment and cardiovascular symptoms (p = 0.005) than vortioxetine treatment. The treatments were well tolerated, with no significant differences.
Conclusion
Our results indicated no significant differences in the efficacy and tolerability of escitalopram, desvenlafaxine, and vortioxetine in this subtype of patients with anxious depression during the acute phase of treatment.


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