C-Reactive Protein (CRP): A Potent Inflammation Biomarker in Psychiatric Disorders.

An increasing number of studies have investigated the role of inflammation in psychiatric disorders, by demonstrating how an altered/dysfunctional immunological and inflammatory system may underpin a psychiatric condition. Particularly, several studies specifically investigated the role of a neuroinflammatory biomarker, named C-reactive protein (CRP), in psychiatric disorders. Overall, even though scientific literature so far published still does not appear definitive, CRP is more likely reported to be elevated in several psychiatric disorders, including schizophrenia, mood disorders, anxiety disorders and post-traumatic stress disorder. Moreover, a low-grade inflammation (CRP >3 mg/L) has been more likely observed in a subgroup of patients affected with a more severe psychopathological symptomatology, more treatment resistance and worst clinical mental illness course, strengthening the hypothesis of the need for a different clinical and prognostic characterization based on this concomitant neuroinflammatory predisposition. However, even though further research studies are needed to confirm this preliminary evidence, CRP may represent a potential clinical routine biomarker which could be integrated in the clinical routine practice to better characterize clinical picture and course as well as address clinicians towards a personalized treatment.

Cognitive and negative symptoms in schizophrenia with L-Carnosine adjuvant therapy - A randomized double-blind placebo-controlled study.

The antioxidant L-Carnosine is reported to improve negative and cognitive symptoms in Schizophrenia. A randomized double-blind placebo-controlled study was planned to study the effectiveness of adjuvant L-Carnosine therapy in patients with Schizophrenia. 100 eligible patients with predominant negative symptoms as measured by scale for assessment of negative symptoms (SANS total score ≥ 60) and Schizophrenia diagnosis (International Classification of Disorder-Tenth Edition, ICD-10) were recruited. They were randomly allocated to receive a fixed dose of either 400 mg L-Carnosine or identical placebo for 3 months and increased to 800 mg from 13th week till completion of study. Primary outcome measures assessed changes in SANS scores with L-Carnosine at 24 weeks compared to baseline, 4 and 12 weeks. Secondary outcome measures were done to assess the improvement in cognitive symptoms (executive function, attention, and memory) at 24 weeks using subtests of NIMHANS (National Institute for Mental Health and Neurosciences) cognitive battery. Side effects were assessed using adverse events reporting form. The attention scores (p = .023) showed significant differences in patients receiving 800 mg of L-Carnosine at the end of the study. There were no significant differences in negative symptoms in the two arms at study completion. L-Carnosine dosing of 800 mg may be a promising agent to enhance executive functions in Schizophrenia.

A case of schizophrenia with relapsed catatonia successfully treated with blonanserin transdermal patch.

BACKGROUND: Catatonia is a syndrome that may present with stupor, immobility, and postural retention, and appears in various primary disorders including schizophrenia, depressive disorders, and neurodevelopmental disorders. CASE PRESENTATION: In this report, we describe a 34-year-old female patient with schizophrenia, who had previously been treated with antipsychotic agents to improve psychotic symptoms with delusional symptoms and catatonia. However, she relapsed with catatonic symptoms around 1 year after she voluntarily discontinued the prescribed antipsychotic medications by herself. Her catatonia was successfully improved using the transdermal blonanserin patch, a drug formulation globally first approved in Japan in 2019. DISCUSSION: Although benzodiazepines or electroconvulsive therapy have been recommended as the first-line treatment of catatonic manifestation observed in psychiatric patients, this patient responded well to antipsychotic blonanserin. From the differential drug responses, catatonia may be the complex of heterogeneous conditions with different pathophysiologies.

Psychotic Disorders in the Elderly: Diagnosis, Epidemiology, and Treatment.

This review covers the latest advances in our understanding of psychosis in the elderly population with respect to diagnosis, epidemiology, and treatment. Major topics of discussion include late life psychiatric disorders such as schizophrenia, schizoaffective disorder, and delusional disorder as well as dementia-related psychosis. Clinical differences between early-onset and late-onset disorders are reviewed in terms of prevalence, symptomatology, and approach to treatment. Newly revised research and clinical criteria for dementia-related psychosis are referenced. The evidence base for emerging therapies including citalopram and pimavanserin in relation to conventional therapies such as atypical antipsychotics are discussed..

Lessons from the coronavirus disease 2019 pandemic in schizophrenia: a review.

PURPOSE OF REVIEW: Multiple countries have reported increased COVID-19 mortality in patients with schizophrenia. The purpose of this review was to synthetize the consequences of the pandemic on patients with schizophrenia including vaccination data. RECENT FINDINGS: We have synthetized data on the increased risk of infection and increased mortality, the impact of the pandemic and lockdowns on psychiatric care, vaccination policies, unwillingness to vaccine in patients and the rates of vaccination. SUMMARY: Schizophrenia has been confirmed at increased risk of both COVID-19 infection and developing a severe/lethal form of the infection. Patients with schizophrenia should, therefore, be prioritized for vaccination whenever possible and should be prioritized for psychiatric and somatic care access. Psychotic symptomatology may be a barrier to vaccination in some patients, and heterogenous vaccination rates were identified in national databases. The COVID-19 pandemic has been also a unique opportunity to develop telehealth. A mixed face-to-face and distance model should be encouraged, whenever possible, to improve the experience of patients, relatives and healthcare professionals. No major change of long-acting antipsychotics has been reported in most countries, and there was no consistent evidence for clozapine prescription to increase the risk of COVID-19 infection or severe outcomes.

Antipsychotic Augmentation With N-Acetylcysteine for Patients With Schizophrenia.

N-acetylcysteine (NAC) augmentation of antipsychotic medication is one of very many antipsychotic augmentation strategies that have been studied in schizophrenia. A recent systematic review and meta-analysis of 6 randomized controlled trials (RCTs) found that NAC (median dose, 2,000 mg/d) improved several clinical outcomes at different time points with medium to large effect sizes; however, many of the significant findings in this meta-analysis are suspect because they appeared to be influenced by 2 short-term (8-week) RCTs with outlying characteristics. Important findings not influenced by the 2 outlying RCTs were significant attenuation by NAC of negative symptom (3 RCTs) and total psychopathology (2 RCTs) ratings at ≥ 24 weeks and improvement in working memory but not processing speed (3 RCTs). Of these findings, reduction in psychopathology ratings, though statistically significant, appeared too small to be clinically meaningful. Finally, a newly published, moderately large RCT of NAC (2,000 mg/d) in schizophrenia patients refractory to clozapine found that 1 year of treatment with NAC did not outperform placebo for any clinical, cognitive, or quality of life outcome. The take-home message is that it is premature to recommend the use of NAC to treat schizophrenia for any target domain in routine clinical practice and that there does not appear to be a role for NAC for any indication in clozapine-refractory schizophrenia. However, it may be worth studying whether NAC, dosed at 2,000 mg/d or higher for 6 months or longer, improves functional outcomes in schizophrenia.

Agitation in schizophrenia: origins and evidence-based treatment.

PURPOSE OF REVIEW: Agitation associated with schizophrenia remains an important clinical concern and if not managed effectively, can escalate into aggressive behavior. This is a review of the recent biomedical literature on agitation in individuals with schizophrenia. RECENT FINDINGS: Themes in the recent literature include consideration of comorbidities such as cigarette smoking and cannabis use. Surveys reveal that pharmacological approaches to manage agitation have changed little, with haloperidol remaining in common use and intramuscular administration of antipsychotics and/or benzodiazepines being frequently administered to more severely agitated/aggressive individuals. Of note, ketamine has been recently adopted for use in severe agitation in medical emergency departments, but the risk of this medication for people with schizophrenia is unclear. At present, inhaled loxapine remains the only rapidly acting noninjectable FDA-approved treatment for agitation associated with schizophrenia. In development is an intranasal formulation for olanzapine (a well characterized atypical antipsychotic already approved to treat agitation) and a sublingual film for dexmedetomidine (an α2-adrenergic agonist used as an anesthetic and now being repurposed). SUMMARY: Comorbidities can contribute to agitation and can make an accurate differential diagnosis challenging. The ongoing development of rapidly acting novel formulations of antiagitation medications, if successful, may facilitate clinical treatment by providing additional options.

Barriers to Long-acting Injectable Antipsychotic Adherence During the COVID-19 Pandemic: Observations From One Site.

OBJECTIVE: Long-acting injectable antipsychotics (LAI-As) are a crucial treatment option for individuals with serious mental illness. However, due to the necessity of in-person administration of LAI-As, pandemics pose unique challenges for continuity of care in the population prescribed these medications. This project investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on LAI-A adherence at a Veterans Health Administration medical facility in the United States, as well as changes in LAI-A prescribing and administration practices during this period. METHODS: Electronic health records were evaluated for 101 patients prescribed LAI-As. A subset of 13 patients also participated in an interview and rated subjective concerns about pandemic-related barriers to medication adherence. RESULTS: Pandemic-related barriers to LAI-A adherence and/or changes to LAI-A medications were documented in 33% of the patients. Within-subjects comparison of an adherence metric computed from electronic health record data further suggested a somewhat higher incidence of missed or delayed LAI-A doses during the pandemic compared with before the pandemic. In contrast, only 2 of the 13 patients interviewed anticipated that pandemic-related concerns would interfere with medication adherence. CONCLUSIONS: The results of this study suggest that LAI-A access and adherence can be disrupted by pandemics and other public health emergencies but this finding may not generalize to other sites. As patients may not foresee the potential for disruption, psychiatric service providers may need to assist in proactively problem-solving barriers to access. Improved preparedness and additional safeguards against pandemic-related disruptions to LAI-A access and adherence may help mitigate adverse outcomes in the future. Identifying patients at elevated risk for such disruptions may help support these efforts.

Long-acting Injectable Antipsychotics during the COVID-19 pandemic in schizophrenia: An observational study in a real-world clinical setting.

The COVID-19 pandemic is having an important impact on the practice of mental health services and on schizophrenia patients, and heterogeneous and conflicting findings are being reported on the reduction of long-acting injectable (LAI) antipsychotics use. Aims of the study were to assess the total number of patients treated with LAI, the start of novel LAI and the discontinuation of LAI treatments, analyzing register data of the first year of the pandemic, 2020, compared to a pre-pandemic reference year, 2019. Data from two outpatient centers were retrieved, for a total of 236 participants in 2020: no significant differences were observed comparing 2020 and 2019 when considering the total number of patients on LAI treatment (p = 0.890) and the number of dropouts (p = 0.262); however, a significant reduction in the start of LAI was observed (p = 0.022). In 2020, second generation LAI were more prescribed than first generation LAI (p = 0.040) while no difference was observed in 2019 (p = 0.191). These findings attest the efficacy of measures adopted in mental health services to face the consequences of COVID-19 and shed further light on the impact of the pandemic on the clinical practice of mental health services and on the continuity of care of people with schizophrenia.

Medication adherence among community-dwelling schizophrenia patients during the COVID-19 pandemic: A cross-sectional study.

OBJECTIVES: This study aims to investigate medication adherence during the COVID-19 pandemic among community-dwelling schizophrenia patients, and to explore the role of social support in improving medication adherence in a rural community sample in China. METHODS: A cross-sectional sample of 800 patients was recruited using a cluster random sampling method in Yingshan County, Sichuan Province. Information on participant demographic characteristics, social support and medication adherence was collected through face-to-face interviews. The data analysis was performed using SAS9.4. Two binary logistic regression models were employed to identify the association between regular medication use and social support. RESULTS: The rate of regular medication adherence among community-dwelling patients with schizophrenia was 41.5%,which was lower than that indicated by recent research(Li et al., 2020) before COVID-19 in western rural China. The mean scores and standard deviation of the patient's objective support, subjective support, and support utilization were 4.94 ± 1.57, 17.03 ± 5.24, and 5.25 ± 2.75, respectively. The social support standard deviation was 27.22 ± 6.32. The crude odds ratio of objective support, subjective support, and support utilization were 0.790 (95%CI:0.713-0.876), 0.999 (95%CI:0.971-1.027), and 1.049 (95%CI:0.995-1.105) respectively. After adjusting for potential factors, the adjusted odds ratio of objective support, subjective support, and support utilization were 0.758 (95%CI:0.673-0.853), 1.030 (95%CI:0.994-1.068), and 1.043 (95%CI:0.985-1.105), respectively. CONCLUSIONS: During the COVID-19 pandemic, community-dwelling schizophrenia patients had a low rate of regular medication adherence. This was particularly true of those who were older adults, less educated and living in rural areas. The results of this study suggest that strengthening social support may effectively improve medication adherence for those patients.

Clozapine-Induced Myocarditis in a Young Man with Refractory Schizophrenia: Case Report of a Rare Adverse Event and Review of the Literature.

BACKGROUND Myocarditis is cardiac muscle inflammation caused by infectious or noninfectious agents. Rarely, clozapine, an atypical antipsychotic drug used to treat resistant schizophrenia, has been reported to cause myocarditis, as we report in this case. CASE REPORT A 29-year-old man, who was known to have schizophrenia and was on olanzapine therapy, presented in our Emergency Department with active psychosis, and was subsequently admitted to the psychiatric ward for refractory schizophrenia. He was started on clozapine, which was cross-titrated with olanzapine. On day 20 of being treated with clozapine, he developed a high-grade fever and chest pain. EKG demonstrated new-onset prolonged QT corrected for heart rate (QTc), premature ventricular contractions, ST-T wave changes with an increased ventricular rate, and ventricular bigeminy with elevated troponin and inflammatory markers. Echocardiography showed a reduced left ventricular ejection fraction. Coronary angiography showed normal coronary arteries, low cardiac output, and cardiac index consistent with cardiogenic shock was also observed. Other pertinent laboratory results included negative respiratory viral panel, including COVID-19 PCR, negative blood cultures, and negative stool screen for ova and parasite. Clozapine was discontinued and the patient received management for heart failure with reduced ejection fraction. He improved clinically with return of EKG to normal sinus rhythm and improved left ventricular ejection fraction on repeat echocardiogram. CONCLUSIONS Acute myocarditis can occur due to a myriad of causes, both infectious and noninfectious; thus, determining the lesser-known causes, such as drug-related etiology, is essential to provide appropriate treatment for patients.

Evaluation of patient satisfaction and perceptions of a long-acting injectable antipsychotic medication administration service in a community-based pharmacy during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, restrictions, and social distancing requirements for medical offices reduced scheduling availability and increased virtual televisits by providers. COVID-19 restrictions created a barrier to health care access for patients who are being administered long-acting injectable antipsychotics (LAIs) in an already vulnerable population. OBJECTIVE: To describe an LAI medication administration service at a community-based pharmacy during the COVID-19 pandemic, to evaluate patient satisfaction with the administration of LAIs by a pharmacist service in a community-based pharmacy during the COVID-19 pandemic, and to compare the patient's perceptions of receiving LAIs in a community-based pharmacy with those in another setting previously used for medication administration. PRACTICE DESCRIPTION: Independent full-service community-based pharmacy. PRACTICE INNOVATION: Implementation of an LAI administration service after an increase in provider referrals of patients to the community-based pharmacy during the COVID-19 pandemic. EVALUATION METHODS: A 4-month prospective convenience sample study conducted to evaluate the LAI medication administration service. The survey containing 32 questions was adapted with permission from a previous survey administered in a large grocery store chain to a similar population. Survey results were reported using descriptive statistics. RESULTS: Eleven patients completed the survey. A total of 82% of patients strongly agreed that they felt comfortable with receiving this service at the community-based pharmacy and were satisfied with the privacy during the service. Seventy-one percent of patients who received this service elsewhere strongly agreed the LAI medication administration service was more convenient than a similar service received elsewhere, yet only 18% of patients strongly agreed that the community-based pharmacy was near their work or home. CONCLUSION: A medication administration service for LAIs was developed in a community-based pharmacy, and patients were satisfied with the service. Further research needs to be completed to evaluate health outcomes and financial implications of this service for the patient and health care system.

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review.

BACKGROUND: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19. AREAS OF UNCERTAINTY: In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection? DATA SOURCES: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis. THERAPEUTIC ADVANCES: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients. RESULTS: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia. CONCLUSIONS: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.

Effect of Integrated Psychobehavioral Care on Emotional-Behavioral Responses, Cognitive Changes in Outpatients with Schizophrenia Followed Up: Based on a Prospective Randomized Controlled Study.

Background: In recent years, influenced by the continuous improvement and development of the medical service model and the increasing demands of modern people for the quality of clinical care, the clinical treatment of schizophrenic groups has also received widespread attention and importance from all sectors of society. Psychobehavioral care is administered to patients during active antipsychotic treatment, which can maximize the patient's cooperation with clinical work and thus play an auxiliary role in treatment. Aims: To investigate the impact of emotional-behavioral responses, cognitive changes in outpatient follow-up of schizophrenic patients with integrated psychobehavioral care. Materials and Methods: One hundred cases of schizophrenia patients with outpatient follow-up in our hospital from March 2017 to March 2019 were selected as prospective study subjects and divided into a comparison group and an observation group of 50 cases each according to a random number table. Among them, the comparison group implemented conventional psychobehavioral care, and the observation group implemented integrated psychobehavioral care. The differences in compliance behavior, negative emotions, cognitive behavioral changes, and pain scores before and after care of schizophrenia patients in the outpatient follow-up were compared between the two groups. Results: After care, the compliance behavior, negative emotions, cognitive behavioral changes, and pain scores of schizophrenia patients in both groups with outpatient follow-up were significantly improved and significantly higher in the observation group than in the comparison group, and statistics showed that this difference was statistically significant (P < 0.05). Conclusion: Integrated psychobehavioral care combined with conventional psychobehavioral care can effectively enhance the compliance behavior of outpatient follow-up schizophrenia patients, improve the negative emotions and pain of patients, and facilitate the active treatment of patients to improve their prognosis. It has some reference value for outpatient follow-up schizophrenia patient care.

Study protocol for the development and internal validation of Schizophrenia Prediction of Resistance to Treatment (SPIRIT): a clinical tool for predicting risk of treatment resistance to antipsychotics in first-episode schizophrenia.

INTRODUCTION: Treatment-resistant schizophrenia (TRS) is associated with significant impairment of functioning and high treatment costs. Identification of patients at high risk of TRS at the time of their initial diagnosis may significantly improve clinical outcomes and minimise social and functional disability. We aim to develop a prognostic model for predicting the risk of developing TRS in patients with first-episode schizophrenia and to examine its potential utility and acceptability as a clinical decision tool. METHODS AND ANALYSIS: We will use two well-characterised longitudinal UK-based first-episode psychosis cohorts: Aetiology and Ethnicity in Schizophrenia and Other Psychoses and Genetics and Psychosis for which data have been collected on sociodemographic and clinical characteristics. We will identify candidate predictors for the model based on current literature and stakeholder consultation. Model development will use all data, with the number of candidate predictors restricted according to available sample size and event rate. A model for predicting risk of TRS will be developed based on penalised regression, with missing data handled using multiple imputation. Internal validation will be undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. The clinical utility of the model in terms of clinically relevant risk thresholds will be evaluated using net benefit and decision curves (comparative to competing strategies). Consultation with patients and clinical stakeholders will determine potential thresholds of risk for treatment decision-making. The acceptability of embedding the model as a clinical tool will be explored using qualitative focus groups with up to 20 clinicians in total from early intervention services. Clinicians will be recruited from services in Stafford and London with the focus groups being held via an online platform. ETHICS AND DISSEMINATION: The development of the prognostic model will be based on anonymised data from existing cohorts, for which ethical approval is in place. Ethical approval has been obtained from Keele University for the qualitative focus groups within early intervention in psychosis services (ref: MH-210174). Suitable processes are in place to obtain informed consent for National Health Service staff taking part in interviews or focus groups. A study information sheet with cover letter and consent form have been prepared and approved by the local Research Ethics Committee. Findings will be shared through peer-reviewed publications, conference presentations and social media. A lay summary will be published on collaborator websites.