Clusterization of Behavioral and Psychological Symptoms of Dementia as Assessed by Neuropsychiatric Inventory: A Case Against the Use of Principal Component Analysis.

Background: The term Behavioral and Psychological Symptoms of Dementia (BPSD) covers a group of phenomenologically and medically distinct symptoms that rarely occur in isolation. Their therapy represents a major unmet medical need across dementias of different types, including Alzheimer's disease. Understanding of the symptom occurrence and their clusterization can inform clinical drug development and use of existing and future BPSD treatments. Objective: The primary aim of the present study was to investigate the ability of a commonly used principal component analysis to identify BPSD patterns as assessed by Neuropsychiatric Inventory (NPI). Methods: NPI scores from the Aging, Demographics, and Memory Study (ADAMS) were used to characterize reported occurrence of individual symptoms and their combinations. Based on this information, we have designed and conducted a simulation experiment to compare Principal Component analysis (PCA) and zero-inflated PCA (ZI PCA) by their ability to reveal true symptom associations. Results: Exploratory analysis of the ADAMS database revealed overlapping multivariate distributions of NPI symptom scores. Simulation experiments have indicated that PCA and ZI PCA cannot handle data with multiple overlapping patterns. Although the principal component analysis approach is commonly applied to NPI scores, it is at risk to reveal BPSD clusters that are a statistical phenomenon rather than symptom associations occurring in clinical practice. Conclusions: We recommend the thorough characterization of multivariate distributions before subjecting any dataset to Principal Component Analysis.

Diagnosis of behavioral symptoms as a predictor of institutionalization among Medicaid patients with dementia.

OBJECTIVES: Behavioral symptoms are commonly observed in the course of dementia. This study aimed to assess the association of the diagnosis of a cluster of behavioral symptoms (e.g., agitation, aggression, psychotic symptoms, and delirium/wandering) with the likelihood of subsequent institutionalization. METHODS: A retrospective cohort study of adults aged 65 and above diagnosed with dementia identified in the IBM® MarketScan® Multistate Medicaid database between October 01, 2015, and September 30, 2019, was conducted. The index date was defined as the first diagnosis date of dementia. The presence or absence of behavioral symptoms was identified in the 6 months prior to the index date (baseline). Institutionalization was evaluated 12 months (follow-up) post the index date. The association between diagnosed behavioral symptoms during the baseline period and institutionalization in the follow-up period was assessed using a multivariable logistic regression, adjusting for baseline sociodemographic and clinical characteristics. RESULTS: The study cohort included 40,714 patients with dementia. A diagnosis of behavioral symptoms was found among 2,067 (5.1%) patients during the baseline period. An increased likelihood of institutionalization was found during the follow-up among patients with agitation and aggression in baseline (OR = 1.51 (95% CI: 1.18-1.92)) compared to patients without these symptoms at baseline. Patients with psychotic symptoms in baseline had significantly higher odds of getting institutionalized during the follow-up compared to patients without psychotic symptoms in baseline (OR = 1.36 (95% CI: 1.20-1.54)). Similarly, patients with symptoms of delirium and wandering in baseline had a higher likelihood of institutionalization than patients without these symptoms at baseline (OR = 1.61 (95% CI: 1.30-1.99)). CONCLUSION: Several diagnosed behavioral symptoms were associated with a higher risk of institutionalization among older adults with dementia and should be considered when planning treatment strategies for the effective management of the condition.

Effect of Nordic Sensi® Chair on Behavioral and Psychological Symptoms of Dementia in Nursing Homes Residents: A Randomized Controlled Trial.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are present in most people with dementia (PwD), including Alzheimer's disease. There is consensus that non-pharmacological therapies represent the first line of treatment to address BPSD. OBJECTIVE: We explore the efficacy of the use of a rocking chair (Nordic Sensi® Chair, NSC) in the treatment of BPSD in nursing home residents with moderate and severe dementia. METHODS: We carried out a 16-week randomized, single-blind, controlled, clinical trial with PwD admitted to nursing homes. Participants were assigned to a treatment group (n = 40) that received three times a week one session per day of 20 minutes in the NSC and a control group (n = 37). The Neuropsychiatric Inventory-Nursing Home (NPI-NH) was used as primary efficacy outcome. Occupational distress for the staff was evaluated using the NPI-NH Occupational Disruptiveness subscale (NPI-NH-OD). Statistical analyses were conducted by means of a Mixed Effects Model Analysis. RESULTS: Treatment with the NSC was associated with a beneficial effect in most of BPSD, as reflected by differences between the treatment and control group on the NPI-NH total score (mean change score -18.87±5.56 versus -1.74±0.67, p = 0.004), agitation (mean change score -2.32±2.02 versus -0.78±1.44, p = 0.003) and irritability (mean change score -3.35±2.93 versus -1.42±1.31, p = 0.004). The NPI-NH-OD total score also improved the most in the treatment group (mean change score -9.67±7.67 versus -7.66±6.08, p = 0.003). CONCLUSIONS: The reduction in overall BPSD along with decreased caregiver occupational disruptiveness represent encouraging findings, adding to the potential of nonpharmacological interventions for nursing home residents living with dementia.

'There's no straight line ' a consumer-informed intervention for FTD family care partners: the STELLA-FTD pilot study.

OBJECTIVES: Behavioral symptoms and communication challenges are particularly apparent in frontotemporal degenerative (FTD) dementias. There is a paucity of psychoeducation programming specifically tailored to the needs of families with FTD. We revised an existing intervention to meet the needs of these families. METHODS: We used a quasi-experimental approach. In Phase 1, we sought consumer input about an existing intervention. In Phase 2, we modified the intervention based on the qualitative findings from Phase 1 and tested the revised intervention (STELLA-FTD) for feasibility, acceptability and early-stage efficacy. Outcome for Phase 2 included feasibility data and care partner reactivity to upsetting behaviors. Secondary outcomes included data from unobtrusive sleep monitoring. An inductive analysis of transcripts from the Phase 2 STELLA-FTD focus group provides guidance for future revisions. RESULTS: Fifteen family care partners participated in the Phase 1 focus groups; sixteen care partners enrolled in Phase 2. Testing in Phase 2 revealed that the care partners found our consumer-informed revised intervention both feasible and acceptable. The post-intervention findings suggest STELLA-FTD has the potential to reduce care partner reactivity to upsetting behaviors and to decrease care partner burden. Sleep did not change over the 8-week intervention. CONCLUSIONS: The revised STELLA-FTD intervention was found to be feasible and acceptable, and has potential to improve care partner burden for families living with FTD. Providing the intervention via telehealth maximized access and engaged rehabilitation specialists in providing disease management content. Future revisions will include examination of efficacy and mechanism of action (OHSU IRB # 00022721, ClinicalTrials.gov NCT05338710).

Economic outcomes associated with diagnosed behavioral symptoms among patients with dementia in the United States: a health care claims database analysis.

BACKGROUND: Behavioral symptoms are common in patients with dementia. However, there is limited evidence of their economic burden. Among commercially insured patients with dementia in the United States, this study assessed the prevalence of diagnosed behavioral symptoms and whether healthcare resources utilization and costs were associated with these symptoms. METHODS: This retrospective observational study was conducted using the IBM® MarketScan® Commercial Claims and Encounters and Medicare Supplemental database from October 1, 2015, to September 30, 2019. Diagnoses of dementia and behavioral symptoms were identified using the International Classification of Diseases, 10th Modification codes. To test differences in patient characteristics among those with and without diagnosed behavioral symptoms, t-tests were used for continuous variables, and chi-square tests were used for categories. Generalized linear models were used to compare healthcare resource utilization and costs between patients with and without diagnosed behavioral symptoms, adjusted for baseline characteristics. RESULTS: Of the 62,901 patients with dementia included in the analysis, 16.5% had diagnosed behavioral symptoms 12 months post dementia diagnosis. Patients with diagnosed behavioral symptoms used more health care resources (mean annual pharmacy visits per patient: 39.83 vs. 33.08, mean annual outpatient visits per patient: 24.20 vs. 16.94, mean annual inpatient visits per patient: 0.98 vs. 0.47, mean annual ER visits per patient: 2.45 vs. 1.21) and incurred higher cost of care than those without diagnosed behavioral symptoms (mean annual total health care costs per patients: $63,268 versus $33,383). Inpatient care was the most significant contributor to total costs (adjusted annual mean cost per patient: $28,195 versus $12,275). CONCLUSION: Behavioral symptoms were significantly associated with higher healthcare resource utilization and costs among patients with dementia. Further research is warranted to address the unmet medical needs of this patient population.

Challenges of Agitation in Dementia: A Plea for Early Discussion.

ABSTRACT: Behavioral and psychological symptoms of dementia (BPSD) occur frequently among people with dementia and are known precipitants for placement in care facilities. Despite the social, financial, and psychological impact on dementia care, education and discussions on BPSD have not been routinely included in advance care planning (ACP). As a result, families can face great challenges in making complex medical decisions when their loved ones are admitted to the geriatric psychiatric inpatient unit with refractory BPSD. We present the case of an 83-year-old gentleman with BPSD to illustrate universal struggles in dementia care experienced by many families, which could have been alleviated by education and discussions around BPSD earlier in the patient's dementia course. A literature search did not yield any articles that mention discussions of BPSD in ACP. The lack of literature referencing BPSD in ACP supports our clinical experiences with the case and highlights the need for improvement in current dementia care. We propose a guideline for providers to facilitate conversations around BPSD as an integral part of ACP, including discussions of four key points related to the progressive nature of dementia, the commonality of BPSD, the lack of FDA-approved treatment for BPSD, and the difficulty in balancing agitation and sedation to allow safe placement. We firmly believe it is important to start discussion on BPSD as part of ACP as early as possible. Early education and discussion will help to facilitate meaningful care decisions as patients and families navigate the challenges associated with this progressive disease.

Development and Validation of a Knowledge Scale About the Behavioral and Psychological Symptoms of Dementia (KS-BPSD) Among Chinese Formal Caregivers.

OBJECTIVES: The current study aimed to develop a scale assessing knowledge about behavioral and psychological symptoms of dementia (KS-BPSD) among Chinese formal caregivers and to investigate its psychometric properties and factorial structure. METHODS: The scale was generated with a systematic development process, and 229 formal caregivers working at nursing homes were recruited to construct and assess the psychometric properties of the scale. The preliminary scale was reviewed by an expert panel and items were selected based on item discrimination, difficulty, and item-total correlation. RESULTS: The final KS-BPSD version consisted of 12 items, loaded into three factors (i.e., Disease Characteristics, Care and Risks, and Treatment Needs) following principal component analysis (PCA). The KS-BPSD showed good test-retest reliability, internal consistency, as well as construct and concurrent validity. CONCLUSIONS: The 12-item KS-BPSD was found to have high reliability and preliminary validity in assessing the level of knowledge about patient's BPSD among formal Chinese caregivers in nursing homes. CLINICAL IMPLICATIONS: KS-BPSD is a reliable tool to address the knowledge discrepancies and support needs among dementia caregivers, helping to develop and evaluate educational programs in the management of patient's BPSD.

Early Identification of Different Behavioral Phenotypes in the Behavioral Variant of Frontotemporal Dementia with the Aid of the Mini-Frontal Behavioral Inventory (mini-FBI).

BACKGROUND: The Frontal Behavioral Inventory (FBI) is a questionnaire designed to quantify behavioral changes in frontotemporal dementia (FTD). Literature showed heterogeneous FBI profiles in FTD versus Alzheimer's disease (AD) with variable occurrence of positive and negative symptoms. OBJECTIVE: In this study, we constructed a short FBI version (i.e., mini-FBI) with the aim to provide clinicians with a brief tool for the identification of early behavioral changes in behavioral variant of FTD (bvFTD), also facilitating the differential diagnosis with AD. METHODS: 40 bvFTD and 33 AD patients were enrolled. FBI items were selected based on internal consistency and exploratory factor analysis. Convergent validity of mini-FBI was also assessed. A behavioral index (i.e., B-index) representing the balance between positive and negative mini-FBI symptoms was computed in order to analyze its distribution in bvFTD through a cluster analysis and to compare performance among patient groups. RESULTS: The final version of the mini-FBI included 12 items, showing a significant convergent validity with the Neuropsychiatric Inventory scores (rp = 0.61, p < 0.001). Cluster analysis split patients in four clusters. bvFTD were included in three different clusters characterized by prevalent positive symptoms, both positive and negative symptoms, or prevalent negative behavioral alterations, similar to a subset of AD patients. A fourth cluster included only AD patients showing no positive symptoms. CONCLUSION: The mini-FBI is a valuable easily administrable questionnaire able to early identify symptoms effectively contributing to the bvFTD behavioral syndrome, aiding clinician in diagnosis and management.

Sex influences clinical phenotype in frontotemporal dementia.

INTRODUCTION: Frontotemporal dementia (FTD) encompasses a wide spectrum of genetic, clinical, and histological findings. Sex is emerging as a potential biological variable influencing FTD heterogeneity; however, only a few studies explored this issue with nonconclusive results. OBJECTIVE: To estimate the role of sex in a single-center large cohort of FTD patients. METHODS: Five hundred thirty-one FTD patients were consecutively enrolled. Demographic, clinical, and neuropsychological features, survival rate, and serum neurofilament light (NfL) concentration were determined and compared between sex. RESULTS: The behavioral variant of FTD was more common in men, whereas primary progressive aphasia was overrepresented in women (p < 0.001). While global cognitive impairment was comparable, females had a more severe cognitive impairment, namely in Trail Making Test parts A and B (p = 0.003), semantic fluency (p = 0.03), Short Story Recall Test (p = 0.003), and the copy of Rey Complex Figure (p = 0.005). On the other hand, men exhibited more personality/behavioral symptoms (Frontal Behavior Inventory [FBI] AB, p = 0.003), displaying higher scores in positive FBI subscales (FBI B, p < 0.001). In particular, apathy (p = 0.02), irritability (p = 0.006), poor judgment (p = 0.033), aggressivity (p = 0.008), and hypersexuality (p = 0.006) were more common in men, after correction for disease severity. NfL concentration and survival were not statistically different between men and women (p = 0.167 and p = 0.645, respectively). DISCUSSION: The present study demonstrated that sex is a potential factor in determining FTD phenotype, while it does not influence survival. Although the pathophysiological contribution of sex in neurodegeneration is not well characterized yet, our findings highlight its role as deserving biological variable in FTD.

Behavioural and psychological symptoms of early-onset and late-onset Alzheimer's disease among Chinese adults: analysis of modifiable factors.

BACKGROUND: To conduct a comprehensive comparison of behavioural and psychological symptoms of dementia (BPSD) in Chinese people with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) and analyse the factors of differences. METHODS: A cross-sectional survey of 93 EOAD and100 LOAD and their caregivers in China from November 2018 to May 2019. RESULTS: The total Neuropsychiatric Inventory score was significantly higher in LOAD. A higher level of agitation in EOAD was related to a lower quality of life of caregivers and the emotional expression of ignoring people with dementia. Higher euphoria scores in LOAD were associated with reduced negative coping by caregivers and reduced stability and predictability at home. CONCLUSION: The early identification and management of specific BPSD of EOAD and LOAD by family members and health professionals may improve the quality of care and life for people with dementia and that of caregivers.

Most families tend to realize progress of Alzheimer's disease when behavioural and psychological symptoms are obvious.

BACKGROUND: Alzheimer's disease (AD) is a common cognitive disease that can progress at an accelerating rate. Even with early diagnosis, the families might not recognize AD progressing unless behavioural and psychological symptoms of dementia (BPSD) develop. In many cases, discrepancies could exist between family-assessed AD stage and diagnosed AD stage. This study explored such discrepancies and potential clinical implications. METHODS: Participants were 161 new outpatients with AD or mild cognitive impairment at four memory clinics whose AD stage was diagnosed using the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). We classified patients into four groups according to AD severity. Family members completed the Functional Assessment Staging (FAST) scale during an interview. We then assigned patients to three groups according to discrepancies between family-assessed and diagnosed AD stage. Families also completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), which assesses 12 neuropsychiatric domains, in order to examine the presence of BPSD in relation to AD stage. RESULTS: Most families (74%-80%) assessed patients as having milder AD than the diagnosed stage. NPI-Q scores and duration of education significantly affected discrepancies with HDS-R and MMSE scores. The NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance significantly affected family-assessed FAST. Families of patients with more years of education assessed the AD stage as more advanced than the diagnosed stage. Surprisingly, living together did not significantly affect the discrepancy. CONCLUSIONS: Most families assessed AD as milder than the clinically diagnosed AD stage. In addition, high NPI-Q scores and more years of school education significantly affected the discrepancy. Family-assessed FAST was significantly affected by the NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance. These results suggest that obvious BPSD are significant factors for Japanese families to recognize AD progress.

Gait analysis as a robust pain behavioural endpoint in the chronic phase of the monoiodoacetate-induced knee joint pain in the rat.

The monoiodoacetate-induced rat model of osteoarthritis knee pain is widely used. However, there are between-study differences in the pain behavioural endpoints assessed and in the dose of intraarticular monoiodoacetate administered. This study evaluated the robustness of gait analysis as a pain behavioural endpoint in the chronic phase of this model, in comparison with mechanical hyperalgesia in the injected (ipsilateral) joint and development of mechanical allodynia in the ipsilateral hind paws. Groups of Sprague-Dawley rats received a single intraarticular injection of monoiodoacetate at 0.5, 1, 2 or 3 mg or vehicle (saline) into the left (ipsilateral) knee joint. An additional group of rats were not injected (naïve group). The pain behavioural methods used were gait analysis, measurement of pressure algometry thresholds in the ipsilateral knee joints, and assessment of mechanical allodynia in the ipsilateral hind paws using von Frey filaments. These pain behavioural endpoints were assessed premonoiodoacetate injection and for up to 42-days postmonoiodoacetate injection in a blinded manner. Body weights were also assessed as a measure of general health. Good general health was maintained as all rats gained weight at a similar rate for the 42-day study period. In the chronic phase of the model (days 9-42), intraarticular monoiodoacetate at 3 mg evoked robust alterations in multiple gait parameters as well as persistent mechanical allodynia in the ipsilateral hind paws. For the chronic phase of the monoiodoacetate-induced rat model of osteoarthritis knee pain, gait analysis, such as mechanical allodynia in the ipsilateral hind paws, is a robust pain behavioural measure.

A randomized trial of online single-session interventions for adolescent depression during COVID-19.

The COVID-19 pandemic has potentially increased the risk for adolescent depression. Even pre-pandemic, <50% of youth with depression accessed care, highlighting needs for accessible interventions. Accordingly, this randomized controlled trial (ClinicalTrials.gov: NCT04634903 ) tested online single-session interventions (SSIs) during COVID-19 in adolescents with elevated depression symptoms (N = 2,452, ages 13-16). Adolescents from all 50 US states, recruited via social media, were randomized to one of three SSIs: a behavioural activation SSI, an SSI teaching that traits are malleable and a supportive control. We tested each SSI's effects on post-intervention outcomes (hopelessness and agency) and three-month outcomes (depression, hopelessness, agency, generalized anxiety, COVID-19-related trauma and restrictive eating). Compared with the control, both active SSIs reduced three-month depressive symptoms (Cohen's d = 0.18), decreased post-intervention and three-month hopelessness (d = 0.16-0.28), increased post-intervention agency (d = 0.15-0.31) and reduced three-month restrictive eating (d = 0.12-17). Several differences between active SSIs emerged. These results confirm the utility of free-of-charge, online SSIs for high-symptom adolescents, even in the high-stress COVID-19 context.

Behavioural Impairment and Frontotemporal Dementia in Oculopharyngeal Muscular Dystrophy.

Some patients with Oculopharyngeal Muscular Dystrophy (OPMD) develop frontotemporal dementia (FTD). The prevalence and clinical correlates of behavioural impairment, including FTD, is unknown in OPMD.24 OPMD patients and their proxies completed a questionnaire concerning behavioural impairment (ALS-FTD-Q). We examined proportions with mild or severe behavioural changes, according to validated cut-off proxy scores. We examined correlations with the Hospital Anxiety and Depression Scale (HADS), the Short Form Health Survey (SF-36), motor symptoms, genotype and disease duration.In this small patient sample, behavioural impairment was present in 29%of OPMD patients; in 17%the severity of symptoms was compatible with bvFTD. Correlations were small to medium.

Long-term follow-up in a cohort of children with isolated corpus callosum agenesis at fetal MRI.

OBJECTIVE: This long-term retrospective follow-up study aimed to address the knowledge gap between prenatal diagnosis of complete isolated Agenesis of Corpus Callosum (cACC) at fetal MRI and postnatal neurodevelopmental outcome to improve prenatal counseling for parents. METHODS: Data on fetuses with isolated cACC from a single-center MRI database built up in two decades were considered. Detailed postnatal clinical, neuropsychological evaluations were performed and descriptions of available neuroradiological and genetic data were provided. RESULTS: Following a detailed neuropsychological evaluation and a long-term follow-up, the subsequent results emerged: 38 school-aged children (older than 6 years) of 50 (aged 2.5-15 years) showed normal intellectual functions (50%), intellectual disability (21%), and borderline intelligence quotient (29%). Deficits in motor functions (58%), executive functions (37%), language (61%), memory abilities (58%), and academic performances (53%) were found. Twenty-one percent of participants showed behavioral difficulties. Almost half of the participants underwent rehabilitation. Additional findings (21%) were detected at postnatal brain MRI, and a significant association between additional findings at postnatal imaging and abnormal neurodevelopmental outcome was observed. INTERPRETATIONS: This study supports the view that children with prenatal diagnosis of isolated cACC may present with several degrees of neurologic and neuropsychological impairment which become more evident only in their second decade of life. Postnatal MRI and detailed genetic analysis may add crucial information to prenatal data and substantially influence final judgment on the outcome and orient clinical management and counseling.

The doll therapy as a first line treatment for behavioral and psychologic symptoms of dementia in nursing homes residents: a randomized, controlled study.

BACKGROUND: Patients living with dementia are severely affected by the development of behavioral and psychologic symptoms (BPSD) which represent a burden for patients and caregivers. The use of psychotropic drugs in the control of BPSD is widely diffused, however the use of a first line non-pharmacologic approach is highly recommended. Here we evaluate the effect of doll therapy (DT) in the management of BPSD, on the reduction of caregiver burden and delirium incidence in nursing home residents by a randomized controlled trial. METHODS: We enrolled fifty-two nursing homes residents living with dementia and BPSD. Subjects were randomized to DT (26) or standard treatment (ST, 26), we measured BPSD, caregiver burden and delirium with standard clinical scales at baseline, after 45 and 90 days. In order to evaluate the presence of BPSD we used Neuropsychiatric Inventory (NPI) scale and the A.Di.CO scale, the caregiver burden was measured by the Greutzner scale and delirium by the Confusion Assessment Method (CAM) scale. RESULTS: DT was more effective in reducing agitation and aggressiveness as respect to ST. Moreover DT globally reduced the presence of BPSD as dysphoria, wandering and apathy. We observed a significant reduction of the professional caregiver burden and the incidence of delirium was significantly reduced in subjects treated with DT. CONCLUSIONS: We show that DT is more effective that ST in the control of BSPD in patients affected by moderate to severe dementia. Moreover we suggest that DT may effective in reducing the incidence of delirium. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov the 10th June 2, 2021 trial registration number NCT04920591.

A Phase 3, Placebo-Controlled Trial of Once-Daily Viloxazine Extended-Release Capsules in Adolescents With Attention-Deficit/Hyperactivity Disorder.

PURPOSE: This phase 3 clinical trial evaluated the efficacy and safety of viloxazine extended-release capsules (VLX-ER) as a monotherapy for attention-deficit/hyperactivity disorder (ADHD) in adolescents (12-17 years). METHODS: Eligible subjects (n = 310) were randomized to receive once-daily 200 and 400 mg VLX-ER, or placebo for 6 weeks. The primary efficacy end point was change from baseline (CFB) at the end of study (EOS) in ADHD Rating Scale-5 Total score. Key secondary end points were Clinical Global Impression-Improvement score at EOS, CFB at EOS in Conners 3-Parent Short Form Composite T-score, and CFB at EOS in Weiss Functional Impairment Rating Scale-Parent Total average score. RESULTS: In the 200-mg/d and 400-mg/d VLX-ER treatment groups, a significant improvement was found in the CFB at EOS in ADHD Rating Scale-5 Total (P = 0.0232, P = 0.0091) and Inattention (P = 0.0424, P = 0.0390) and Hyperactivity/Impulsivity (P = 0.0069, P = 0.0005) subscale scores versus placebo. The Clinical Global Impression-Improvement score was significantly improved at EOS in the 200-mg/d and 400-mg/d VLX-ER groups versus placebo (P = 0.0042, P = 0.0003). The Conners 3-Parent Short Form composite T-score and Weiss Functional Impairment Rating Scale-Parent Total average score exhibited improvement in both VLX-ER groups; however, the difference versus placebo was not statistically significant. The most common treatment-related adverse events were somnolence, headache, decreased appetite, nausea, and fatigue. The adverse event-related discontinuation rates were <5% in all groups. CONCLUSIONS: Viloxazine extended-release demonstrated statistically significant and clinically meaningful improvement in ADHD symptoms in adolescents and was generally well tolerated.

Shorter Chain Triglycerides Are Negatively Associated with Symptom Improvement in Schizophrenia.

Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of the difference in treatment response observed among individuals with schizophrenia, and satisfactory markers of poor response are not available for clinical practice. Here, we studied the changes in the levels of 322 blood plasma lipids between two time points assessed in 92 individuals diagnosed with schizophrenia during their inpatient treatment and their association with the extent of symptom improvement. We found 20 triglyceride species increased in individuals with the least improvement in Positive and Negative Syndrome Scale (PANSS) scores, but not in those with the largest reduction in PANSS scores. These triglyceride species were distinct from the rest of the triglyceride species present in blood plasma. They contained a relatively low number of carbons in their fatty acid residues and were relatively low in abundance compared to the principal triglyceride species of blood plasma.

Time to Reconsider Monoamine Oxidase Inhibitors for Obsessive Compulsive Disorder?: A Case Series Using Phenelzine.

PURPOSE/BACKGROUND: Despite the availability of a range of efficacious evidence-based treatments for obsessive-compulsive disorder (OCD), not all patients experience sufficient benefit or are able to tolerate them in practice. Monoamine oxidase inhibitors (MAOIs) show efficacy in the treatment of depression and certain anxiety disorders (such as social anxiety disorder). METHODS/PROCEDURES: We survey the evidence base from case reports, and clinical trials, regarding use of MAOIs in OCD. We then present new data from a case series collected in routine clinical practice in a specialist clinical service. FINDINGS/RESULTS: In 9 treatment-resistant patients whose OCD had not improved with at least 2 standard treatment trials, 3 had marked clinical improvement (>35% improvement on YBOCS) on phenelzine, 3 had some improvement (15-34.9%), and 3 showed minimal or no improvement (<15%). In the 3 patients who experienced minimal/no improvement, 2 had discontinued early because of lack of tolerability, and the other patient discontinued after 4 weeks because of perceived lack of symptom benefit. IMPLICATIONS/CONCLUSIONS: We suggest that (1) MAOIs in treatment-resistant OCD require appropriate research scrutiny in large-scale randomized controlled trials; and (2) MAOIs merit consideration as a treatment option in individual cases of OCD, particularly in specialist settings where first-line interventions have proven inadequate to manage severe symptoms.