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Competing Interests: Dr. Chengappa is listed as a co-inventor on a patent assigned to the University of Pittsburgh. Dr. Cotes has received research funding (to his institution) from Alkermes, Karuna, and Otsuka, and he has served as a speaker and consultant for Saladax Biomedical and as a speaker for Clinical Care Options.

During the postcrisis period, many individuals struggle to transition to available care, often falling through the cracks. This article discusses effective postcrisis approaches that provide rapid access to transitional team-based care using critical time intervention strategies. It also highlights the development of state, county, and funder models for "care-traffic control" to ensure swift linkage to follow-up services, along with new funding models that support intensive community crisis stabilization during the postcrisis period. Emerging crisis systems can leverage these emerging services and approaches to facilitate successful transitions for individuals in need., Competing Interests: Disclosure Outside of this work, Dr R.O. Cotes has received research funding from Alkermes, Ireland, Karuna, Otsuka, Japan, and Roche, Switzerland. He is a consultant to the American Psychiatric Association and Saladax Biomedical, and a speaker for Clinical Care Options. The remaining authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Research on automated mental health assessment tools has been growing in recent years, often aiming to address the subjectivity and bias that existed in the current clinical practice of the psychiatric evaluation process. Despite the substantial health and economic ramifications, the potential unfairness of those automated tools was understudied and required more attention. In this work, we systematically evaluated the fairness level in a multimodal remote mental health dataset and an assessment system, where we compared the fairness level in race, gender, education level, and age. Demographic parity ratio (DPR) and equalized odds ratio (EOR) of classifiers using different modalities were compared, along with the F1 scores in different demographic groups. Post-training classifier threshold optimization was employed to mitigate the unfairness. No statistically significant unfairness was found in the composition of the dataset. Varying degrees of unfairness were identified among modalities, with no single modality consistently demonstrating better fairness across all demographic variables. Post-training mitigation effectively improved both DPR and EOR metrics at the expense of a decrease in F1 scores. Addressing and mitigating unfairness in these automated tools are essential steps in fostering trust among clinicians, gaining deeper insights into their use cases, and facilitating their appropriate utilization., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Psychiatric evaluation suffers from subjectivity and bias, and is hard to scale due to intensive professional training requirements. In this work, we investigated whether behavioral and physiological signals, extracted from tele-video interviews, differ in individuals with psychiatric disorders., Methods: Temporal variations in facial expression, vocal expression, linguistic expression, and cardiovascular modulation were extracted from simultaneously recorded audio and video of remote interviews. Averages, standard deviations, and Markovian process-derived statistics of these features were computed from 73 subjects. Four binary classification tasks were defined: detecting 1) any clinically-diagnosed psychiatric disorder, 2) major depressive disorder, 3) self-rated depression, and 4) self-rated anxiety. Each modality was evaluated individually and in combination., Results: Statistically significant feature differences were found between psychiatric and control subjects. Correlations were found between features and self-rated depression and anxiety scores. Heart rate dynamics provided the best unimodal performance with areas under the receiver-operator curve (AUROCs) of 0.68-0.75 (depending on the classification task). Combining multiple modalities provided AUROCs of 0.72-0.82., Conclusion: Multimodal features extracted from remote interviews revealed informative characteristics of clinically diagnosed and self-rated mental health status., Significance: The proposed multimodal approach has the potential to facilitate scalable, remote, and low-cost assessment for low-burden automated mental health services.

Background: Automatic speech recognition (ASR) technology is increasingly being used for transcription in clinical contexts. Although there are numerous transcription services using ASR, few studies have compared the word error rate (WER) between different transcription services among different diagnostic groups in a mental health setting. There has also been little research into the types of words ASR transcriptions mistakenly generate or omit., Objective: This study compared the WER of 3 ASR transcription services (Amazon Transcribe [Amazon.com, Inc], Zoom-Otter AI [Zoom Video Communications, Inc], and Whisper [OpenAI Inc]) in interviews across 2 different clinical categories (controls and participants experiencing a variety of mental health conditions). These ASR transcription services were also compared with a commercial human transcription service, Rev (Rev.Com, Inc). Words that were either included or excluded by the error in the transcripts were systematically analyzed by their Linguistic Inquiry and Word Count categories., Methods: Participants completed a 1-time research psychiatric interview, which was recorded on a secure server. Transcriptions created by the research team were used as the gold standard from which WER was calculated. The interviewees were categorized into either the control group (n=18) or the mental health condition group (n=47) using the Mini-International Neuropsychiatric Interview. The total sample included 65 participants. Brunner-Munzel tests were used for comparing independent sets, such as the diagnostic groupings, and Wilcoxon signed rank tests were used for correlated samples when comparing the total sample between different transcription services., Results: There were significant differences between each ASR transcription service's WER (P<.001). Amazon Transcribe's output exhibited significantly lower WERs compared with the Zoom-Otter AI's and Whisper's ASR. ASR performances did not significantly differ across the 2 different clinical categories within each service (P>.05). A comparison between the human transcription service output from Rev and the best-performing ASR (Amazon Transcribe) demonstrated a significant difference (P<.001), with Rev having a slightly lower median WER (7.6%, IQR 5.4%-11.35 vs 8.9%, IQR 6.9%-11.6%). Heat maps and spider plots were used to visualize the most common errors in Linguistic Inquiry and Word Count categories, which were found to be within 3 overarching categories: Conversation, Cognition, and Function., Conclusions: Overall, consistent with previous literature, our results suggest that the WER between manual and automated transcription services may be narrowing as ASR services advance. These advances, coupled with decreased cost and time in receiving transcriptions, may make ASR transcriptions a more viable option within health care settings. However, more research is required to determine if errors in specific types of words impact the analysis and usability of these transcriptions, particularly for specific applications and in a variety of populations in terms of clinical diagnosis, literacy level, accent, and cultural origin., (©Salman Seyedi, Emily Griner, Lisette Corbin, Zifan Jiang, Kailey Roberts, Luca Iacobelli, Aaron Milloy, Mina Boazak, Ali Bahrami Rad, Ahmed Abbasi, Robert O Cotes, Gari D Clifford. Originally published in JMIR Mental Health (https://mental.jmir.org), 31.10.2023.)

The objective was to determine the feasibility of an Open Dialogue-inspired approach in a metropolitan, public hospital setting with predominately African American participants. Participants were ages 18-35, experienced psychosis within the past month, and involved at least one support person in their care. We evaluated domains of feasibility including implementation, adaptation, practicality, acceptability, and limited-efficacy. An organizational change model (Addressing Problems Through Organizational Change) facilitated implementation. Clinicians received three trainings and ongoing supervision. Network meetings were successfully implemented with good self-reported fidelity to principles of dialogic practice. Some adaptations (less frequent meetings and no home visits) were necessary. A subset of individuals completed research assessments over 12 months. Qualitative interviews with participants suggested the intervention was acceptable. Symptom and functional outcomes were preliminary but trended toward improvement. Implementation was feasible with relatively brief training, organizational change processes, and context-specific adaptations. Lessons learned can assist in planning a larger research study., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Treatment-resistant symptoms occur in about a third of patients with schizophrenia and are associated with a substantial reduction in their quality of life. The development of new treatment options for clozapine-resistant schizophrenia constitutes a crucial, unmet need in psychiatry. Additionally, an overview of past and possible future research avenues to optimise the early detection, diagnosis, and management of clozapine-resistant schizophrenia is unavailable. In this Health Policy, we discuss the ongoing challenges associated with clozapine-resistant schizophrenia faced by patients and health-care providers worldwide to improve the understanding of this condition. We then revisit several clozapine guidelines, the diagnostic tests and treatment options for clozapine-resistant schizophrenia, and currently applied research approaches in clozapine-resistant schizophrenia. We also suggest methodologies and targets for future research, divided into innovative nosology-oriented field trials (eg, examining dimensional symptom staging), translational approaches (eg, genetics), epidemiological research (eg, real-world studies), and interventional studies (eg, non-traditional trial designs incorporating lived experiences and caregivers' perspectives). Finally, we note that low-income and middle-income countries are under-represented in studies on clozapine-resistant schizophrenia and propose an agenda to guide multinational research on the cause and treatment of clozapine-resistant schizophrenia. We hope that this research agenda will empower better global representation of patients living with clozapine-resistant schizophrenia and ultimately improve their functional outcomes and quality of life., Competing Interests: Declaration of interests JL has received honoraria from Otsuka, Janssen, Lundbeck, and Sumitomo Pharmaceuticals. CUC has been a consultant or advisor to, or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen (Johnson & Johnson), Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He has provided expert testimony for Janssen and Otsuka. He has served on a data safety monitoring board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He has received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic. ROC has received research funding (awarded to his institution) from Roche and Alkermes, is a consultant to Saladax Biomedical, and is a speaker for Clinical Care Options. ST has received speaker honoraria from Otsuka, Mochida, Takeda, Meiji, Eisai, Sumitomo, Viatris, and Teijin. JT has participated in research projects funded by grants from Janssen-Cilag and Eli Lilly awarded to his institution. He also reports personal fees from Eli Lilly, Evidera, Janssen-Cilag, Lundbeck, Mediuutiset, Otsuka, Sidera, and Suvovion; and he is a consultant to HLS Therapeutics, Orion, and WebMed Global. AH is co-editor of the German Association for Psychiatry, Psychotherapy and Psychosomatics schizophrenia treatment guidelines and first author of the World Federation of Societies of Biological Psychiatry schizophrenia treatment guidelines. He has been on the advisory boards and has received speaker fees from Janssen, Lundbeck, and Otsuka. EW has been on the advisory boards of Recordati. JMG-D is funded by a grant from Ministerio de Ciencia y Tecnología (Colombia), and has been a consultant for, received honoraria from, or been on the speakers or advisory boards of Janssen, Eurofarma, Servier, Sanofi, Lilly, and Pfizer. DSh is an expert advisor to the National Institute for Health and Care Excellence (NICE) centre for guidelines; the views expressed in this Health Policy are the authors' and not those of NICE. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose/background: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis., Methods: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions., Findings/results: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year., Implications/conclusions: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Clozapine is the most efficacious antipsychotic medication, but it is underutilized and its mechanism of action is still poorly understood. One aspect of its unique efficacy that requires further study is its effect on suicidality. A randomized controlled trial, the InterSePT study, yielded evidence that clozapine reduces suicidality more than olanzapine, after which it became the only medication indicated for recurrent suicidal behavior in schizophrenia and schizoaffective disorder. We present here the first study of population mortality data to investigate the effect of clozapine on suicide., Methods: We reviewed statewide autopsy records of Maryland's Office of the Chief Medical Examiner, which performs uniquely comprehensive death investigations that include full toxicologic panels with postmortem blood levels of antipsychotics. Our study compared clozapine- and olanzapine-positive decedents across demographic, clinical, and manner-of-death outcomes using contingency table analysis and logistic regression., Results: Of 53,144 decedents from 2003 to 2021, 621 had clozapine or olanzapine detected on autopsy, with the two groups showing no demographic differences. Decedents with clozapine were significantly less likely to have died by suicide than by accident compared to those with olanzapine (odds ratio = 0.47; 95% CI, 0.26-0.84; P  = .011)., Conclusions: Our study thus adds more naturalistic evidence to the growing literature on the beneficial effect of clozapine on suicidality. Our findings also highlight the utility of statewide autopsy records, an untapped resource for investigating the potential protective effect of psychiatric medications on suicide at a population level., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Objectives: An international guideline recently provided certain personalized schedules for titrating clozapine in adult inpatients by considering: 1) DNA ancestry group, 2) sexsmoking subgroup, and 3) presence/absence of clozapine poor metabolizer (PM) status. Measuring CRP levels at baseline and during the first 4 weeks is recommended. Titrations too fast for the metabolism of specific patients can lead to clozapine-induced inflammations and CRP elevations. Methods: Three published cases are reinterpreted. Better outcomes might have been obtained by using the guideline. Results: Case 1 was a Chinese male non-smoker, a clozapine PM due to an underlying inflammation. Case 2 was a Turkish female non-smoker who developed clozapine-induced myocarditis in the context of 4 risk factors (undiagnosed infl ammation, obesity, valproate and olanzapine co-prescription). Case 3 was a United States patient of European ancestry with no known risk factors who developed myocarditis after a routine titration and had an unsuccessful rechallenge with 12.5 mg/day. Application of the international clozapine titration guideline may have prevented: 1) Case 1 by recommending against clozapine titration for a patient with an abnormal CRP level, 2) Case 2 by considering 4 risk factors and using a slow titration for clozapine PMs, and 3) Case 3 by using CRP elevations for early identification of a possible genetic PM. Conclusions: When baseline or prior CRPs are normal and then become abnormal during a clozapine titration, this indicates: 1) clozapine-induced inflammation associated with too-rapid titration for that specific patient, and/or 2) co-occurrence of an infection. Prospective studies need to verify this hypothesis., ((Neuropsychopharmacol Hung 2022; 24(4): 153–161).)

Purpose: Although clozapine was Food and Drug Administration (FDA) approved more than 3 decades ago, major barriers and gaps in knowledge continue to prevent its effective and safe use. We review modern-day problems encountered with clozapine in the United States (US)., Methods: Information surrounding current administrative, clinical, research, and technological gaps or barriers related to clozapine use in the US was reviewed., Findings: The history of how clozapine became FDA approved likely contributes to gaps in knowledge. The frequency of safety warnings added to the FDA prescribing information may add to fears about clozapine, as evidence by numerous published survey studies. The clozapine Risk Evaluation and Mitigation Strategy (REMS) program has been modified several times in the last decade, causing access and safety issues for patients, which are discussed. Evidence may suggest that the FDA REMS requirements for hematologic monitoring are too cumbersome, and there may be ability to safely loosen requirements. The COVID-19 pandemic brought forth the ability for extended interval monitoring but also greater awareness of the clozapine-inflammation interaction. Newer guidelines published describe considerations in personalizing clozapine titration based on principles of ethnopsychopharmacology. Emerging technologies to support the use of clozapine are not widely available., Implications: Clozapine is a unique life-saving drug but it is underused in the US, despite its established efficacy. The 2021 REMS changes led to significant difficulties for providers and patients. We highlight the importance of the clozapine-inflammation interaction, therapeutic drug monitoring, and the ability for individual care based on patient-specific factors. There is an urgent need for advancing technology used for clozapine monitoring, evaluating barriers created by REMS, and establishing consistent practices throughout the US., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with mental disorders are at increased risk of premature mortality. Psychiatric inpatients are a particularly vulnerable population, yet data on the mortality rate and causes of death among psychiatric inpatients in a national sample are scarce., Methods: We analyzed data collected from patients who died during psychiatric hospitalization in 2019 and 2020 from 41 psychiatric hospitals in China., Results: In total, 719 inpatients died over the study period. There were more deaths in 2019 (N = 409, 56.9%) compared to 2020 (N = 310, 43.1%). The mean age was 73.3 ± 16.5 years old, with males significantly younger than females (71.5 ± 16.9 vs. 75.9 ± 15.6, p < 0.001). Sudden death accounted for 11.5% of all deaths. The cause was unknown for 31.2% of cases. Among those with known causes of death, respiratory disorders were most common in patients with psychotic disorders (41.9%) and mood disorders (29.8%). Suicide accounted for 17.0% of deaths in patients with mood disorders., Conclusion: Patients who died during psychiatric hospitalization were overall older (>70 years), and more than one in ten died due to sudden death. While respiratory disorders accounted for the largest proportion of known causes, the causes were unknown in nearly one-third. Death due to suicide, a preventable cause, remained common among patients with mood disorders. Evidence-based interventions should be implemented., Competing Interests: Conflicts of Interest Dr. Yi-lang Tang receives research funding from the U.S. Department of Veterans Administration for a medication clinical trial. The authors declare that there are no conflicts involved in the article., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Current standards of psychiatric assessment and diagnostic evaluation rely primarily on the clinical subjective interpretation of a patient's outward manifestations of their internal state. While psychometric tools can help to evaluate these behaviors more systematically, the tools still rely on the clinician's interpretation of what are frequently nuanced speech and behavior patterns. With advances in computing power, increased availability of clinical data, and improving resolution of recording and sensor hardware (including acoustic, video, accelerometer, infrared, and other modalities), researchers have begun to demonstrate the feasibility of cutting-edge technologies in aiding the assessment of psychiatric disorders., Objective: We present a research protocol that utilizes facial expression, eye gaze, voice and speech, locomotor, heart rate, and electroencephalography monitoring to assess schizophrenia symptoms and to distinguish patients with schizophrenia from those with other psychiatric disorders and control subjects., Methods: We plan to recruit three outpatient groups: (1) 50 patients with schizophrenia, (2) 50 patients with unipolar major depressive disorder, and (3) 50 individuals with no psychiatric history. Using an internally developed semistructured interview, psychometrically validated clinical outcome measures, and a multimodal sensing system utilizing video, acoustic, actigraphic, heart rate, and electroencephalographic sensors, we aim to evaluate the system's capacity in classifying subjects (schizophrenia, depression, or control), to evaluate the system's sensitivity to within-group symptom severity, and to determine if such a system can further classify variations in disorder subtypes., Results: Data collection began in July 2020 and is expected to continue through December 2022., Conclusions: If successful, this study will help advance current progress in developing state-of-the-art technology to aid clinical psychiatric assessment and treatment. If our findings suggest that these technologies are capable of resolving diagnoses and symptoms to the level of current psychometric testing and clinician judgment, we would be among the first to develop a system that can eventually be used by clinicians to more objectively diagnose and assess schizophrenia and depression with the possibility of less risk of bias. Such a tool has the potential to improve accessibility to care; to aid clinicians in objectively evaluating diagnoses, severity of symptoms, and treatment efficacy through time; and to reduce treatment-related morbidity., International Registered Report Identifier (irrid): DERR1-10.2196/36417., (©Robert O Cotes, Mina Boazak, Emily Griner, Zifan Jiang, Bona Kim, Whitney Bremer, Salman Seyedi, Ali Bahrami Rad, Gari D Clifford. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.07.2022.)

Background: Schizophrenia is a severe psychiatric disorder that causes significant social and functional impairment. Currently, the diagnosis of schizophrenia is based on information gleaned from the patient's self-report, what the clinician observes directly, and what the clinician gathers from collateral informants, but these elements are prone to subjectivity. Utilizing computer vision to measure facial expressions is a promising approach to adding more objectivity in the evaluation and diagnosis of schizophrenia., Method: We conducted a systematic review using PubMed and Google Scholar. Relevant publications published before (including) December 2021 were identified and evaluated for inclusion. The objective was to conduct a systematic review of computer vision for facial behavior analysis in schizophrenia studies, the clinical findings, and the corresponding data processing and machine learning methods., Results: Seventeen studies published between 2007 to 2021 were included, with an increasing trend in the number of publications over time. Only 14 articles used interviews to collect data, of which different combinations of passive to evoked, unstructured to structured interviews were used. Various types of hardware were adopted and different types of visual data were collected. Commercial, open-access, and in-house developed models were used to recognize facial behaviors, where frame-level and subject-level features were extracted. Statistical tests and evaluation metrics varied across studies. The number of subjects ranged from 2-120, with an average of 38. Overall, facial behaviors appear to have a role in estimating diagnosis of schizophrenia and psychotic symptoms. When studies were evaluated with a quality assessment checklist, most had a low reporting quality., Conclusion: Despite the rapid development of computer vision techniques, there are relatively few studies that have applied this technology to schizophrenia research. There was considerable variation in the clinical paradigm and analytic techniques used. Further research is needed to identify and develop standardized practices, which will help to promote further advances in the field., Competing Interests: NO authors have competing interests.

Considerable variation in clozapine utilization exists across the United States, and little is known about the perspective of psychiatrists in states with low clozapine use. To better understand clozapine practices, attitudes, and barriers, a survey was administered to a group of southeastern state conference attendees (SSCA; N = 86). The same survey was administered to psychiatrists belonging to a national community psychiatry organization (AACP; N = 57), and differences were analyzed across the two samples. In comparison to the AACP, the SSCA group felt less comfortable, perceived clozapine as less safe and effective, had fewer patients on clozapine, and were more likely to prefer antipsychotic polypharmacy to clozapine use. Across the sample, use of a myocarditis screening protocol was rare (N = 14/76; 18%) and less than half used plasma antipsychotic levels to guide dosage (N = 60/129; 47%). Continuing professional education on clozapine are needed for psychiatrists who see individuals with psychotic disorders., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Clozapine-induced myocarditis may be a hypersensitivity reaction due to titration that was too rapid for a patient's clozapine metabolism. Obesity, infections, and inhibitors (e.g., valproate) may lead to clozapine poor metabolizer (PM) status. The hypothesis that 4 patients with clozapine-induced myocarditis from two United States hospitals were clozapine PMs was tested by studying their minimum therapeutic clozapine doses and titrations. Methods: Using methodology from a prior myocarditis case series of 9 Turkish patients, we studied: 1) the concentration-to-dose (C/D) ratio; 2) minimum therapeutic dose required to reach 350 ng/ml (a marker for PM status); and 3) titration speed. Results: All 4 patients were possible clozapine PMs (their respective minimum therapeutic doses were: 134, 84, 119 and 107 mg/day). The identified possible contributors to clozapine PM status were: 1) valproate in Cases 1, 2 and 4; 2) obesity and a urinary tract infection in Case 2; and 3) obesity and very rapid titration in Case 4. Case 3, who was given a normal US titration, appeared to be a genetic clozapine PM. He developed clozapineinduced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome after rechallenge using 12.5 mg/day > 3 months later. The results were similar to 9 Turkish cases, all of which were PMs (6 on valproate, 4 with obesity, 1 with infection and 1 possibly genetic). Conclusions: Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced myocarditis could be explained by lack of individualized titration. (Neuropsychopharmacol Hung 2022; 24(1): 29-41).

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration., Competing Interests: In the last 3 years, the following authors had no conflict of interest: Drs. de Leon, Schoretsanitis, Molden, Smith, Solismaa, Švancer, Olmos, Ricciardi, Iglesias-Garcia, Iglesias-Alonso, Spina, Ruan, Chuan-Yue Wang, Gang Wang, Tang, Lin, Lane, Rajkumar, González-Esquivel, Jung-Cook, Baptista, Rohde, Nielsen, Verdoux, Quiles, Sanz, De las Cuevas, Cohen, Schulte, Chopra, McCollum, Shelton, Kaithi, Farooq, McGrane, Lana, Arrojo-Romero, Rădulescu, Every-Palmer, Bebawi, Bhattacharya, Otsuka, Lazary, Torres, Yecora, Motuca, Chan, Zolezzi, Ouanes, De Berardis, Grover, Kirilochev, Soloviev, Ayub, Silva, Bonelli, Temmingh, Decloedt, Pedro, Pacheco Palha, LLerena, Fernandez-Egea, Siskind, Masmoudi, Mohd Saffian, Leung and Buckley. In the last 3 years several authors report conflicts of interests. Dr. Seppälä is permanent medical advisor, received lecture fees and is an advisory board member from Viatris that markets clozapine in Finland and other European countries. Dr. Kopeček participated in speakers/advisory boards and lectured with the support of Angelini, Janssen Pharmaceuticals, Lundbeck and Richter Gedeon. Dr. Yong Sik Kim received grants, research support and honoraria from Janssen, Otsuka, Whan in Pharm and Bukwang Pharm (Sumitomo Dannipon Pharma). Dr. Se Hyun Kim received research grants from and/or served as a lecturer for Janssen, Eli Lilly, and Dongwha. Dr. Ertuğrul has received speaker’s honoraria from Abdi İbrahim Otsuka. Dr. Anıl Yağcıoğlu has received speaker’s honoraria and consulting fees from Janssen and Abdi İbrahim Otsuka. Dr. Cotes has received research funding from Otsuka, Lundbeck, Roche, Alkermes, and is a consultant for Saladax Biomedical. Dr. Kane reports personal fees from Alkermes, personal fees from Allergan, personal fees from Bristol-Myers Squibb, personal fees from IntraCellular Therapies, Janssen, Lundbeck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Reviva, Sunovion, Takeda, Teva, outside-the-submitted work from LB Pharma, MedAvante and The Vanguard Research Group. Dr. Ng had served as consultant for Grunbiotics, Lundbeck, Servier, and Janssen-Cilag, and received research speaker honoraria from Servier, Janssen-Cilag and Pfizer.IMcG received royalties from Hogrefe Publishing Corp. T.L. Dr. Bilbily is supported by the National Institute on Drug Abuse training grant 5T32DA007261-30 (MPI). Dr. Hiemke received speaker’s honoraria from Otsuka. Dr. López-Jaramillo reports financial support for research from Financial support from the National Institute of Mental Health, USA, MinCiencias, Colombia and the Universidad de Antioquia, Colombia. Dr. Eap received honoraria for conferences or teaching CME courses from Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Vifor-Pharma, and Zeller. Dr. Seifritz has received honoraria from Schwabe GmbH for educational lectures. He has further received educational grants and consulting fees from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Recordati, Vifor, Sunovion, and Mepha. Dr. Bousman is a member of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Pharmacogene Variation Consortium (PharmVar). Dr. Kelly has served as a consultant for Alkermes, Lyndra and Sunovion. Dr. Procyshyn has been on the speaker's bureau and attended advisory board meetings for Janssen, Lundbeck, and Otsuka. Dr. Adebayo was on the advisory board of Janssen for a Long Acting Injectable Paliperidone palmitate in Nigeria. Janssen is not involved in Clozapine in Nigeria. Dr. Fountoulakis has received grants in the past, served as consultant, advisor or CME speaker, or received support to attend congresses by the following entities: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Pfizer, the Pfizer Foundation, Sanofi-Aventis, Servier, Shire and others. Since January 2020 he has been the director of Cochrane Greece and completely free from any conflict of interest. Dr. Wilkowska has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen-Cilag, Lundbeck, Polpharma, Sanofi and Valeant. Dr. Cubała has received research support from Alkermes, Allergan, Auspex, Biogen, Celon, Ferrier, Forest Laboratories, Janssen, Otsuka, and Sanofi; he has served on speaker bureaus for Angelini, Celon, Janssen, and Sanofi, and he has served as a consultant for GW Pharmaceuticals, Janssen, Celon and Sanofi. Dr. Villagrán-Moreno has received speakerʼs honoraria from Janssen and have developed lectures and presented clozapine lectures for Adamed, which sells clozapine in Spain; he has participated in advisory boards for Rovi and in research projects for Otsuka. Dr. Crespo-Facorro has received funding unrelated to the present work for research projects and/or honoraria as a consultant or speaker from the following entities: Angelini, Janssen-Cilag, Lundbeck, Otsuka, Mylan, Sanofi-Aventis, ADAMED, Agencia Española de Investigacion, Instituto de Salud Carlos III, the EU Seventh Framework Program and Horizon 2020. Dr. Takeuchi has received speaker’s fees from EA Pharma, Kyowa, Janssen, Lundbeck, Meiji Seika Pharma, Mochida, Otsuka, Sumitomo Dainippon Pharma, Takeda, and Yoshitomiyakuhin. Dr. Tsukahara has received speaker's honoraria from Eisai Inc. Dr. Gründer has served as a consultant for Allergan (Dublin, Ireland), Boehringer Ingelheim (Ingelheim, Germany), Institute for Quality and Efficiency in Health Care (IQWiG, Cologne, Germany), Janssen-Cilag (Neuss, Germany), Lundbeck (Copenhagen, Denmark), Otsuka (Chiyoda, Japan), Recordati (Milan, Italy), Sage (Cambridge, USA), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Gedeon Richter (Budapest, Hungary), Janssen Cilag, Lundbeck, Otsuka, Recordati. He has received grant support from Boehringer Ingelheim, Lundbeck and Saladax (Bethlehem, USA). He is co-founder and/or shareholder of Mind and Brain Institute GmbH (Zornheim, Germany), Brainfoods GmbH (Zornheim, Germany), OVID Health Systems GmbH (Berlin, Germany) and MIND Foundation gGmbH (Berlin, Germany). Dr. Sagud participated in lectures for the following companies: Alkaloid, Belupo, Elli Lilly, Gedeon Richter, Jadran Galenski Laboratorij, Johnson / Johnson, Lundbeck, Makpharm, Pliva, Stada and participated in the clinical trial: Eli Lilly, Krka and Gedeon Richter. Dr. Celofiga received speaker’s honoraria from Ely Lilly, Lundbeck, Richter Gedeon, Krka, Lek, Pliva, Angelini Pharma and participated in advisory boards for Janssen Pharmaceuticals and Lundbeck. Dr. Ignjatovic Ristic developed and presented clozapine lectures with the support of Mylan, received speakerʼs honoraria from Mylan, Teva Serbia, Pharm Swiss, Krka and Janssen. Dr. Ortiz has been a consultant and has received honoraria from Janssen-Cilag. Dr. Elkis received research grants from the São Paulo Research Support Foundation (FAPESP) and honoraria for participation as a member of advisory boards, speaker, or travel support from the following pharmaceutical companies: Aché, Cristalia, Daiichi-Sankyo, Janssen, Mantecorp-Hypera, Sandoz, and Teva. Dr. Weizman received speakerʼs honoraria from Lundbeck, Lilly, Teva, Trima, Jansen, Medison, Novartis and AstraZeneca. These activities were unrelated to the current study. Dr Marder reports consultation fees from Roche, Sunovion, Merck, Boehringer Ingelheim and Otsuka. He reports research support from Boehringer-Ingelheim, and GW Pharma. Dr. Citrome has engaged in collaborative research with, or received consulting or speaking fees, from: AbbVie, Acadia, Alexza, Alkermes, Allergan, Angelini, Astellas, AstraZeneca, Avanir, Axsome, BioXcel, Boehringer Ingelheim, Bristol-Myers Squibb, Cadent Therapeutics, Eisai, Eli Lilly, Forum, Genentech, Impel, Indivior, Intra-Cellular Therapies, Janssen, Jazz, Karuna, Lundbeck, Luye, Lyndra, Medavante-Prophase, Meiji, Merck, Medivation, Mylan, Neurocrine, NeuroRx, Novartis, Noven, Osmotica, Otsuka, Pfizer, Reckitt Benckiser, Relmada, Reviva, Sage, Shire, Sunovion, Takeda, Teva, University of Arizona, Valeant, Vanda, and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research. Dr. Freudenreich has the following financial relationship with a commercial interest to disclose (recipient SELF; content area SCHIZOPHRENIA): Alkermes – Research grant (to institution), consultant honoraria (Advisory Board); Avanir – Research grant (to institution); Janssen – Research grant (to institution), consultant honoraria (Advisory Board); Integral - Consultant honoraria; Neurocrine – Consultant honoraria (Advisory Board); Novartis – Consultant honoraria; Otsuka – Research grant (to institution); Roche – Consultant honoraria; Springer Verlag – Royalties (medical writer); Elsevier – Honoraria (medical editing); Global Medical Education – Honoraria (CME speaker and content developer); Medscape – Honoraria (CME speaker); American Psychiatric Association – Consultant honoraria (SMI Adviser); Wolters-Kluwer – Royalties (content developer); UpToDate – Royalties, honoraria (content developer and editor, including for a chapter on clozapine). Dr. Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Damitsa, Gedeon Richter, Hikma, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of LB Pharma. Dr. Müller reports he has been a co-investigator for two pharmacogenetic studies where genetic test kits were provided as an in-kind contribution by Myriad Neuroscience. He did not receive any payments or any equity, stocks, or options from any pharmacogenetic companies. He is also a co-inventor of two patents assessing risk for antipsychotic-induced weight gain (pending)., (Thieme. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Clozapine clinics can facilitate greater access to clozapine, but there is a paucity of data on their structure in the US., Methods: A 23-item survey was administered to participants recruited from the SMI Adviser Clozapine Center of Excellence listserv to understand characteristics of clozapine clinics., Results: Clozapine clinics (N = 32) had a median caseload of 45 (IQR = 21-88) patients and utilized a median of 5 (IQR = 4-6) interdisciplinary roles. The most common roles included psychiatrists (100%), pharmacists (65.6%), nurses (65.6%), psychiatric nurse practitioners (53.1%), and case managers (53.1%). The majority of clinics outreached to patients who were overdue for labs (78.1%) and had access to on-site phlebotomy (62.5%). Less than half had on call services (46.9%)., Conclusions: In this first systematic description of clozapine clinics in the US, there was variation in the size, staffing, and services offered. These findings may serve as a window into configurations of clozapine teams., (© 2021. The Author(s).)

The COVID-19 pandemic has catalyzed structural changes in the public mental health sector, including a shift to telehealth and telesupervision, financial strain for community mental health organizations and clinicians, and risk of burnout among clinicians and staff. This Open Forum considers how technical assistance organizations have supported community mental health providers in adapting to these changes. Moving forward, knowledge gained through this work can help to build the body of practice-based evidence to inform future technical assistance activities in a postpandemic world.

Despite its unique efficacy, clozapine remains underutilized in the United States. Perceptions about clozapine and barriers to its use have been examined among prescribers, but insufficiently studied among consumers. We surveyed 211 antipsychotic consumers (86 on clozapine and 125 on other antipsychotics) on their medication-related perspectives in a public hospital system in Atlanta, Georgia, USA. In contrast to their previous regimen, 72% of clozapine consumers reported they were more satisfied with clozapine. When compared with consumers taking other antipsychotics, clozapine consumers reported more side effects but did not differ on other measures of satisfaction or efficacy. We found Caucasians to be overrepresented among clozapine, as compared to other antipsychotic consumers. Side effects most strongly associated with poor safety ratings were sedation, limb jerking, and dizziness when standing. However, clozapine was only rated less safe by consumers who experienced more than one of these side effects. We used an unsupervised clustering approach to identify three major groups of clozapine consumers. Cluster A (19%) had the lowest safety ratings, aversion to blood work, and a high rate of side effects that associate with lower safety ratings. Cluster B (25%) experienced more hospitalizations and reported satisfaction with clozapine that correlated with efficacy ratings, irrespective of safety ratings. Cluster C (56%) experienced fewer hospitalizations, fewer previous drug trials, greater educational attainment, lower rates of smoking, and rated clozapine more highly. This work identifies common side effects that influence the subjective safety of clozapine and suggests that attitudes toward clozapine depend on context-specific factors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Introduction: To investigate the patterns and correlates of antipsychotic prescriptions among recently discharged inpatients with schizophrenia in China., Methods: The study included discharged patients from 41 tertiary psychiatric hospitals in 29 provinces between March 19-30, 2019. A total of 1032 inpatients with schizophrenia were included. Socio-demographic and clinical data were retrieved from medical records upon discharge., Results: Patients received a total of 13 unique antipsychotic medications, which included 9 s-generation antipsychotics (SGAs) and 4 first-generation antipsychotics (FGAs). The utilization rates of SGAs and FGAs were 98.8 % and 6.1 % respectively. The three most commonly antipsychotic medications were risperidone (35.1 %), olanzapine (31.3 %), and clozapine (24.6 %). The mean chlorpromazine equivalent dose was 452.12 ± 230.74 mg/day. The utilization rate of mood stabilizers was 18.9 %, 8.8 % for antidepressants, 20.3 % for sleep improvers, and 9.9 % for anticholinergics. More than two fifths patients (43.1 %) received two or more antipsychotic medications. Predictors of antipsychotic polypharmacy included younger age, residing in Central or West China, a longer duration of illness, a history of prior hospitalizations, and having agitated behavior during the hospitalization., Conclusion: Antipsychotic polypharmacy in China is common on inpatients settings. The proportion of antipsychotic polypharmacy in China is higher than in many other countries, despite limited data to support the efficacy of many combinations. Clozapine remains one of most commonly prescribed antipsychotics in China, either as a monotherapy or combination therapy., (Copyright © 2021. Published by Elsevier B.V.)

Background: The off-label use of antipsychotic medications is common in many countries, and the extent of such use in psychiatric inpatients in China has not been sufficiently studied. The purpose of this study was to survey the incidence and examine the correlates of off-label antipsychotic use in a large, nationally-representative sample in China., Methods: This study included discharged psychiatric patients between March 19 and 31, 2019 from 41 tertiary psychiatric hospitals across 29 provinces in China. Their socio-demographic and clinical data were collected and analyzed., Results: After excluding patients with schizophrenia spectrum disorder or bipolar disorder, 981 patients were included in the analysis. Overall, antipsychotics were prescribed to 63.2% (95%CI 60.2-66.2%) of the sample. Antipsychotics were used in a wide spectrum of psychiatric disorders, with the rate being the highest among patients with dissociative (conversion) disorders (89.9, 95%CI 83.0-94.8%), organic mental disorders (81.7, 95%CI 73.1-88.7%), dementia (79.0,95%CI 67.8-87.9%), obsessive-compulsive disorder (77.8, 95%CI 55.7-92.5%), mental disorders due to psychoactive substances (75.3,95%CI 64.7-84.2%), behavioural and emotional disorders with onset usually occurring in childhood and adolescence (71.4, 95%CI 45.5-90.1%), somatoform disorders (63.2, 95%CI 40.8%-82..2%), major depression disorder (53.7,95%CI 48.8-58.6%), anxiety disorder (38.8,95%CI 30.5-47.7%), and insomnia (25.0, 95%CI 8.5-28.9%). The top three most commonly used antipsychotics were olanzapine (29.1%), quetiapine (20.3%) and risperidone (6.8%), and their corresponding average doses were 9.04 ± 5.80 mg/day, 185.13 ± 174.72 mg/day, and 2.98 ± 1.71 mg/day, respectively. A binary logistic regression showed that younger age, having the Employee Health Insurance or Residents Health Insurance, having psychotic symptoms and requiring restraint during hospitalization were significantly associated with off-label use of antipsychotics., Conclusion: Off-label use of antipsychotics is very common in psychiatric inpatients in China, mainly with moderate-dose use of single agents. However, the efficacy and safety of this practice is uncertain for many diagnoses and for the elderly. Clinicians should be cautious about this practice while waiting for more research data., (© 2021. The Author(s).)

Objectives: The number of International Medical Graduate (IMG) physicians matching into categorical psychiatry decreased steadily over the past decade. The authors sought to understand if this trend was occurring in other specialties, if US IMG physicians and non-US IMG physicians were equally affected, and if certain regions of the USA were more affected by this decrease than others. Finally, the authors compared the proportion of foreign-born individuals within a US census region to the proportion of non-US IMG physicians within that region., Methods: The authors analyzed data from the National Resident Matching Program from the years 2014-2020. Statewide data was aggregated into nine geographic regions, as per the US Census Bureau. The number of foreign-born individuals within each US census region was calculated from the 2018 American Community Survey data., Results: In comparison to eight other specialties, psychiatry saw the greatest decrease (46.3%) in IMG physicians matching into PGY-1 positions. Both US IMG physicians and non-US IMG physicians were equally affected. The percentage of IMG physicians decreased in each of the nine US census regions. In six out of nine geographic regions, non-US IMG physicians were under-represented when comparing their proportion to the number of foreign-born people that lived within that region., Conclusions: Decreasing numbers of IMG physicians in psychiatry training may have long-term implications for cultural competency, serving underserved populations, and fellowship recruitment. We advocate for program directors to recognize IMG physicians as an important source of diversity and to recruit residents that reflect the communities they serve.

Background and Objectives: As many as 30% of individuals with a schizophrenia spectrum disorder experience obsessive-compulsive symptoms (OCS). Clozapine has demonstrated superior efficacy for the treatment of medication-resistant schizophrenia but it is also associated with an increased risk for OCS. Because pharmacologic management of clozapine-related OCS can be particularly challenging, cognitive behavioral therapy (CBT) should be considered. Nevertheless, there are few detailed accounts of CBT for OCS and schizophrenia., Methods: The authors describe the interdisciplinary outpatient care of a client who had a 25-year history of schizoaffective disorder, bipolar type, and OCS. The case formulation was used to guide interventions to target core schemas of being dangerous and defective. The case study describes the cognitive behavioral formulation, treatment targets, treatment course, and functional and symptom response., Results: The client received 21 sessions of a formulation-based CBT for psychosis protocol, which included a 6-session course of exposure with response prevention, consisting of imaginal and in vivo exposure to multiple salient harm stimuli. Reduced ratings of distress and a 50% reduction in OCS suggest that habituation and inhibitory learning occurred. The treatment of OCS resulted in the complete resolution of thought broadcasting. Subsequently, the client was more successful in his efforts to adhere to an action schedule., Limitations: The use of both the treatment approach described in this clinical case report and contemporaneous medication management preclude comment on the mechanism(s) of the therapeutic change observed in this case., Conclusions: This report presents a means of conceptualizing the interplay between thought broadcasting and harm obsessions and discusses considerations in identifying and treating individuals with similar comorbid conditions, particularly in the context of clozapine treatment for medication-resistant psychosis.

Objective: Second-generation antipsychotics vary in their propensity to cause serious cardiometabolic side effects. In addition, use of two or more antipsychotics (polypharmacy) may lead to additive side effects and has not been shown to be consistently more effective than monotherapy. This study examined the use of academic detailing with audit and feedback to improve antipsychotic prescribing practices, including antipsychotic polypharmacy and utilization of medication with high or low risk of cardiometabolic side effects ("high risk" or "low risk," respectively)., Methods: Four intervention sessions were provided over two years to psychiatric care providers at community mental health centers. Segmented regression within the general estimating equation model framework used Medicaid pharmacy claims to examine prescribing patterns before and after the intervention among all beneficiaries (67,721 person-months) over a five-year period., Results: After the intervention, 10.9% of beneficiaries with antipsychotic claims were on polypharmacy, compared with 13.1% before the invention. Use of high-risk and low-risk antipsychotics did not change. The final adjusted polypharmacy model showed that antipsychotic polypharmacy decreased among young adults and adults ages 40 or older compared with beneficiaries ages 30-39 (β=-.02, p=.04, and β=-.02, p=.007, respectively). The raw proportion of beneficiaries on high- and low-risk agents did not change, although final adjusted models demonstrated changes in use of high- and low-risk agents by diagnosis and risk group., Conclusions: Polypharmacy decreased among young and older adults after academic detailing with audit and feedback. Although further research is needed, this low-intensity intervention may help mental health systems reduce antipsychotic polypharmacy.

Antipsychotic polypharmacy (APP) is a common strategy despite guidelines advising against this practice. This article seeks to quantify the prevalence and correlates of APP using Medicaid Analytic eXtract files from 2003 to 2004. Nineteen percent of Medicaid recipients who received an antipsychotic were treated with APP. Individuals who received APP were more likely to be white, male, disabled, between the ages of 18-29, diagnosed with a psychotic disorder, and diagnosed with a higher number of psychiatric conditions. Geographic variation in APP rates was also observed. Quality improvement initiatives may help reduce APP for medically vulnerable patients.

: Synthetic cathinones are a class of novel psychoactive substances. α-Pyrrolidinopentiophenone (α-PVP), or "Flakka", is one of these substances. Users often present acutely psychotic or agitated. We present the case of a 20-year-old male without prior psychiatric history who was brought to the hospital by his family because of increasingly bizarre and erratic behavior after reported ingestion of Flakka. What ensued was a prolonged course of psychosis and severe catatonia. Synthetic cathinones are thought to cause catatonia in approximately 1% of cases. Awareness of the possible presentations associated with α-PVP intoxication is increasingly important and should be further explored, as they can have important implications in setting expectations for care. Additionally, providers should have a low threshold for asking patients about bath salt ingestion.

Clozapine-induced neutropenia occurs in 3-5% of individuals treated with clozapine. Current US guidelines require interruption of clozapine when the absolute neutrophil count (ANC) drops below 1000 cells/mm 3 . There is minimal available guidance for what dosing schedule to use when restarting clozapine after an episode of neutropenia. Here, we present a case of a 50-year-old Caucasian female with a history of schizoaffective disorder who was successfully rechallenged on clozapine one month after developing clozapine-induced neutropenia (ANC 600 cells/mm 3 ). To understand published re-titration rates of clozapine after neutropenia, we conducted a literature review using a using the PubMed database and found only seven case reports that unambiguously reported a clozapine dosing schedule during re-challenge. All were successful except one, a case of clozapine rechallenge after agranulocytosis. Including this case presentation, six out of eight cases restarted clozapine more cautiously than recommended by the US guidelines for a new clozapine initiation. We cannot comment what role a slower or more rapid titration plays in a successful rechallenge after neutropenia with the available evidence. We encourage researchers to publish their dosing schedule in detail after an episode of neutropenia or agranulocytosis.

Given the heterogeneity of symptoms in patients with schizophrenia and current treatment limitations, biomarkers may play an important role in diagnosis, subtype stratification, and the assessment of treatment response. Though many potential biomarkers have been studied, we have chosen to focus on some of the most promising and potentially clinically relevant biomarkers to review herein. These include markers of inflammation, neuroimaging biomarkers, brain-derived neurotrophic factor, genetic/epigenetic markers, and speech analysis. This will provide a broad overview of putative biomarkers that could become clinically relevant in the future, though none currently appear ready to assist the clinician in identifying cases of schizophrenia, subtypes of the disorder, treatment choice, or response. Nonetheless, some biomarkers, such as C-reactive protein (CRP), may be useful at identifying individuals who may be more highly inflamed, which could drive treatment choice. Though checking CRP is not a standard of practice, this is one example of how biomarkers may drive treatment decisions in the future, supporting precision medicine. Similarly, technological advances may one day allow clinicians to detect changes in speech patterns, which could represent a noninvasive, clinically useful tool in the future. We conclude the review by highlighting two important potential clinical uses for biomarkers in schizophrenia: the identification of individuals who may convert from clinical high risk and the stratification of patients via different biomarkers that may supersede clinical diagnosis. Given the enormous burden of illness of schizophrenia, the search for clinically relevant biomarkers is of great importance to improve the lives of patients with the disorder., (Copyright © 2018 by the American Psychiatric Association.)

Not only must the 21st-century psychiatrist adapt to a rapidly advancing science and changing health care climate, he or she must also consider how to most effectively educate the psychiatrists of tomorrow. Psychiatric education is changing and is influenced by the experiences, attitudes, beliefs, and preferences of today's learner. The Millennial Generation, the cohort of individuals born between 1981 and 2000, now represents the majority of the trainees entering medical school and psychiatry residency. This column provides an overview of generational differences in medicine and gives the reader a set of concrete strategies for working with Millennial learners in psychiatry most effectively. In general, Millennials enjoy collaborative learning, perform well in groups, are technologically savvy, appreciate clear expectations, and expect frequent and individualized feedback about their performance. Educators must determine what works best for each individual, create a culture of inquiry, and, most important, fuel a spirit of lifelong learning., (Copyright © 2018 by the American Psychiatric Association.)

Objectives: This study evaluated changes in cardiometabolic monitoring for children and adolescents who were prescribed an antipsychotic medication in a state mental health system before and after a quality improvement intervention., Methods: The intervention included education for prescribers, auditing on metabolic monitoring, and feedback to mental health center leaders regarding their monitoring. Research staff extracted yearly data on cardiometabolic monitoring from randomly selected community mental health center records before and after the intervention. Pre- and postintervention changes in monitoring were assessed with chi-squared tests., Results: Evidence of past year monitoring increased: for glucose 18.9%-42.1% (χ 2  = 6.75, p < 0.001), for triglycerides 13.5%-31.0% (χ 2  = 4.54, p = 0.033), for cholesterol 13.5%-33.1% (χ 2  = 5.48, p = 0.019), and for weight 67.6%-84.1% (χ 2  = 5.21, p = 0.022). Rates of monitoring for blood pressure and waist circumference increased but not significantly. In both years studied, weight was obtained most frequently and waist circumference was obtained least frequently., Conclusions: Monitoring rates significantly improved for four out of six parameters evaluated, but overall monitoring rates remained low at the end of the study period. Prescriber education with audit and feedback may improve cardiometabolic monitoring rates, but research is needed to evaluate barriers to monitoring in children.

Antipsychotic medications can cause serious cardiometabolic side effects. No recent research has broadly evaluated monitoring and strategies to improve monitoring in U.S. public mental health systems. To address this knowledge gap, we evaluated education with audit and feedback to leaders to improve cardiometabolic monitoring in a state mental health system. We used Chi square statistics and logistic regressions to explore changes in monitoring recorded in randomly sampled records over 2 years. In 2009, assessment of patients on antipsychotics was 29.6 % for cholesterol, 40.4 % for glucose, 29.1 % for triglycerides, 54.3 % for weight, 33.6 % for blood pressure, and 5.7 % for abdominal girth. In 2010, four of ten mental health centers improved their rate of adult laboratory monitoring. Overall monitoring in the state did not increase. Education for prescribers with audit and feedback to leaders can improve monitoring in some settings, but more intensive and/or prolonged interventions may be required.

Cocaine, the third mostly commonly used illicit drug in the United States, has a wide range of neuropsychiatric effects, including transient psychotic symptoms. When psychotic symptoms occur within a month of cocaine intoxication or withdrawal, the diagnosis is cocaine-induced psychotic disorder (CIPD). Current evidence suggests those with CIPD are likely to be male, have longer severity and duration of cocaine use, use intravenous cocaine, and have a lower body mass index. Differentiating CIPD from a primary psychotic disorder requires a detailed history of psychotic symptoms in relation to substance use and often a longitudinal assessment. Treatment includes providing a safe environment, managing agitation and psychosis, and addressing the underlying substance use disorder. This review begins with a clinical case and summarizes the literature on CIPD, including clinical presentation, differential diagnosis, mechanism and predictors of illness, and treatment.

Objective: Electroconvulsive therapy (ECT) was first introduced in China in the early 1950s and has evolved into a significant psychiatric treatment. Research from Chinese psychiatrists provides important clinical data for ECT practitioners. However, most of the research has only been published in Chinese language journals. This article summarizes data from publications in the Chinese scientific community related to the clinical practice of ECT and research on efficacy in the treatment of psychiatric disorders., Methods: Descriptive study primarily based on Chinese language literature identified from searches of the China National Knowledge Infrastructure and the Medline databases (1979-2012)., Results: More than 900 journal papers on ECT have been published in the Chinese language between 1979 and 2012. Currently, modified ECT has replaced unmodified ECT, and treatments were performed both in inpatient and outpatient settings. Electroconvulsive therapy is primarily used for the treatment of schizophrenia and mood disorders and has been shown to be very effective in both. The primary use of ECT in China is in the treatment of schizophrenia. The Chinese literature provides a rich database on the efficacy of modified and unmodified ECT, with and without adjunctive antipsychotics, in the treatment of schizophrenia., Conclusion: The Chinese medical literature provides an important database that will help advance the practice of ECT in both China and the international community.