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Negative symptoms can be an integral part of schizophrenia spectrum pathology and can be secondary to other psychotic symptoms or caused by antipsychotic medication. As antipsychotic drugs differ in their affinity to dopamine receptors and some antipsychotics have partial agonistic effects, antipsychotic drugs are expected to vary in their ability to cause negative symptoms. The association between negative symptoms and antipsychotic medication divided into partial agonists, or antagonists with high or low D 2 affinity was assessed in 310 remitted first episode psychosis (FEP) patients. Severity of negative symptoms was assessed with the Comprehensive Assessment of Symptoms and History, and the Positive and Negative Syndrome Scale. Linear regression analyses were performed while controlling for differences in clinical and sociodemographic characteristics between the groups using inverse probability of treatment weighting. Patients using partial agonists (n = 78) showed fewer negative symptoms compared to those using high affinity antagonists (n = 84). Patients using partial agonists displayed less severe negative symptoms compared to those using low affinity antagonists (n = 148) at a trend level (p = 0.051). Negative symptom severity was higher in patients who had higher antipsychotic doses. In remitted FEP patients, we observed that the use of antipsychotic medication classified as partial agonists was associated with lower severity of negative symptoms, while the use of antagonists with high D 2 affinity was associated with more severe negative symptoms. • In remitted FEP patients, persistence of negative symptoms reduces quality of life and social and vocational recovery. • FEP patients using antipsychotics with partial D2R agonism showed less severe negative symptoms than high affinity antagonists. • There was a trend that FEP patients on partial agonists had milder negative symptoms than those on low affinity antagonists • Aripiprazole treatment was related to less severe negative symptoms, a potentially important advantage for recovery. [ABSTRACT FROM AUTHOR]

Most individuals in recovery are likely to attempt discontinuing their prescribed medication at least once. The collection of articles in this special issue uses research with quantitative and qualitative methods, reviews of the literature, conceptualization of theory, and first-person accounts from various perspectives to begin to shift the field of psychiatric rehabilitation from a narrow focus on symptom reduction and a fear-driven emphasis on medication adherence to a new perspective in which dilemmas and strong feelings about medication use are commonplace. We issue a call to action for training psychiatric rehabilitation practitioners, who often have the most direct and frequent interactions with people in recovery, to explore their clients' experiences with using medication and its impact on a range of life domains. Rehabilitation, recovery, and medication have ongoing mutual influences and require an inclusive, multidimensional framework that integrates complex ongoing interactions between personal, societal, and biological processes and assures that treatment decisions are in alignment with recovery goals. Impact and Implications: Although most individuals in recovery attempt discontinuing prescribed medications, many psychiatric rehabilitation practitioners shy away from discussing the topic. Psychiatric rehabilitation practitioners, who often have the most frequent interactions with people in recovery and frequently observe firsthand the positive and negative consequences of medication, should explore medication-related issues with their clients as part of multidimensional framework that integrates ongoing interactions between personal, societal, and biological processes. [ABSTRACT FROM AUTHOR]

Abstract Background It has been found that patients with schizophrenia are often accompanied by concomitant changes in inflammation levels during acute exacerbations, and some studies have suggested that the inflammatory indices neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) may be biomarkers of acute exacerbations in schizophrenia; however, few studies have simultaneously explored the differences in these inflammatory indices in the drug-free patients with schizophrenia in acute phase (DSA), medicated patients with schizophrenia in acute phase (MSA), medicated patients with schizophrenia in remission period (MSR), as well as the effects of different antipsychotic medications on inflammatory indices. Method A total of 651 subjects including 184 healthy controls (HC), 167 DSA, 119 MSA, and 181 MSR were included in this study. Demographic and disease information was collected from each individual and venous blood was collected to detect immune cells and calculate the inflammatory indices NLR, PLR, and MLR, and statistical methods such as analysis of variance (ANOVA) and multiple comparisons were utilized to explore the alteration of these inflammatory indices under the influence of different antipsychotics and in HC, DSA, MSA, and MSR. Results NLR was significantly higher in DSA and MSA than in HC after adjusting the confounders of sex, age, smoking, years of education, marital status, BMI, diabetes, and hypertension. PLR and MLR were not significantly different in patients with schizophrenia and in HC, and were not significantly different in patients with schizophrenia in any group. In MSA and MSR, NLR was positively correlated with disease duration and negatively correlated with the use of mood stabilizers. Conclusions NLR was significantly increased in acute phase of schizophrenia, regardless of use of antipsychotic drugs, but not significantly increased in stable phase, which might be a promising biomarker for acute phase of schizophrenia.

Introduction Short-term exposure to antipsychotics has proven to be beneficial. However, naturalistic studies are lacking regarding the long-term use of antipsychotics. This study aimed to investigate changes in use of antipsychotics over 20 years after a first-episode schizophrenia. Methods This study is part of the Danish OPUS trial (1998–2000), including 496 participants with first-episode schizophrenia. Participants were reassessed four times over 20 years. The main outcomes were days on medication, redeemed prescriptions of clozapine, psychiatric hospitalizations, and employment. Results At the 20-year follow-up, an attrition of 71% was detected. In total, 143 out of 496 participated, with 36% (n = 51) in remission-of-psychotic-symptoms-off-medication. The lowest number of days on medication (mean [ s.d. ], 339 [538] days) was observed in this group over 20 years. Register data on redeemed antipsychotics were available for all trial participants (n = 416). Individuals in treatment with antipsychotics (n = 120) at the 20-year follow-up had spent significantly more days in treatment (5405 [1857] v. 1434 [1819] mean days, p = 0.00) and more had ever redeemed a prescription of clozapine (25% v. 7.8%, p = 0.00) than individuals who had discontinued antipsychotics (n = 296). Further, discontinuers had significantly higher employment at the 20-year follow-up (28.4% v. 12.5%, p = 0.00). Conclusion In a cohort of individuals with first-episode schizophrenia, 36% were in remission-of-psychotic-symptoms-off-medication. However, high attrition was detected, potentially affecting study results by inflating results from individuals with favorable outcomes. From register data, free from attrition, approximately 30% were in treatment with antipsychotics, and 70% had discontinued antipsychotics. Individuals in treatment had the least favorable outcomes, implying greater illness severity. [ABSTRACT FROM AUTHOR]

Introduction: Long-acting injectable (LAI) antipsychotic medications and clozapine are effective yet underutilized medical therapies in early intervention services. The purpose of this study was to conduct a pre-implementation evaluation of contextual determinants of early intervention programs to implement innovations optimizing LAI antipsychotic and clozapine use within a shared decision-making model. Methods: Semi-structured interviews explored barriers and facilitators to implementing LAI antipsychotics and clozapine in early intervention services. Participants were: prescribers (n = 2), non-prescribing clinicians (n = 5), administrators (n = 3), clients (n = 3), and caregivers (n = 3). Interviews were structured and analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0). Results: Participants were supportive of using LAI antipsychotics, despite barriers (e.g., transportation, insurance coverage), while most were unfamiliar with clozapine (Innovation). Critical incidents (e.g., COVID-19) did not interfere with implementation, while barriers included lack of performance measures; stigma affecting willingness to take medication; and clozapine considered to be a "last resort" (Outer Setting). Treatment culture was described as clientcentered and collaborative, and most participants indicated LAI antipsychotic use was compatible with clinic workflows, but some were in need of resources (e.g., individuals trained to administer LAI antipsychotics; Inner Setting). Participants on the healthcare team expressed confidence in their roles. Family education and collaborative decision-making were recommended to improve client/family engagement (Individuals). Participants related the importance of tracking medication compliance, addressing client concerns, and providing prescribers with updated guidelines on evidence-based treatment (Implementation Process). Discussion: Results may guide implementation strategy selection for future programs seeking to optimize the use of LAI antipsychotics and clozapine for early-phase schizophrenia, when appropriate. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic medications offer limited long-term benefit to about 30% of patients with schizophrenia. We aimed to explore the individual-specific imaging markers to predict 1-year treatment response of schizophrenia. Methods: Structural morphology and functional topological features related to treatment response were identified using an individualized parcellation analysis in conjunction with machine learning (ML). We performed dimensionality reductions using the Pearson correlation coefficient and three feature selection analyses and classifications using 10 ML classifiers. The results were assessed through a 5-fold cross-validation (training and validation cohorts, n = 51) and validated using the external test cohort (n = 17). Results: ML algorithms based on individual-specific brain network proved more effective than those based on group-level brain network in predicting outcomes. The most predictive features based on individual-specific parcellation involved the GMV of the default network and the degree of the control, limbic, and default networks. The AUCs for the training, validation, and test cohorts were 0.947, 0.939, and 0.883, respectively. Additionally, the prediction performance of the models constructed by the different feature selection methods and classifiers showed no significant differences. Conclusion: Our study highlighted the potential of individual-specific network parcellation in treatment resistant schizophrenia prediction and underscored the crucial role of feature attributes in predictive model accuracy. [ABSTRACT FROM AUTHOR]

Introduction: Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients’ own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials. Methods: Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208). The interview guide included open-ended questions on current and prior disease burden, symptoms, quality of life, and treatment experiences. Steps taken to reduce interview stress and secure the validity of data included interviewer sensitivity training specific to mental health conditions and schizophrenia, use of in-person interviews whenever possible and use of videoconferencing for remote interviews to promote trust and comfort, and working closely with clinical site staff to identify patient eligibility and willingness to participate. Transcripts based on audio recordings were content coded and analyzed using thematic analysis; a post-hoc quantitative content analysis was conducted. Results: Patients reported that the symptoms of schizophrenia negatively impacted their work, relationships, self-esteem, emotional health, and daily activities. Most patients had positive experiences with medications that alleviated hallucinations, depression, and anxiety. However, side effects of medications were associated with negative impacts on physical, emotional, behavioral, and cognitive health. Lack of energy/drowsiness, weight gain, mood changes, and involuntary movements were the most common side effects reported with the use of antipsychotic medications. Patients reported unmet treatment needs related to better symptom control and to improved social and physical functioning. Conclusion: Collection of qualitative information within a schizophrenia clinical development process provides value and insights into patients’ views on burden of illness, experiences with previous medications, and experiences following participation in a clinical trial and can inform design for future studies. [ABSTRACT FROM AUTHOR]

Introduction and purpose Cariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use. Methods and materials A review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist. Conclusions Cariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations. [ABSTRACT FROM AUTHOR]

Abstract Background Many factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients. Methods The QoL was assessed using the Schizophrenia Quality of Life Scale (SQLS). Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) and seven factors were extracted. Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety. Cognitive impairment was assessed using the Ascertain Dementia 8 (AD8). The Treatment Emergent Symptom Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used to evaluate the side effects of medications. Results We recruited 270 patients (male:142,52.6%, mean age:41.9 ± 9.4 years). Positive correlations were observed between SQLS and its subdomains with the total score of BPRS, PHQ-9, GAD-7, AD8, TESS, and RSESE (all P

Background: Many factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients. Methods: The QoL was assessed using the Schizophrenia Quality of Life Scale (SQLS). Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) and seven factors were extracted. Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety. Cognitive impairment was assessed using the Ascertain Dementia 8 (AD8). The Treatment Emergent Symptom Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used to evaluate the side effects of medications. Results: We recruited 270 patients (male:142,52.6%, mean age:41.9 ± 9.4 years). Positive correlations were observed between SQLS and its subdomains with the total score of BPRS, PHQ-9, GAD-7, AD8, TESS, and RSESE (all P < 0.005). Patients who were taking activating second-generation antipsychotics (SGAs) had lower scores on total SQLS, Motivation/ Energy domain of SQLS (SQLS-ME) as well as Symptoms/ Side effects domain of SQLS (SQLS-SS) compared to those taking non-activating SGAs (all P < 0.005). Multiple regression analysis showed that depressive/ anxiety symptoms and cognitive impairment had significant negative effects on QoL (P ≤ 0.001), while activating SGAs had a positive effect (P < 0.005). Blunted affect and unemployment were inversely associated with the motivation/energy domain (P < 0.001). Conclusion: Our findings emphasize the important role of depression/anxiety symptoms and cognitive impairment in the QoL of patients with chronic schizophrenia. Activating SGAs and employment may improve the QoL of these individuals. Trial registration: This protocol was registered at chictr.org.cn (Identifier: ChiCTR2100043537). [ABSTRACT FROM AUTHOR]

AbstractPatients with schizophrenia have higher odds of premature mortality than people in the general population. Adherence to antipsychotic medication can prevent relapse and rehospitalisations and is considered a critical component of schizophrenia treatment. Yet, studies examining the factors associated with medication adherence in this patient population in Ghana are limited. This study examined the association between medication beliefs and adherence, and whether the effect of medication beliefs on adherence is contingent on doctor–patient communication. Patients with schizophrenia (N = 117) provided the data for the current analysis. Data were analyzed using hierarchical linear regression. Results showed a significant positive association between medication beliefs (i.e., necessity beliefs) and adherence. Doctor-patient communication was positively associated with adherence. Further, the association between necessity beliefs and medication adherence was found to be contingent on doctor-patient communication. Specifically, the effect of necessity beliefs on medication adherence weakened at high levels of doctor-patient communication. Other results showed that the mean antipsychotic medication adherence score was 16.70 ± 6.51. Moreover, about 89.3% of the patients were accepting their antipsychotic medication (i.e., having low concerns but high necessity beliefs). Findings suggest that necessity beliefs and doctor-patient communication exert similar effects on medication adherence. [ABSTRACT FROM AUTHOR]

Abstract Background 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient’s feeling of autonomy and psychiatric rehabilitation. Case presentation We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. Conclusions Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. Impact and implications Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.

Background: 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient's feeling of autonomy and psychiatric rehabilitation. Case presentation: We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. Conclusions: Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. Impact and implications: Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery. [ABSTRACT FROM AUTHOR]

Oral atypical antipsychotic (OAAP) medications are the most commonly prescribed treatment for the management of schizophrenia symptoms. This retrospective study, using Medicaid claims data (2016–2020), followed patients for 12 months after initiating OAAP therapy. Study outcomes included OAAP adherence, switching, augmentation, healthcare resource utilization (HRU), and expenditures. All-cause and schizophrenia-related HRU and expenditures were compared between adherent and nonadherent cohorts. Among 13,007 included patients (39.1 ± 12.8 years of age, 57.0% male, 36.1% Black, 31.8% White, 9.7% Hispanic), 25.7% were adherent to OAAPs (proportion of days covered [PDC] ≥ 0.8). During the 1-year follow-up period, Black individuals were in possession of an OAAP for an average of 166 days compared to 198 and 202 days for White and Hispanic patients, respectively. Approximately 16% of patients switched OAAP medications and 3.2% augmented therapy with an OAAP added to their index medication. Nearly 40% of patients were hospitalized during follow-up and 68.4% had emergency department (ED) visits. A greater proportion of nonadherent patients had all-cause inpatient (41.7% vs. 34.1%, p < 0.001) and ED visits (71.7% vs. 58.8%, p < 0.001) compared to adherent patients. Annual total healthcare expenditures were $21,020 per patient; $3481 higher for adherent versus nonadherent patients. Inpatient expenditures comprised 44.6% and 30.6% of total expenditures for nonadherent and adherent patients, respectively. Hospitalized patients' total expenditures were $23,261 higher compared to those without a hospitalization. Adherence to OAAP medication is suboptimal and associated with increased utilization of costly hospital and ED resources. Efforts to improve therapies and increase medication adherence could improve clinical and economic outcomes among individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

Characterised by fever, altered mental status, muscle rigidity and autonomic dysfunction, neuroleptic malignant syndrome is a life-threatening idiosyncratic reaction to antipsychotic medication; around one in 10 cases end in cardiac arrest. The primary cause of neuroleptic malignant syndrome is dopamine receptor blockade, and the standard causative agent is an antipsychotic drug. While first-generation (typical) neuroleptics such as haloperidol, fluphenazine, trifluoperazine and prochlorperazine pose the greatest risk, neuroleptic malignant syndrome has been reported with second-generation (atypical) neuroleptics such as risperidone, clozapine, olanzapine and ziprasidone. Paramedic awareness of neuroleptic malignant syndrome as a neuropsychiatric emergency is paramount to reducing serious morbidity and even death in patients presenting with symptoms and a history of antipsychotic use. Treatment is individualised and based on clinical presentation, with supportive medical therapy being a key intervention. [ABSTRACT FROM AUTHOR]

IntroductionQualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients’ own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials.MethodsSemi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208). The interview guide included open-ended questions on current and prior disease burden, symptoms, quality of life, and treatment experiences. Steps taken to reduce interview stress and secure the validity of data included interviewer sensitivity training specific to mental health conditions and schizophrenia, use of in-person interviews whenever possible and use of videoconferencing for remote interviews to promote trust and comfort, and working closely with clinical site staff to identify patient eligibility and willingness to participate. Transcripts based on audio recordings were content coded and analyzed using thematic analysis; a post-hoc quantitative content analysis was conducted.ResultsPatients reported that the symptoms of schizophrenia negatively impacted their work, relationships, self-esteem, emotional health, and daily activities. Most patients had positive experiences with medications that alleviated hallucinations, depression, and anxiety. However, side effects of medications were associated with negative impacts on physical, emotional, behavioral, and cognitive health. Lack of energy/drowsiness, weight gain, mood changes, and involuntary movements were the most common side effects reported with the use of antipsychotic medications. Patients reported unmet treatment needs related to better symptom control and to improved social and physical functioning.ConclusionCollection of qualitative information within a schizophrenia clinical development process provides value and insights into patients’ views on burden of illness, experiences with previous medications, and experiences following participation in a clinical trial and can inform design for future studies.

Schizophrenia is a chronic mental disorder characterized by severe cognitive and behavioral impairments. It often coexists with multiple and complex anxiety symptoms that exacerbate the clinical challenges associated with schizophrenia. This case report presents the history of a 32-year-old woman with a final diagnosis of both paranoid schizophrenia and mixed anxiety disorders. The patient presented with persistent auditory pseudohallucinations, severe anxiety together with occasional panic attacks, which were treated with a variety of antipsychotics. Treatment adjustments were necessitated by the emergence of side effects, including neutropenia, motor disturbances and the observation of major anxiety symptoms, including panic disorder. Ultimately, the successful use of quetiapine in monotherapy was achieved. This case study emphasizes the need for comprehensive treatment strategies to address the complex interplay of psychotic and anxiety symptoms. Increased clinical awareness and targeted treatment of comorbid anxiety can significantly improve the quality of life of patients with schizophrenia.

Kristin Richards,1 Michael Johnsrud,1 Christopher Zacker,2 Rahul Sasané2 1TxCORE, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA; 2Cerevel Therapeutics, LLC, Cambridge, MA, USACorrespondence: Kristin Richards, TxCORE, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Mail Stop A1930, Austin, TX, 78712, USA, Tel +1 512 471 5607, Email krichards@austin.utexas.eduPurpose: To examine 1-year persistence with oral atypical antipsychotics (OAAPs) for Medicaid patients with schizophrenia and assess the association between OAAP persistence and hospital and emergency department (ED) resource utilization.Patients and Methods: Using 2016– 2020 multi-state Medicaid claims data, this retrospective study followed patients diagnosed with schizophrenia for 12 months after initiating OAAP therapy. Patients started on an OAAP with no evidence of antipsychotic use in the previous 6 months were included if they had a diagnosis of schizophrenia, were not dually enrolled in Medicaid and Medicare, did not switch to a long-acting injectable antipsychotic, and were continuously eligible 6 months before and 12 months after the initial OAAP prescription (index date). OAAP persistence was measured allowing for a < 60-day gap. All-cause and schizophrenia-related inpatient and emergency department (ED) resource utilization during the follow-up period were compared between OAAP persistent and non-persistent groups.Results: The study sample of 13,007 had an average age of 39.1 years and 57.0% were male. Patients were persistent with their index OAAP for 135 days on average and 73.1% had a ≥ 60-day gap in antipsychotic therapy post-index. While 32.8% and 28.6% of patients who did not persist with their index OAAP restarted the index OAAP or switched to a different OAAP medication later in the year, respectively, a larger proportion (38.6%) had no further OAAP prescriptions. After adjustment for demographic and clinical variables, compared to non-persistent patients, persisting with OAAPs was significantly associated with fewer all-cause and schizophrenia-related hospitalizations (Incidence Rate Ratio [IRR]=0.742, p< 0.001; IRR=0.823, p< 0.001; respectively) and ED visits (IRR=0.759, p< 0.001; IRR=0.773, p< 0.001; respectively).Conclusion: Non-persistence with OAAP medication is common among patients with schizophrenia and associated with negative outcomes including increased utilization of hospital and ED resources. Patient-centered interventions that improve antipsychotic persistence should be implemented to facilitate optimal outcomes in this population.Keywords: antipsychotic medication, persistence, healthcare resource utilization, Medicaid, schizophrenia

ObjectivesAntipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescribed APS.Experimental designThe observational analysis used baseline, cross-sectional data from 16 international studies for adults aged ≥ 50 years with BD comprising 1,007 individuals with mean age 63.2 years (SD = 9.0), 57.4% women, and mean age of onset 31.6 years (SD = 15.0). The dependent variable was current APS treatment status. The independent variables included demographic and clinical variables, and a random effect for study, that were included in generalized mixed models.Principal observations46.6% of individuals (n = 469) were using APS. The multivariate model results suggest that those treated with APS were younger (p = 0.01), less likely to be employed (p < 0.001), had more psychiatric hospitalizations (p = 0.009) and were less likely to be on lithium (p < 0.001). Of individuals on APS, only 6.6% of those (n = 27) were on first-generation antipsychotics (FGAs) and experienced a greater burden of psychiatric hospitalizations (p = 0.012).ConclusionsAPS are widely prescribed in OABD, observed in nearly half of this sample with great variation across sites. Individuals with OABD on APS have more severe illness, more frequent hospitalizations and are more often unemployed vs. those not on APS. Future studies need to examine longitudinal outcomes in OABD prescribed APS to characterize underlying causal relationships.

Schizophrenia is a mental health condition that disrupts several different areas of the brain. This condition typically affects thinking abilities, memories, and senses. Antipsychotic medications and maintenance-electroconvulsive therapy (m-ECT) are the cornerstone of schizophrenia treatment. This case report focuses on a 21-year-old woman with Schizophrenia on m-ECT and antipsychotic medication. Her symptoms did not subside with drug therapy and she was started with m-ECT. Five ECT sessions were given to her with antipsychotic medication. The patient's mood, appearance, behaviour, perception and self-care improved after m-ECT. As a result of the collaboration between the clinical pharmacists and the multidisciplinary team in the management of the patient, her insight improved eventually. Literature collected from various countries (UK, Poland, Japan, Korea, USA and Malta) stated that schizophrenia can be successfully treated with m-ECT. We discuss the importance of recognizing and treating the patient with schizophrenia with antipsychotic medication and m-ECT. There is a need for further research on the correlation between schizophrenia on m-ECT and drug therapy in young adults. [ABSTRACT FROM AUTHOR]

Introduction and purpose Cariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use. Methods and materials A review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist. Conclusions Cariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.

Background: Schizophrenia is a major psychiatric disorder affecting physical, psychosocial, and cognitive functioning. Treatment includes pharmacological and psychotherapeutic interventions. Adherence to prescribed medication is critical but reportedly low, because of side effects, failure to understand instructions, a lack of insight about the condition, cognitive deficits, and financial difficulties. Interventions to promote adherence to medication are required. This study introduced a treatment buddy to provide the patient with virtual support in adherence to medication. Aim: The aim of this study was to explore the participants’ lived experiences of a treatment buddy support. Setting: A specialised psychiatric clinic in a resource-constrained district of KwaZulu-Natal, South Africa. Methods: A qualitative study design, using semi-structured one-on-one interviews, was used to collect in-depth data from 24 participants, suffering from schizophrenia and who had been offered virtual treatment buddy support for 6 months. Data were analysed using thematic analysis. Results: The intervention improved adherence to medication. Participants indicated that the text messages served as reminders to take their medication daily. An alleviation of associated problems such as sleeping difficulties was observed. Participants were willing to encourage other patients suffering from schizophrenia to join ‘treatment buddy services’. Conclusion: The virtual treatment buddy support increased awareness of the importance to adhere to antipsychotic medications among patients suffering from schizophrenia and helped to resolve other schizophrenia-related problems experienced by the participants. Contribution: The study has provided a supportive intervention that can be utilised by mental health institutions to address poor adherence to medication by patients suffering from schizophrenia.

Background: Severe mental illness is associated with higher physical health morbidities and reduced life expectancy, with an estimated 14.3% of global deaths attributed to mental disorders. Antipsychotic medications (APs) used in treatment contribute to physical health issues, including metabolic and cardiovascular effects. Aim: The aim of this study was to assess nurses’ practices regarding metabolic monitoring for patients prescribed antipsychotic medications at Mohlomi Hospital in Lesotho. Setting: The study was conducted at Mohlomi Hospital, the primary psychiatric facility in Lesotho. Methods: Using a cross-sectional design, 44 nurses from Mohlomi Hospital participated in the study. A structured questionnaire assessed nurses’ metabolic monitoring practices. Results: Most of the respondents were female (n = 30, 75%), and minority were male (n = 10, 25%). The academic qualifications of respondents were distributed as follows: 40% (16) held a nursing assistant certificate and 22.5% (9) held an advanced nursing diploma, among others. The average age of all respondents was 39.05 (s.d. 8.9), with an average of 8 years of experience in psychiatry (s.d. 7.6). The overall rate of nurses’ practices of metabolic monitoring for patients taking antipsychotic medications showed variability, with a mean score of 2.83 (s.d. 0.524). However, only 20% performed ECG tests, 22.5% measured blood pressure, 27.5% tested for glucose abnormalities and 17.5% conducted lipid profile testing. Conclusion: Results revealed a significant gap in the practice of metabolic monitoring among nurses with various aspects of metabolic monitoring, not being adequately monitored. Contribution: The study’s findings shall inform policy and guidelines for monitoring patients on antipsychotic medications while guiding future research.

Abstract Aim This study aimed to identify atypical hubs in the whole‐brain networks of patients with schizophrenia (SZ) and examine the effects of antipsychotic medications, using electroencephalography (EEG) data. Methods We estimated the functional connectivity across all electrodes by applying the phase lag index to the EEG signals of 21 drug‐naïve patients with SZ and 31 age‐matched healthy controls. Betweenness centrality (BC), a measure of hub status, was calculated for each electrode and frequency band. Data from 14 patients were re‐evaluated after initiating treatment with antipsychotic medications. Results BC values decreased significantly at the Fz site in the beta band, decreased significantly at Pz in the gamma band, and increased significantly at O1 in the gamma band among patients with SZ. These changes persisted after antipsychotic treatment and were unrelated to clinical symptoms. Conclusion The abnormal hub topology we observed, especially in the high‐frequency band, may reflect the pathophysiology of SZ, and this study highlights the utility of BC analysis of EEG data for detecting alterations in the whole‐brain networks of patients with SZ.

Background: Schizophrenia is a major psychiatric disorder affecting physical, psychosocial, and cognitive functioning. Treatment includes pharmacological and psychotherapeutic interventions. Adherence to prescribed medication is critical but reportedly low, because of side effects, failure to understand instructions, a lack of insight about the condition, cognitive deficits, and financial difficulties. Interventions to promote adherence to medication are required. This study introduced a treatment buddy to provide the patient with virtual support in adherence to medication. Aim: The aim of this study was to explore the participants' lived experiences of a treatment buddy support. Setting: A specialised psychiatric clinic in a resource-constrained district of KwaZulu-Natal, South Africa. Methods: A qualitative study design, using semi-structured one-on-one interviews, was used to collect in-depth data from 24 participants, suffering from schizophrenia and who had been offered virtual treatment buddy support for 6 months. Data were analysed using thematic analysis. Results: The intervention improved adherence to medication. Participants indicated that the text messages served as reminders to take their medication daily. An alleviation of associated problems such as sleeping difficulties was observed. Participants were willing to encourage other patients suffering from schizophrenia to join 'treatment buddy services'. Conclusion: The virtual treatment buddy support increased awareness of the importance to adhere to antipsychotic medications among patients suffering from schizophrenia and helped to resolve other schizophrenia-related problems experienced by the participants. Contribution: The study has provided a supportive intervention that can be utilised by mental health institutions to address poor adherence to medication by patients suffering from schizophrenia. [ABSTRACT FROM AUTHOR]

Antipsychotic medications increase the risk of abnormal glucose metabolism. However, in clinical practice, it is difficult to predict this risk because it is affected by medication-related and background factors. This study aimed to identify the risk factors for abnormal glucose metabolism during antipsychotic treatment. We conducted a multicenter, prospective, cohort study in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Of these patients, those with prediabetes or possible diabetes were excluded. Finally, 706 patients were included in the analysis. The hazard ratio (HR) for each factor was calculated for events of progression to hyperglycemia using time-dependent Cox regression analysis stratified according to facility type and adjusted for available background and drug-related factors. Treatments with olanzapine (HR = 2.06, 95% confidence interval [CI] = 1.05–4.05), clozapine (HR = 4.25, 95% CI = 1.56–11.60), and chlorpromazine (HR = 4.48, 95% CI = 1.21–16.57), overweight and obesity (HR = 1.57, 95% CI = 1.02–2.41), and hypertriglyceridemia (HR = 1.72, 95% CI = 1.02–2.88) were associated with a significantly higher occurrence of hyperglycemic progression. The number and daily dose of antipsychotics were not associated with their occurrence. Our study demonstrated that more careful monitoring is necessary during olanzapine, clozapine, and chlorpromazine treatment because of the higher occurrence of abnormalities in glucose metabolism. Furthermore, patients with obesity or hypertriglyceridemia warrant monitoring for the occurrence of abnormal glucose metabolism, regardless of the type of antipsychotic medication. • Treatment with olanzapine increased the incidence of hyperglycemic progression. • Treatment with clozapine increased the incidence of hyperglycemic progression. • Treatment with chlorpromazine increased the incidence of hyperglycemic progression. • Being overweight or obese affected the high incidence of hyperglycemic progression. • Raised triglycerides is associated with high incidence of hyperglycemic progression. [ABSTRACT FROM AUTHOR]

Abstract Objectives Decision aids (DAs) are promising tools to foster evidence‐based shared decision‐making between practitioners and service users. Nevertheless, it is still obscure how an evidence‐based DA for people with severe mental illness, especially psychosis, should look in an inpatient treatment setting to be useful and feasible. Therefore, we conducted focus groups with psychiatrists and service users to collect and assess their expectations and wishes regarding an evidence‐based DA. From these findings, we derived immediate recommendations for the future development of DAs. Methods We held two group interviews with service users (n = 8) and three group interviews with psychiatrists (n = 10). We used an open, large‐scale topic guide. First, we presented data from a current meta‐analysis on antipsychotics to the interviewees and, in a second step, asked for their expectations and wishes towards a DA that integrates these data. Results Our thematic analysis revealed six key themes addressed by the respondents: (1) general considerations on the importance and usefulness of such a DA, (2) critical comments on psychiatry and psychopharmacotherapy, (3) communicative prerequisites for the use of a DA, (4) form and content of the DA, (5) data input, data processing and output as well as (6) application of the DA and possible obstacles. Conclusions Participants identified several important features for the development of DAs for selecting antipsychotics in inpatient psychiatric treatment. The digital format was met with the greatest approval. Especially the adaptability to different needs, users and psychopathologies and the possibility to outsource information dissemination via app seemed to be a decisive convincing argument. Further research is required to test specific features of DAs to be developed in clinical settings.

Abstract Background Predominant negative symptoms (PNSs) in schizophrenia can affect the patients’ psychosocial functioning immensely and are less responsive to treatment than positive symptoms. Aims The aim of the study was to observe negative symptoms and psychosocial functioning in PNS schizophrenia patients and to understand whether PNS can be improved and with what treatment strategies. Methods This was a 1-year, prospective, multicentric cohort study conducted in Slovakia. Adult outpatients with diagnosis of schizophrenia according to ICD-10 and PNS evaluated using the criteria by the European Psychiatric Association’s (EPA) guidance were included. Change in negative symptoms, functionality, and treatment patterns were observed. Treatment effectiveness was evaluated using the modified Short Assessment of Negative Domain (m-SAND), the Self-evaluation of Negative Symptoms (SNS) scale, the Personal and Social Performance (PSP) scale, and the Clinical Global Impression – Severity (CGI-S) and the Clinical Global Impression – Improvement (CGI-I) scales. Least-squares (LS) means were calculated for the change from baseline to final visit for the outcomes. Results The study included 188 patients. Functionality improved as, by the end of the study, fewer patients were unemployed (53%) and more worked occasionally (21%). PNS improved significantly according to both physicians and patients (LS mean change from baseline in m-SAND total score: -10.0 (p-value

Contemporary practices of long-term antipsychotic maintenance treatment for schizophrenia are being challenged, and clinicians must consider the possibilities of reducing long-term maintenance use. However, research indicates that people with schizophrenia receive little support from mental health staff to reduce antipsychotic medication. This article reports a study which aimed to investigate interdisciplinary mental health staff's accounts of tapering of antipsychotic medication and to explore different positions that mental health staff assign to themselves and others. Six focus groups were conducted with 39 mental health staff from outpatient clinics, inpatient units, forensic mental health units, and community mental health services. The data analysis combined analyses of the interactions during focus groups and the thematic content. Results were considered from a discourse analytic perspective considering the function and consequence of accounts applied by the mental health staff. The mental health staff accounted for their perspectives on tapering from the following three distinctive positions: 1) No, patients will eventually realize that they need the medication, 2) Yes, but tapering means running a big risk of relapse in symptoms, and 3) Yes, we need to welcome risks to support personal recovery. Our findings indicated that there was reluctance among interdisciplinary mental health staff to let service users make decisions and limited possibilities for people with schizophrenia to have their request for tapering of their antipsychotic medication met by mental health staff. [ABSTRACT FROM AUTHOR]

Background: It has been reported that coronavirus disease 2019 (COVID-19) may cause psychiatric disorders, but there are too many confounding factors in the various studies, making it difficult to draw accurate conclusions. Methods: We analyzed the clinical features and treatment of patients with non-severe COVID-19 who were hospitalized in neurology and psychiatry departments due to acute psychiatric disorders and performed a descriptive analysis. Results: Of the 57 patients included, 65% were hospitalized in the neurology department. Eighty-two percent of the patients exhibited abnormal mental behavior 1 week or less after COVID-19 diagnosis, and more than 60% of the patients had normal electroencephalogram (EEG), head imaging, autoimmune encephalitis antibody, and cerebrospinal fluid (CSF) results. Abnormal EEG results included an increase in nonspecific slow waves, abnormal imaging results included small ischemic areas and lacunar infarctions, and abnormal CSF results included a slight increase in cell numbers and protein levels and an increase in pressure. After administering antipsychotic drugs and/or immunotherapy, 67% of the patients experienced improvement in their psychiatric disorders by the time of discharge. Thirty-nine percent of the patients were discharged without antipsychotic medication and experienced no relapse of psychiatric symptoms. Conclusion: Patients with non-severe COVID-19 and psychiatric disorders usually have a good prognosis and do not require long-term antipsychotic medication. Patients with uncontrollable mental symptoms experienced rapid remission after immunotherapy, suggesting that inflammation or the immune response may play an important role in the occurrence of simple acute psychiatric disorders caused by COVID-19. [ABSTRACT FROM AUTHOR]

Purpose of Review: Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia spectrum disorders (SSD) do not differentiate between men and women. This review summarizes the available evidence on strategies that may improve pharmacotherapy for women and provides evidence-based recommendations to optimize treatment for women with schizophrenia. Recent Findings: We systematically searched PubMed and Embase for peer-reviewed studies on three topics: (1) sex differences in dose-adjusted antipsychotic serum concentrations, (2) hormonal augmentation therapy with estrogen and estrogen-like compounds to improve symptom severity, and (3) strategies to reduce antipsychotic-induced hyperprolactinemia. Based on three database studies and one RCT, we found higher dose-adjusted concentrations in women compared to men for most antipsychotics. For quetiapine, higher concentrations were specifically found in older women. Based on two recent meta-analyses, both estrogen and raloxifene improved overall symptomatology. Most consistent findings were found for raloxifene augmentation in postmenopausal women. No studies evaluated the effects of estrogenic contraceptives on symptoms. Based on two meta-analyses and one RCT, adjunctive aripiprazole was the best-studied and safest strategy for lowering antipsychotic-induced hyperprolactinemia. Summary: Evidence-based recommendations for female-specific pharmacotherapy for SSD consist of (1) female-specific dosing for antipsychotics (guided by therapeutic drug monitoring), (2) hormonal replacement with raloxifene in postmenopausal women, and (3) aripiprazole addition as best evidenced option in case of antipsychotic-induced hyperprolactinemia. Combining these strategies could reduce side effects and improve outcome of women with SSD, which should be confirmed in future longitudinal RCTs. [ABSTRACT FROM AUTHOR]

Background and hypothesis Several studies suggest that raloxifene, a selective estrogen receptor modulator, improves symptoms and cognition in post-menopausal women with Schizophrenia-Spectrum Disorders (SSD). We aimed to assess the effects of adjunctive raloxifene in women and men with SSD. Study design This parallel, randomized, double-blind, placebo-controlled trial included adult SSD patients across the Netherlands and Belgium. Participants were stratified by age, sex, and global functioning and randomly assigned 1:1 to 12-week add-on raloxifene or placebo. Primary outcomes were symptom severity at 6, 12, and 38 weeks and cognition at 12 and 38 weeks, as measured with the Positive and Negative Syndrome Scale and the Brief Assessment of Cognition in Schizophrenia, respectively. Intention-to-treat analyses were performed using linear mixed-effect models. Study results We assessed 261 patients for eligibility, of which 102 (28% female) were assigned to raloxifene (n  = 52) or placebo (n  = 48). Although we found no main effect of raloxifene, secondary sex-specific analysis showed that in women, raloxifene had beneficial effects on negative symptoms at week 6 (LSM −2.92; adjusted P  = 0.020) and week 12 (LSM −3.12; adjusted P  = 0.030), and on working memory at week 38 (LSM 0.73; adjusted P  = 0.040), while having negative effects on working memory at week 38 in men (LSM −0.53; adjusted P  = 0.026). The number of adverse events was similar between groups. Conclusions Our results do not support the use of raloxifene in patients with SSD in general, but suggest female-specific beneficial effects of raloxifene on negative symptoms and working memory. Our findings encourage further research on sex-specific pharmacotherapeutic treatment. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic medications (APMs) have been used to treat multiple psychiatric disorders for decades. The conditions to use these medications have expanded from primarily psychotic disorders to Food and Drug Administration--approved uses as first-line mood stabilizers in bipolar disorder and adjunctive pharmacotherapy in unipolar depression. Antipsychotic medications can have serious side effects, including drug-induced movement disorders (DIMDs). Nurse practitioners (NPs) in non--psychiatric-mental health specialties are increasingly managing psychotropic medication regimes. There is a void in peer-reviewed literature capturing the scope of NPs managing APMs, such as whether they received training to prescribe and manage risks of APM, and if so, what type (e.g., continuing education, attending conferences, consulting), and their confidence assessing and managing DIMDs. Purpose: To describe the scope of NP management, knowledge, and confidence related to APMs and associated risks of DIMDs. Methodology: Nonexperimental, descriptive, cross-sectional survey. Participants (n = 400) recruited through a professional association membership portal. Results: Nearly two-thirds of participants reported managing APMs (64%) and receiving training to prescribe and manage risks of APMs (63%). More than half (54%) reported they received training to do so in their NP education program. Thirty-five percent of participants indicated they were either completely (6%) or fairly (29%) confident, whereas most (65%) endorsed being somewhat (26%), slightly (20%), or not (19%) confident in assessing and managing DIMDs. Conclusions/Implications: Opportunities exist to broaden NP education in managing APMs and associated risks of DIMDs. [ABSTRACT FROM AUTHOR]

Pharmacists have a contribution to make in improving optimising medication use for people on antipsychotic medication. The rates of prescribing antipsychotics have increased in England with an 18% rise from 2015 to 2020. People on antipsychotic medication are not treated as equal partners in conversations about their medications. This can leave people to make decisions about their antipsychotic medications without input from their prescribers which can have significant consequences for individuals. Involving people in the decision-making process, as experts on their own condition, has the potential to improve treatment outcomes. The evidence suggests that involving pharmacists in supporting people with serious mental illnesses will lead to improved clinical outcomes. Key areas for pharmacist involvement are providing information, education and counselling on antipsychotic medication and the side effects and reducing polypharmacy especially when antipsychotics are prescribed off license. [ABSTRACT FROM AUTHOR]

IntroductionResearch examining the role of inflammation in psychosis has produced inconsistent results. Variables that influence inflammation, including antipsychotic medication, are inconsistently controlled across studies and variation of inflammatory analytes across stages of psychosis may also influence findings. The purpose of this study was to assess for evidence of immuno-inflammatory dysregulation across the stages of early psychosis. We examined a immuno-inflammatory analytes in subjects at clinical high risk (CHR) for developing a psychotic disorder, antipsychotic-naïve (-n) and antipsychotic treated (-a) subjects in their first episode of psychosis (FEP), and healthy control (HC) subjects.MethodsA total of 11 subjects at CHR, 50 subjects within their FEP (40 FEP-n, 10 FEP-a), and 10 HC subjects were recruited from early psychosis programs in San Diego and Mexico City. Plasma was collected for biomarker assay.ResultsImmuno-inflammatory analytes significantly differed between groups: Interferon-gamma (IFN-γ), Interleukin-10 (IL-10), Eotaxin-1, Interferon Gamma-Induced Protein-10 (IP-10), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage-Derived Chemokine (MDC), Macrophage Inflammatory Protein-1 beta (MIP-1β), Thymus and Activation Regulated Chemokine (TARC), and Brain Derived Neurotropic Factor (BDNF). Post-hoc analyses revealed an overall pattern of higher levels of IL-10, MCP-1, MIP-1β, TARC, and BDNF in CHR as compared to FEP-a, FEP-n, and HC subjects.ConclusionsResults reveal a profile of immuno-inflammatory dysregulation in early stages of psychosis prior to psychotic conversion and treatment with antipsychotic medication. The CHR phase of early psychosis may represent a period of increased immuno-inflammatory activation, but due to limited sample size, these results deserve replication in a well characterized early psychosis population.

Background: Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non‐medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids. Methods: This study utilized data from a triple‐blind randomized placebo‐controlled trial comparing two groups of antipsychotic‐naïve young people with a FEP who were randomized to receive a second‐generation antipsychotic medication (FEP‐medication group) or placebo (FEP‐placebo group) for 6 months. Twenty‐seven control participants were also recruited. Results: Eighty‐one participants commenced the trial; 69.1% completed at least 3 months of the intervention and 33.3% completed the full 6 months. The FEP‐placebo group gained a mean of 2.4 kg (±4.9) compared to 1.1 kg (±4.9) in the control participants (t = 0.76, p =.45). After controlling for multiple analyses, there was no difference in blood pressure, waist circumference or heart rate between the FEP‐placebo group and controls. After 6 months, the FEP medication group had gained 4.1 kg (±4.5), higher than those receiving placebo but not statistically significant (t = 0.8, p =.44). There were no differences in fasting glucose or lipids between the FEP groups after 3 months. Conclusions: While limited by small numbers and high attrition, these findings indicate that some of the metabolic complications observed in psychotic disorders could be attributable to factors other than medication. This emphasizes the need to deliver physical health interventions early in the course of FEP. [ABSTRACT FROM AUTHOR]

Objectives: Decision aids (DAs) are promising tools to foster evidence‐based shared decision‐making between practitioners and service users. Nevertheless, it is still obscure how an evidence‐based DA for people with severe mental illness, especially psychosis, should look in an inpatient treatment setting to be useful and feasible. Therefore, we conducted focus groups with psychiatrists and service users to collect and assess their expectations and wishes regarding an evidence‐based DA. From these findings, we derived immediate recommendations for the future development of DAs. Methods: We held two group interviews with service users (n = 8) and three group interviews with psychiatrists (n = 10). We used an open, large‐scale topic guide. First, we presented data from a current meta‐analysis on antipsychotics to the interviewees and, in a second step, asked for their expectations and wishes towards a DA that integrates these data. Results: Our thematic analysis revealed six key themes addressed by the respondents: (1) general considerations on the importance and usefulness of such a DA, (2) critical comments on psychiatry and psychopharmacotherapy, (3) communicative prerequisites for the use of a DA, (4) form and content of the DA, (5) data input, data processing and output as well as (6) application of the DA and possible obstacles. Conclusions: Participants identified several important features for the development of DAs for selecting antipsychotics in inpatient psychiatric treatment. The digital format was met with the greatest approval. Especially the adaptability to different needs, users and psychopathologies and the possibility to outsource information dissemination via app seemed to be a decisive convincing argument. Further research is required to test specific features of DAs to be developed in clinical settings. Patient or Public Contribution: The entire project is supported by an advisory board, including also experienced users. The members are regularly updated about the process and give important feedback. [ABSTRACT FROM AUTHOR]

Abstract Background More than half of people who use antipsychotic medication for psychosis report having sexual dysfunction. The REMEDY trial aimed to find out if switching antipsychotic medication provides an effective way to reduce sexual dysfunction among people with psychosis. We set out to recruit 216 participants over a two-year period, but recruitment was stopped after an extended 12-month pilot phase, during which we recruited only 10 participants. As part of a nested process evaluation, we conducted qualitative interviews with front-line clinicians to examine barriers to recruitment to the trial. Methods We developed a semi-structured interview schedule to explore staff views on factors that influenced whether they referred potential participants to the study. We interviewed a purposive sample of 51 staff from four National Health Service (NHS) Trusts in England, ensuring a range of different backgrounds, seniority, and levels of involvement in the trial. Audio recordings of interviews were transcribed for verbatim, and data were analysed using an inductive approach to thematic analysis. Results Nine interconnected themes were generated. Six themes concerned barriers to recruitment; including; prioritising patients’ mental stability, mutual discomfort and embarrassment about discussing a “taboo” subject, and concerns about unintended consequences of asking people with psychosis about their sexual functioning. Three themes, including the quality of treatment relationships and strategies for opening dialogue suggested ways to improve recognition of these “hidden” side effects. Conclusion The identification and management of sexual dysfunction among people with psychosis are not priorities for mental health services in England at this time. Many staff working in front-line services feel unprepared and uncomfortable asking people with psychosis about these problems. While greater use of screening tools may improve the identification of sexual dysfunction among people with psychosis, the evaluation and implementation of interventions to manage them will continue to be challenging unless NHS leaders and senior clinicians demonstrate greater commitment to changing current clinical practice. Trial registration Current Controlled Trials ISRCTN12307891.

Diabetes mellitus is a sequelae of antipsychotic medication in people of Indian descent with schizophrenia. The Indian socio-cultural context amplifies challenges of managing chronic illness. The aim of this study was to explore Indian mental health service users’ perspectives of managing comorbid psychosis and diabetes mellitus, specifically culture-related difficulties.In this exploratory study, people with an Indian cultural background recruited from community mental health clinics were interviewed by an Indian psychiatrist using a semi-structured questionnaire. Interviews were professionally transcribed. Reflexive thematic analysis was used to develop central organising concepts and identify themes.Four themes were identified: culture-specific views on comorbidity, preferences for tailoring education to Indian language and culture, changes in interpersonal relationships within extended family and relationships with healthcare professionals. Advice from hospital services was not specific to Indian culture and there were wider impacts of illness for wider family.Indian New Zealanders have challenges in managing dual mental and physical illnesses. Further research is needed to develop approaches to care that emphasise service users’ culture as core to understanding illness and treatment. This includes consideration of gender roles, families, communities, food, language, lifestyle and barriers to treatment. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) patients show aberrant white matter microstructure compared to healthy controls but little is known about the relation with clinical characteristics. We therefore investigated the relation of white matter microstructure with the main pharmacological treatments as well its relation with IQ. Patients with BD (N = 257) and controls (N = 167) underwent diffusion tensor imaging (DTI) and comprehensive clinically assessments including IQ estimates. DTI images were analyzed using tract-based spatial statistics. Fractional anisotropy (FA) and Mean Diffusivity (MD) were determined. Patients had significantly lower FA and higher MD values throughout the white matter skeleton compared to controls. Within the BD patients, lithium use was associated with higher FA and lower MD. Antipsychotic medication use in the BD patients was not associated with FA but, in contrast to lithium, was associated with higher MD. IQ was significantly positively correlated with FA and negatively with MD in patients as well as in controls. In this large DTI study we found evidence for marked differences in FA and MD particularly in (but not restricted to) corpus callosum, between BD patients and controls. This effect was most pronounced in lithium-free patients, implicating that lithium affects white matter microstructure and attenuates differences associated with bipolar disorder. Effects of antipsychotic medication intake were absent in FA and only subtle in MD relative to those of lithium. The abnormal white matter microstructure was associated with IQ but not specifically for either group.

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Introduction: This reviews aim was to explore the evidence base for the use of antipsychotic medications in the management of acute symptoms in patients with emotionally unstable personality disorder. Methods: Relevant databases and grey literature were searched for relevant papers. Inclusion/exclusion criteria were applied which resulted in the retrieval of eight papers pertinent to the literature review. The papers were critically appraised, and a thematic analysis was undertaken to collate relevant data. Findings: Five themes emerged from this literature review: different outcome measures, symptom domains (anger, impulsivity, mood instability, pseudopsychotic symptoms, self-harm and suicidal behaviours, adverse effects, the quality of the evidence and bias). Conclusions: The evidence base is not robust enough to allow conclusions to be drawn. Any positive results must be weighed up against the potential for adverse events. This review lays the foundations for further research, which is needed to explore antipsychotic treatment. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition emerging in early childhood, characterized by core features such as sociocommunicative deficits and repetitive, rigid behaviors, interests, and activities. In addition to these, disruptive behaviors (DB), including aggression, self-injury, and severe tantrums, are frequently observed in pediatric patients with ASD. The atypical antipsychotics risperidone and aripiprazole, currently the only Food and Drug Administration-approved treatments for severe DB in patients with ASD, often encounter therapeutic failure or intolerance. Given this, exploring pharmacological alternatives for more effective management of DB associated with ASD is essential. Clozapine, noted for its unique antiaggressive effects in schizophrenia and in various treatment-resistant neuropsychiatric disorders, independent from its antipsychotic efficacy, remains underexplored in youths with ASD facing severe and persistent DB., Objective: This study aimed to evaluate the efficacy, tolerability, and safety of clozapine for treatment-resistant DB in youths with ASD., Methods: This is a prospective, single-center, noncontrolled, open-label trial. After a cross-titration phase, 31 patients with ASD aged 10-17 years and with treatment-resistant DB received a flexible dosage regimen of clozapine (up to 600 mg/day) for 12 weeks. Standardized instruments were applied before, during, and after the treatment, and rigorous clinical monitoring was performed weekly. The primary outcome was assessed using the Irritability Subscale of the Aberrant Behavior Checklist. Other efficacy measures include the Clinical Global Impression Severity and Improvement, the Swanson, Nolan, and Pelham questionnaire-IV, the Childhood Autism Rating Scale, and the Vineland Adaptive Behavior Scale. Safety and tolerability measures comprised adverse events, vital signs, electrocardiography, laboratory tests, physical measurements, and extrapyramidal symptoms with the Simpsons-Angus Scale. Statistical analysis will include chi-square tests with Monte Carlo simulation for categorical variables, paired t tests or Wilcoxon tests for continuous variables, and multivariate linear mixed models to evaluate the primary outcome, adjusting for confounders., Results: Recruitment commenced in February 2023. Data collection was concluded by April 2024, with analysis ongoing. This article presents the protocol of the initially planned study to provide a detailed methodological description. The results of this trial will be published in a future paper., Conclusions: The urgent need for effective pharmacological therapies in mitigating treatment-resistant DB in pediatric patients with ASD underscores the importance of this research. Our study represents the first open-label trial to explore the anti-aggressive effects of clozapine in this specific demographic, marking a pioneering step in clinical investigation. Adopting a pragmatic approach, this trial protocol aims to mirror real-world clinical settings, thereby enhancing the applicability and relevance of our findings. The preliminary nature of future results from this research has the potential to pave the way for more robust studies and emphasize the need for continued innovation in ASD treatment., Trial Registration: Brazilian Clinical Trials Registry RBR-54j3726; https://ensaiosclinicos.gov.br/rg/RBR-54j3726., International Registered Report Identifier (irrid): DERR1-10.2196/58031., (©André Luiz Schuh Teixeira da Rosa, Marina Ribeiro Barreto da Costa, Gabriela Bezerra Sorato, Felipe de Moura Manjabosco, Érica Bonganhi de Bem, Lucas Dellazari, Arthur Bezerra Falcão, Lucas de Oliveira Cia, Olivia Sorato Bezerra, Rogério Boff Borges, Luis Augusto Rohde, Ana Soledade Graeff-Martins. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.01.2025.)

The perspective article explores systemic issues in psychiatric care, particularly the barriers to timely treatment and the ethical dilemmas involved in involuntary interventions. It further examines the impact of anosognosia-lack of disease insight-on treatment, noting the difficulties in managing care for those unaware of their illness, and scrutinizes training materials from international organizations that might mislabel necessary psychiatric practices as human rights violations, thereby complicating the care landscape. The discussion extends to the legal and societal implications of psychiatric interventions, using Massachusetts' Rogers Guardianship as a case study to highlight the consequences of legalistic approaches to mental health treatment.The article calls for destigmatizing psychiatric treatment and integrating robust, evidence-based practices to improve patient outcomes and healthcare equity. The global mental health policy landscape is urged to recognize the critical role of psychiatric care in restoring health and dignity to individuals with serious mental illnesses, advocating for a more nuanced understanding and application of human rights in mental health.

Arturas Kalniunas,1 Ipsita Chakrabarti,1 Rakhee Mandalia,1 Jasna Munjiza,2,3 Sofia Pappa1,2 1West London NHS Trust, London, UK; 2Division of Psychiatry, Imperial College London, London, UK; 3Central and North West London NHS Foundation Trust, London, UKCorrespondence: Sofia PappaRecovery Team East, Avenue House, 43-47 Avenue Road, London, W3 8NJ, UKEmail sofia.pappa@westlondon.nhs.uk; s.pappa@imperial.ac.ukObjective: We aim to systematically review evidence for a relationship between antipsychotic-induced akathisia and suicidal behaviour, in order to guide further clinical decision making in this area.Methods: Several electronic databases (Embase, Medline, Cochrane and PsychINFO) were systemically searched for articles published up to February 2021, using search terms related to akathisia, antipsychotics and suicidal behaviour. Two reviewers independently evaluated all the relevant studies using predetermined criteria and assessed the risk of bias for each included study. The systematic review was conducted in line with PRISMA methodology and reporting.Results: Following de-duplication, screening and application of exclusion criteria, four eligible studies were identified. All of the available studies were in English and included adult patients. Nevertheless, there was significant variability regarding methodology and overall quality was deemed low due to small sample sizes. There was insufficient data to perform statistical analyses of the results. Of the four studies, two found a weak correlation between antipsychotic-related akathisia and suicidal behaviour, a finding that was not supported by the remaining two studies.Conclusion: The search yielded very few studies for inclusion. On the basis of the existing evidence, akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication. However, proactive screening for emerging suicidal behaviour in this vulnerable patient group is advisable. Our findings highlight the pressing need for further research in this area.Keywords: antipsychotic medication, akathisia, restlessness, suicidal behaviour