Severe mental illness: cardiovascular risk assessment and management.

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI.

Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK.

BACKGROUND: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). OBJECTIVE: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. METHODS: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. RESULTS: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label "death" was the top cause in the world (46 %) and in the UK (33 %). "Pneumonia" was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1-10 % of the UK clozapine fatal outcome number. CONCLUSIONS: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases.

Assessment and Diagnostic Classification Using DC:0-5 in Early Childhood Mental Health Clinics: The Protocol for the Developmental Psychiatry Diagnostic Challenges Study (DePsy).

Mental health problems in early childhood are common, but there is a lack of psychiatric research on this age group. DC:0-5 is a multiaxial classification system for mental disorders in early childhood, providing a framework for standardizing clinical practice and research. However, research on the validity of DC:0-5 is scarce. The Developmental Psychiatry Diagnostic Challenges Study (DePsy) is a multi-site, prospective clinical study including six German early childhood mental health (ECMH) clinics. The main objective of the study is to contribute to the validation of Axis I and Axis II of DC:0-5. A second aim of the study is to describe the population of the participating clinics regarding diagnoses, family context, and treatment outcomes. Additionally, the impact of environmental risk factors, including parental Adverse Childhood Experiences (ACEs) and media use, on child psychopathology and caregiver-child relationships will be examined. Over two years, patients aged 0.0-5.9 years old will be enrolled in the study. Assessments include ICD-10 and DC:0-5 diagnoses, developmental tests, video-based observations of caregiver-child interactions, and questionnaires on child psychopathology, media use, parental stress, and treatment satisfaction. Study results will promote the standardization of assessment and treatment in ECMH clinics aiming to improve the development of patients and their families.

Low availability, long wait times, and high geographic disparity of psychiatric outpatient care in the US.

OBJECTIVE: To identify potential barriers to care, this study examined the general psychiatry outpatient new appointment availability in the US, including in-person and telepsychiatry appointments, comparing results between insurance types (Medicaid vs. private insurance), states, and urbanization levels. METHOD: This mystery shopper study investigated 5 US states selected according to Mental Health America Adult Ranking and geography to represent the US mental health care system. Clinics across five selected states were stratified sampled by county urbanization levels. Calls were made during 05/2022-07/2022. Collected data included contact information accuracy, appointment availability, wait time (days), and related information. RESULTS: Altogether, 948 psychiatrists were sampled in New York, California, North Dakota, Virginia, and Wyoming. Overall contact information accuracy averaged 85.3%. Altogether, 18.5% of psychiatrists were available to see new patients with a significantly longer wait time for in-person than telepsychiatry appointments (median = 67.0 days vs median = 43.0 days, p < 0.01). The most frequent reason for unavailability was provider not taking new patients (53.9%). Mental health resources were unevenly distributed, favoring urban areas. CONCLUSION: Psychiatric care has been severely restricted in the US with low accessibility and long wait times. Transitioning to telepsychiatry represents a potential solution for rural disparities in access.

Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment.

OBJECTIVE: To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS). METHODS: Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking. RESULTS: We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93). CONCLUSION: Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).

Cost-effectiveness of a transdiagnostic psychotherapy program for youth with common mental health problems.

OBJECTIVES: Our objective was to evaluate the cost-effectiveness of the transdiagnostic psychotherapy program Mind My Mind (MMM) for youth with common mental health problems using a cost-utility analysis (CUA) framework and data from a randomized controlled trial. Furthermore, we analyzed the impact of the choice of informant for both quality-of-life reporting and preference weights on the Incremental Cost-Effectiveness Ratio (ICER). METHODS: A total of 396 school-aged (6-16 years) youth took part in the 6-month trial carried out in Denmark. CUAs were carried out for the trial period and four one-year extrapolation scenarios. Costs were based on a combination of budget and self-reported costs. Youths and parents were asked to report on the youth's quality-of-life three times during the trial using the Child Health Utility 9D (CHU9D). Parental-reported CHU9D was used in the base case together with preference weights of a youth population. Analyses using self-reported CHU9D and preference weights of an adult population were also carried out. RESULTS: The analysis of the trial period resulted in an ICER of €170,465. The analyses of the one-year scenarios resulted in ICERs between €23,653 and €50,480. The ICER increased by 24% and 71% compared to the base case when using self-reported CHU9D and adult preference weights, respectively. CONCLUSION: The MMM intervention has the potential to be cost-effective, but the ICER is dependent on the duration of the treatment effects. Results varied significantly with the choice of informant and the choice of preference weights indicating that both factors should be considered when assessing CUA involving youth.

Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Clozapine's multiple cellular mechanisms: What do we know after more than fifty years? A systematic review and critical assessment of translational mechanisms relevant for innovative strategies in treatment-resistant schizophrenia.

Almost fifty years after its first introduction into clinical care, clozapine remains the only evidence-based pharmacological option for treatment-resistant schizophrenia (TRS), which affects approximately 30% of patients with schizophrenia. Despite the long-time experience with clozapine, the specific mechanism of action (MOA) responsible for its superior efficacy among antipsychotics is still elusive, both at the receptor and intracellular signaling level. This systematic review is aimed at critically assessing the role and specific relevance of clozapine's multimodal actions, dissecting those mechanisms that under a translational perspective could shed light on molecular targets worth to be considered for further innovative antipsychotic development. In vivo and in vitro preclinical findings, supported by innovative techniques and methods, together with pharmacogenomic and in vivo functional studies, point to multiple and possibly overlapping MOAs. To better explore this crucial issue, the specific affinity for 5-HT2R, D1R, α2c, and muscarinic receptors, the relatively low occupancy at dopamine D2R, the interaction with receptor dimers, as well as the potential confounder effects resulting in biased ligand action, and lastly, the role of the moiety responsible for lipophilic and alkaline features of clozapine are highlighted. Finally, the role of transcription and protein changes at the synaptic level, and the possibility that clozapine can directly impact synaptic architecture are addressed. Although clozapine's exact MOAs that contribute to its unique efficacy and some of its severe adverse effects have not been fully understood, relevant information can be gleaned from recent mechanistic understandings that may help design much needed additional therapeutic strategies for TRS.

Development of a Symptom-Focused Model to Guide the Prescribing of Antipsychotics in Children and Adolescents: Results of the First Phase of the Safer Use of Antipsychotics in Youth (SUAY) Clinical Trial.

OBJECTIVE: To develop a new approach to prescribing guidelines as part of a pragmatic trial, Safer Use of Antipsychotics in Youth (SUAY; ClinicalTrials.gov Identifier: NCT03448575), which supports prescribers in delivering high-quality mental health care to youths. METHOD: A nominal group technique was used to identify first- to nth-line treatments for target symptoms and potential diagnoses. The panel included US pediatricians, child and adolescent psychiatrists, and psychopharmacology experts. Meeting materials included information about Medicaid review programs, systematic reviews, prescribing guidelines, and a description of the pragmatic trial. Afterward, a series of 4 webinar discussions were held to achieve consensus on recommendations. RESULTS: The panel unanimously agreed that the guideline should focus on target symptoms rather than diagnoses. Guidance included recommendations for first- to nth-line treatment of target mental health symptoms, environmental factors to be addressed, possible underlying diagnoses that should first be considered and ruled out, and general considerations for pharmacological and therapeutic treatments. CONCLUSION: Prescribing guidelines are often ignored because they do not incorporate the real-world availability of first-line psychosocial treatments, comorbid conditions, and clinical complexity. Our approach addresses some of these concerns. If the approach proves successful in our ongoing pragmatic trial, Safer Use of Antipsychotics in Youth (SUAY), it may serve as a model to state Medicaid programs and health systems to support clinicians in delivering high-quality mental health care to youths. CLINICAL TRIAL REGISTRATION INFORMATION: Safer Use of Antipsychotics in Youth; http://clinicaltrials.gov/; NCT03448575.

Validity of the Aktibipo Self-rating Questionnaire for the Digital Self-assessment of Mood and Relapse Detection in Patients With Bipolar Disorder: Instrument Validation Study.

BACKGROUND: Self-reported mood is a valuable clinical data source regarding disease state and course in patients with mood disorders. However, validated, quick, and scalable digital self-report measures that can also detect relapse are still not available for clinical care. OBJECTIVE: In this study, we aim to validate the newly developed ASERT (Aktibipo Self-rating) questionnaire-a 10-item, mobile app-based, self-report mood questionnaire consisting of 4 depression, 4 mania, and 2 nonspecific symptom items, each with 5 possible answers. The validation data set is a subset of the ongoing observational longitudinal AKTIBIPO400 study for the long-term monitoring of mood and activity (via actigraphy) in patients with bipolar disorder (BD). Patients with confirmed BD are included and monitored with weekly ASERT questionnaires and monthly clinical scales (Montgomery-Åsberg Depression Rating Scale [MADRS] and Young Mania Rating Scale [YMRS]). METHODS: The content validity of the ASERT questionnaire was assessed using principal component analysis, and the Cronbach α was used to assess the internal consistency of each factor. The convergent validity of the depressive or manic items of the ASERT questionnaire with the MADRS and YMRS, respectively, was assessed using a linear mixed-effects model and linear correlation analyses. In addition, we investigated the capability of the ASERT questionnaire to distinguish relapse (YMRS≥15 and MADRS≥15) from a nonrelapse (interepisode) state (YMRS<15 and MADRS<15) using a logistic mixed-effects model. RESULTS: A total of 99 patients with BD were included in this study (follow-up: mean 754 days, SD 266) and completed an average of 78.1% (SD 18.3%) of the requested ASERT assessments (completion time for the 10 ASERT questions: median 24.0 seconds) across all patients in this study. The ASERT depression items were highly associated with MADRS total scores (P<.001; bootstrap). Similarly, ASERT mania items were highly associated with YMRS total scores (P<.001; bootstrap). Furthermore, the logistic mixed-effects regression model for scale-based relapse detection showed high detection accuracy in a repeated holdout validation for both depression (accuracy=85%; sensitivity=69.9%; specificity=88.4%; area under the receiver operating characteristic curve=0.880) and mania (accuracy=87.5%; sensitivity=64.9%; specificity=89.9%; area under the receiver operating characteristic curve=0.844). CONCLUSIONS: The ASERT questionnaire is a quick and acceptable mood monitoring tool that is administered via a smartphone app. The questionnaire has a good capability to detect the worsening of clinical symptoms in a long-term monitoring scenario.

Socio-economic position as a moderator of cardiometabolic outcomes in patients receiving psychotropic treatment associated with weight gain: results from a prospective 12-month inception cohort study and a large population-based cohort.

Weight gain and metabolic complications are major adverse effects of many psychotropic drugs. We aimed to understand how socio-economic status (SES), defined as the Swiss socio-economic position (SSEP), is associated with cardiometabolic parameters after initiation of psychotropic medications known to induce weight gain. Cardiometabolic parameters were collected in two Swiss cohorts following the prescription of psychotropic medications. The SSEP integrated neighborhood-based income, education, occupation, and housing condition. The results were then validated in an independent replication sample (UKBiobank), using educational attainment (EA) as a proxy for SES. Adult patients with a low SSEP had a higher risk of developing metabolic syndrome over one year versus patients with a high SSEP (Hazard ratio (95% CI) = 3.1 (1.5-6.5), n = 366). During the first 6 months of follow-up, a significant negative association between SSEP and body mass index (BMI), weight change, and waist circumference change was observed (25 ≤ age < 65, n = 526), which was particularly important in adults receiving medications with the highest risk of weight gain, with a BMI difference of 0.86 kg/m2 between patients with low versus high SSEP (95% CI: 0.03-1.70, n = 99). Eventually, a causal effect of EA on BMI was revealed using Mendelian randomization in the UKBiobank, which was notably strong in high-risk medication users (beta: -0.47 SD EA per 1 SD BMI; 95% CI: -0.46 to -0.27, n = 11,314). An additional aspect of personalized medicine was highlighted, suggesting the patients' SES represents a significant risk factor. Particular attention should be paid to patients with low SES when initiating high cardiometabolic risk psychotropic medications.

Preventive psychiatry: a blueprint for improving the mental health of young people.

Preventive approaches have latterly gained traction for improving mental health in young people. In this paper, we first appraise the conceptual foundations of preventive psychiatry, encompassing the public health, Gordon's, US Institute of Medicine, World Health Organization, and good mental health frameworks, and neurodevelopmentally-sensitive clinical staging models. We then review the evidence supporting primary prevention of psychotic, bipolar and common mental disorders and promotion of good mental health as potential transformative strategies to reduce the incidence of these disorders in young people. Within indicated approaches, the clinical high-risk for psychosis paradigm has received the most empirical validation, while clinical high-risk states for bipolar and common mental disorders are increasingly becoming a focus of attention. Selective approaches have mostly targeted familial vulnerability and non-genetic risk exposures. Selective screening and psychological/psychoeducational interventions in vulnerable subgroups may improve anxiety/depressive symptoms, but their efficacy in reducing the incidence of psychotic/bipolar/common mental disorders is unproven. Selective physical exercise may reduce the incidence of anxiety disorders. Universal psychological/psychoeducational interventions may improve anxiety symptoms but not prevent depressive/anxiety disorders, while universal physical exercise may reduce the incidence of anxiety disorders. Universal public health approaches targeting school climate or social determinants (demographic, economic, neighbourhood, environmental, social/cultural) of mental disorders hold the greatest potential for reducing the risk profile of the population as a whole. The approach to promotion of good mental health is currently fragmented. We leverage the knowledge gained from the review to develop a blueprint for future research and practice of preventive psychiatry in young people: integrating universal and targeted frameworks; advancing multivariable, transdiagnostic, multi-endpoint epidemiological knowledge; synergically preventing common and infrequent mental disorders; preventing physical and mental health burden together; implementing stratified/personalized prognosis; establishing evidence-based preventive interventions; developing an ethical framework, improving prevention through education/training; consolidating the cost-effectiveness of preventive psychiatry; and decreasing inequalities. These goals can only be achieved through an urgent individual, societal, and global level response, which promotes a vigorous collaboration across scientific, health care, societal and governmental sectors for implementing preventive psychiatry, as much is at stake for young people with or at risk for emerging mental disorders.

The need for holistic, longitudinal and comparable, real-time assessment of the emotional, behavioral and societal impact of the COVID-19 pandemic across nations.

As of the end of 2020, the COVID-19 pandemic has led to over 82 million verified infections and almost 1.8 million COVID-19-related deaths worldwide,1 resulting to an unprecedented public health response around the globe. The COVID-19 pandemic, together with the applied multi-level restrictive measures, has generated a unique combination of an unpredictable and stressful biomedical and socioeconomic environment (i.e., syndemic),2 introducing real-life threat, involuntary and drastic every-day life-style changes with uncertain financial and future prospects, alongside with minimized coping and stress management possibilities.3 This combination of so many different and vital stressors may lead to acute as well as long-term, direct, indirect and even transgenerational unfavourable effects on physical and mental health and functioning, which might even represent the most precarious and still unpredictable public-health-related part of the pandemic.4 Thereby, specific population groups could be at particular risk of poor health outcomes in relation to applied public health measures.4, 5 However, not every individual will experience the same level of negative impact on health and well-being during the pandemic, as several additional national, socioeconomic, environmental, behavioural, emotional and cognitive factors can moderate individual resilience and coping.6 Pandemic-related research should, thus, assess as many multidimensional risk and protective factors as possible in a longitudinal, large-scale and multi-national manner, enabling a profound and comprehensive understanding of the complex health and societal impact of the pandemic worldwide.7 Nevertheless, to date, most research findings are cross-sectional, report on small and non- representative samples from individual countries, or on specific population groups (e.g., health care workers, students, clinical populations) and usually assess only a very restricted set of outcomes and time-points. Thereby, only few studies assess coping strategies, medical history or detailed socioeconomic, demographic and environmental data. In addition, most studies leave behind linguistic differences, being available in one or at best two different languages. Such investigations of small outcome subsets within a narrow framework preclude a broader and clear understanding of the multifaceted pandemic impact on the general population and specific subgroups. Acknowledging these gaps in the existing literature, large- scale, collaborative research prospectively collecting and monitoring a broad range of real- time, multi-dimensional health-related, societal and behavioural outcome data from countries across the globe is currently explicitly needed. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH- FIT) envisions to fill this gap. Based on an easy-to-access webpage (www.coh-fit.com), COH- FIT is the currently largest-scale known international collaborative study of over 200 researchers around the globe, prospectively collecting the biggest set of multi-dimensional and multi-disciplinary data from 150 high, middle, and low-income countries in over 30 languages and in three different age groups (adults, adolescents, children) of the general population, focusing also on relevant at-risk subgroups. Albeit being a cross-sectional anonymous survey on an individual level, it is a longitudinal study on a population level, as data are collected continuously since April 2020 and until the WHO declares the end of the pandemic. In addition to snowball recruitment, this project also collects information from nationally representative samples. Furthermore, COH-FIT is the first study of this scale investigating pandemic effects on health and functioning measures between family members, while it also specifically assesses a large list of behavioral and coping factors (e.g., screen time, social media usage, physical activity, social interaction, religious practices, etc.) on outcomes of interest. COH-FIT also monitors changes in public health restrictive measures to enhance data harmonization across nations and time, and to better investigate their impact on physical and mental health, while it also collects information on changes in healthcare systems functioning. The COH-FIT project was worldwide first initiated in Greece after the ethics committee approval of the School of Medicine of the Aristotle University of Thessaloniki and is officially supported by the Hellenic Psychiatric Association, European Psychiatric Association, World Association of Social Psychiatry, ECNP Network on the Prevention of Mental Disorders and Mental Health Promotion, among many other national and international scientific associations. To date, COH-FIT has already collected >115,000 participations worldwide (>8,000 in Greece), but more participants are still needed, both during the second and third wave of the pandemic, as in the future, after the pandemic has ended. Currently, the COH-FIT survey actively collects the largest sample on multifactorial data on the impact of the COVD-19 pandemic on health and functioning not only in Greece, but around the globe. The elaborated design of COH-FIT and similar studies may allow a better identification of key parameters and population groups at increased risk during the pandemic, as well as potential targets for acute and long-term prevention or intervention strategies in the current as in possible future pandemics. A profound understanding of the health and societal impact of the pandemic could facilitate an optimized governmental, social and individual health preparedness during infection times8 and the bridging of individuals', societal and systemic needs and actions through multi-level guideline development with the aim to improve mental health outcomes globally.

Expanding phenomenologic heterogeneity of tardive syndromes: Time for an updated assessment tool.

Tardive syndromes (TDS) are a group of hyperkinetic and hypokinetic movement disorders that occurs after exposure to dopamine receptor blocking agents such as antipsychotic and antiemetic drugs. The Abnormal Involuntary Movement Scale (AIMS) is a widely used instrument that has become the standard for assessment of tardive dyskinesia (TDD), the most common form of TDS. However, the AIMS has a number of clinimetric limitations and was designed primarily to assess the anatomic distribution and severity of involuntary movements without regard to phenomenology. To build on recent advances in understanding and treatment of TDS, re-evaluation and revision of the AIMS that could aid both clinical practice and research may be worthwhile. Challenges, such as retaining the efficiency of the current AIMS, incorporating evaluation of impairment in daily activities, and re-training clinicians for a revised examination procedure and rating instrument, are very likely surmountable.

Using Patient-Centered Assessment in Schizophrenia Care: Defining Recovery and Discussing Concerns and Preferences.

Syndromal recovery, satisfactory quality of life, and adequate functionality are relevant goals that define successful treatment of schizophrenia. Recovery requires effective symptom control in multiple clinical domains but also sufficient self-care and social and educational/vocational functionality. The finding that residual negative and cognitive symptoms have been related strongly to inadequate levels of functioning in people with schizophrenia is related to the fact that current pharmacologic agents tend to be most effective for the positive symptoms of the disease. Additional challenges include psychiatric comorbidities and adverse events related to medication that can lead to secondary negative and cognitive symptoms and nonadherence, all of which can worsen outcomes. Treatment modalities that target cognition and functional rehabilitation without introducing tolerability issues are needed. In general, pharmacologic interventions should be combined with evidence-based nonpharmacologic treatments, and patient-reported outcomes as well as measurement-based care should be employed, ideally in a coordinated specialty care framework. To facilitate positive treatment decisions, a combined shared decision and motivational interviewing approach should be implemented.

Assessment of Physical Activity Patterns in Adolescent Patients with Anorexia Nervosa and Their Effect on Weight Gain.

(1) Background: Altered physical activity (PA) affects weight recovery in anorexia nervosa (AN) patients. The study aimed to objectively characterize PA patterns and their effect on weight trajectory in adolescent AN patients. (2) Methods: PA was assessed in 47 patients on admission to inpatient treatment, in n = 25 of these patients again 4 weeks after discharge (follow-up, FU), as well as in 20 adolescent healthy controls using the Sense Wear™ armband. The following PA categories were defined by metabolic equivalent (MET) ranges: sedentary behavior (SB), light (LPA), moderate (MPA), vigorous (VPA), and high-level PA (HLPA= MPA + VPA). (3) Results: LPA on admission was significantly higher in AN patients than in controls (103 vs. 55 min/d, p < 0.001), and LPA in AN decreased over time to 90 min/d (p = 0.006). Patients with higher admission LPA (n = 12) still had elevated LPA at FU (p = 0.003). High admission LPA was associated with a higher inpatient BMI percentage gain (ΔBMI%; 18.2% ± 10.0% vs. 12.0% ± 9.7%, p = 0.037) but with a loss of ΔBMI% at FU (-2.3% ± 3.6% vs. 0.8% ± 3.6%, p = 0.045). HLPA at baseline was associated with a lower inpatient ΔBMI% (p = 0.045). (4) Conclusion: Elevated LPA in AN patients decreased after inpatient treatment, and PA patterns had an impact on weight trajectory.

Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment.

Schizophrenia is frequently a chronic and disabling disorder, characterized by heterogeneous positive and negative symptom constellations. The objective of this review was to provide information that may be useful for clinicians treating patients with negative symptoms of schizophrenia. Negative symptoms are a core component of schizophrenia that account for a large part of the long-term disability and poor functional outcomes in patients with the disorder. The term negative symptoms describes a lessening or absence of normal behaviors and functions related to motivation and interest, or verbal/emotional expression. The negative symptom domain consists of five key constructs: blunted affect, alogia (reduction in quantity of words spoken), avolition (reduced goal-directed activity due to decreased motivation), asociality, and anhedonia (reduced experience of pleasure). Negative symptoms are common in schizophrenia; up to 60% of patients may have prominent clinically relevant negative symptoms that require treatment. Negative symptoms can occur at any point in the course of illness, although they are reported as the most common first symptom of schizophrenia. Negative symptoms can be primary symptoms, which are intrinsic to the underlying pathophysiology of schizophrenia, or secondary symptoms that are related to psychiatric or medical comorbidities, adverse effects of treatment, or environmental factors. While secondary negative symptoms can improve as a consequence of treatment to improve symptoms in other domains (ie, positive symptoms, depressive symptoms or extrapyramidal symptoms), primary negative symptoms generally do not respond well to currently available antipsychotic treatment with dopamine D2 antagonists or partial D2 agonists. Since some patients may lack insight about the presence of negative symptoms, these are generally not the reason that patients seek clinical care, and clinicians should be especially vigilant for their presence. Negative symptoms clearly constitute an unmet medical need in schizophrenia, and new and effective treatments are urgently needed.

The use of long-acting Aripiprazole in a multi-center, prospective, uncontrolled, open-label, cohort study in Germany: a report on global assessment of functioning and the WHO wellbeing index.

BACKGROUND: In this non-interventional study, the functionality and well-being of patients with schizophrenia with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic population. METHODS: This non-interventional, prospective, multicenter 6-month study included 242 predominantly symptomatically stable patients (mean age 43.1 ± 15.1 years, 55% male) who switched their treatment to AOM after 9.7 (± 22.3) months of oral treatment. Outcome parameters included functionality (Global Assessment of Functioning, GAF), patient's wellbeing (WHO-5 Well-Being Index, WHO-5), and both patient's and clinician's assessment of efficacy and tolerability of AOM. Treatment emergent adverse events (TRAE) were also recorded. RESULTS: At baseline, the mean GAF score was 47.0 (±13.9), indicating that patients experienced serious impairment in functioning. A continuous increase to 60.2 (±17.0) during treatment was found, with a robust and significant increase already after 4 weeks. At study start, patients reported diminished wellbeing, with a mean score of 10.6 (±5.6) on the WHO-5 scale. During treatment, patient wellbeing increased continuously with strong and significant improvements even after 4 weeks and an overall improvement of 4.8 (±6.9) over the course of 6 months with an endpoint of 15.4 (±5.5). Stratification of these results showed that more pronounced effects were achieved in younger patients ≤35 years (p<0.05 for GAF). The effectiveness and tolerability of AOM was rated good/very good by most patients (89.2 and 93.7%) and physicians (91.4 and 96.8%). Only few TRAEs occurred. CONCLUSIONS: Our results show a significant positive effect after initiation of AOM treatment in predominantly stable patients with schizophrenia on their functioning and wellbeing, which was even more pronounced in patients aged ≤35 years, thereby supporting previous randomized controlled findings under routine conditions in clinical practice.

Metabolic Monitoring Rates of Youth Treated with Second-Generation Antipsychotics in Usual Care: Results of a Large US National Commercial Health Plan.

Objectives: To examine metabolic monitoring rates in commercially insured children and adolescents treated with a second-generation antipsychotic (SGA) during calendar years (CYs) 2016 and 2017. Methods: In this retrospective study, data were collected from a large national commercial health plan for the period covering January 1, 2016 to December 31, 2017. Commercially insured children and adolescents, aged 8-19 years with ≥2 SGA prescription claims during the CY, were identified for the CY2016 and CY2017 cohorts. The primary outcome of interest was the percentage of subjects with any glucose or lipid metabolism parameter monitoring. Other calculated metabolic testing rates included glucose, hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), other cholesterol (including triglycerides), and combined glucose and lipid metabolism testing (≥1 test for blood glucose or HbA1c and ≥1 test for LDL-C or other cholesterol). Results: In CY2016 and CY2017, 1502 and 1239 subjects, respectively, were identified for this study. The most common psychiatric diagnoses in CY2016 and CY2017 were major depressive disorder (57.1%, 56.5%, respectively), anxiety disorders (42.9%, 47.5%), attention-deficit/hyperactivity disorder (41.6%, 45.8%), and bipolar disorder (24.1%, 25.9%). The rate of any metabolic testing was 53.5% in CY2016 and 51.3% in CY2017. Glucose testing (50.3%, 46.9%, respectively) was most common in both CYs, followed by LDL-C testing (31.2%, 28.5%). Rates of combined glucose and lipid metabolism testing were 30.7% in CY2016 and 26.9% in CY2017. Conclusions: Given the known potential for adverse cardiometabolic effects, rates of metabolic monitoring associated with SGA use in children and adolescents urgently need to be improved. There is a critical need for understanding barriers to routine monitoring, particularly of lipids, and developing interventions to enhance metabolic monitoring.