Clinical Characterization, Course, and Treatment of Othello Syndrome: A Case Series and Systematic Review of the Literature.

BACKGROUND: Othello syndrome (OS) is a condition characterized by a delusion of jealousy that one's spouse is having extramarital affairs. As in the eponymous Shakespearean tragedy, there is an unfortunate risk of violence. For patients with these symptoms, consultation-liaison psychiatrists may be asked to assist with evaluating the differential diagnosis, assessing safety, and developing treatment options. OBJECTIVE: This study's objective was to solidify current knowledge of the clinical presentations and management of OS through a systematic review of the literature and description of 2 new cases. METHODS: We conducted a literature search from the start of relevant databases through August 2023 to identify English language case reports of adults (≥18 years) with OS that described clinical evaluations, biological treatments, and outcomes. We extracted demographics, proposed etiologies, treatment choices and responses, duration of delusions, comorbid psychiatric symptoms, neuro-radiographic findings, and presence of physical violence. We reported clinical findings for 2 new cases. RESULTS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we screened 705 abstracts and conducted full-text reviews of 118 articles to identify 73 cases published from 1983 to 2023 meeting inclusion criteria. The mean age was 58.2 years with male predominance (M:F = 1.88). Etiologies included primary psychiatric disorders (16, 22%), other medical conditions (38, 52%), and medications or other substances (19, 26%). Delusional disorder, cerebrovascular accident, and dopaminergic agonists were the most common etiologies, respectively, in these groups. Antipsychotics were the most common treatment (57, 78%). Symptom remission was reported in 51 (70%) cases. The average duration of OS was 39.5 months. Of 32 cases reporting brain imaging insults, 12 of 20 (60%) showed right-sided lesions, and 8 of 20 (40%) showed left-sided lesions, with 9 of 32 (28%) located in the frontal lobes. The most commonly co-existing psychiatric symptom was depression (14, 19%). Violence was reported in 25 cases (34%). Our 2 new cases were consistent with these findings. CONCLUSIONS: OS may be a manifestation of several neuropsychiatric conditions, primarily delusional disorder, cerebrovascular accident, Alzheimer's dementia, and the use of dopaminergic agonists. One-third of cases include violent behaviors. It appears to respond to antipsychotic medications, but treatment is delayed more than 3 years on average. Available data have not localized OS to a specific brain region.

CLINICAL AND GENETIC FEATURES OF PERSONALIZED ANTIPSYCHOTIC THERAPY OF PATIENTS WITH PARANOID SCHIZOPHRENIA OF THE KAZAKH ETHNIC GROUP IN THE REPUBLIC OF KAZAKHSTAN.

The problems of schizophrenia therapy occupy a leading place in both foreign and domestic clinical psychiatry. The paper presents the results of a study to identify reliable biomarkers for predicting antipsychotic therapy of patients with paranoid schizophrenia of the Kazakh ethnic group in the Republic of Kazakhstan, conducted within the framework of the project: "National program for the introduction of personalized and preventive medicine in the Republic of Kazakhstan" IRN ОР12165486. The effectiveness and tolerability of antipsychotic drugs used in the treatment of paranoid schizophrenia in the Republic of Kazakhstan according to clinical treatment protocols are analyzed. Gender and age-specific dynamics in the clinic of paranoid schizophrenia in antipsychotic therapy in persons of Kazakh ethnicity are described. Certain genetic features of representatives of the Kazakh ethnic group have been identified, which can influence the effectiveness and tolerability of antipsychotic drugs, which determines the basis of an innovative approach to personalized therapy of paranoid schizophrenia in patients of the Kazakh ethnic group in the Republic of Kazakhstan.

Hepatoxicity induced by clozapine: Case report and brief review.

INTRODUCTION: Antipsychotics are drugs that can produce transient elevations of hepatic enzymes. Clozapine is an atypical antipsychotic used in treatment-resistant schizophrenia and there is evidence that it can produce elevations of hepatic transaminases, expression of liver damage in a hepatocellular pattern. METHODS: Case report and non-systematic review of the relevant literature. CASE PRESENTATION: A 39-year-old woman with a diagnosis of paranoid schizophrenia attended the emergency department of a general hospital for nausea, vomiting and jaundice that appeared after the initiation of clozapine. There was no clinical improvement during hospitalisation, and death occurred after 44 days. LITERATURE REVIEW: Clozapine can increase the liver enzyme levels transiently and asymptomatically; however, there are clinical criteria that recommend the withdrawal of the antipsychotic. CONCLUSIONS: This is the third case reported in the literature of a fatal outcome of clozapine-induced hepatotoxicity.

[An effect of antipsychotic and anticholinergic treatment on cognitive function in patients with schizophrenia]. / Vliyanie antipsikhoticheskoi i antikholinergicheskoi terapii na kognitivnye funktsii u bol'nykh shizofreniei.

OBJECTIVE: To reveal the relationships between antipsychotic and anticholinergic drugs and cognitive functions in patients with schizophrenia. MATERIAL AND METHODS: The observational prospective study was conducted at the Bekhterev National Medical Center of Psychiatry and Neurology. The study involved 41 patients (22 men and 19 women) with paranoid schizophrenia, according to ICD 10 criteria, aged 30.12±8.24 years on stable antipsychotic monotherapy or in combination with anticholinergic drug (trihexiphenidyl). Cognitive functions were assessed using the «Brief Assessment of Cognitive Function in Patients with Schizophrenia¼ (BACS) scale, severity of mental state and extrapyramidal disturbances were measured using the «Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale for Assessment of Extrapyramidal Side Effects (SAS). All examination procedures were performed twice at weeks 2 and 8 of therapy. Patients were divided into 2 groups according to the type of antipsychotic therapy. Twelve patients received first generation antipsychotics (FGAs) (group 1), 29 patients received second generation antipsychotics (SGAs) (group 2). RESULTS: Patients receiving SGAs had a significant decrease in the overall SAS score at week 8 of therapy compared with data at week 2, and there was an improvement in cognitive function, unlike patients receiving FGAs. There were also changes on BACS tests the digit sequencing (V=51.5, p=0.007), token motor task (V=75.5, p=0.007) and Tower of London (V=52, p=0.027) only in patients of group 2. CONCLUSION: The improved tolerance to the drug, as well as cognitive measures, was shown in patients taking SGAs by week 8. Our study confirms the importance of adhering to the minimum effective dose of antipsychotic drugs for the treatment of schizophrenia to prevent cognitive impairment, and to give preference to SGAs in the choice of treatment.

Uso de antipsicóticos atípicos no tratamento da esquizofrenia no Sistema Único de Saúde do Brasil: estudo de coorte, 2008-2017 / Uso de antipsicóticos atípicos en el tratamiento de la esquizofrenia en el Sistema Único de Salud de Brasil: estudio de 2008 a 2017 / Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017

Objective: to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. Methods: this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. Results: of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. Conclusion: the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

Objetivo: investigar las características sociodemográficas y clínicas de los usuarios de antipsicóticos atípicos, atendidos por el Componente Especializado de Asistencia Farmacéutica (CEAF) para el tratamiento de la esquizofrenia en Brasil, de 2008 a 2017. Métodos: estudio de cohorte retrospectivo utilizando registros de autorizaciones de trámites de alta complejidad del Sistema de Información Ambulatorio del SUS, de todos los estados brasileños. Resultados: de los 759.654 usuários identificados, el 50,5% era del sexo feminino de la región Sudeste (60,2%), diagnosticadas con esquizofrenia paranoide (77,6%). Hubo una mayor prevalencia de risperidona (63,3%) entre niños y adolescentes; de olanzapina (34,0%) en adultos; y quetiapina (47,4%) en ancianos. Alrededor del 40% de los niños/adolescentes estaba bajo uso no autorizado de antipsicóticos según la edad. La adherencia al CEAF fue alta (82%), y la deserción a los seis meses fue del 24%. Conclusión: los hallazgos amplían el conocimiento sobre el perfil sociodemográfico y clínico de los usuarios y destacan la práctica del uso off-label.

Objetivo: investigar características sociodemográficas e clínicas de usuários de antipsicóticos atípicos assistidos pelo Componente Especializado da Assistência Farmacêutica (CEAF), para tratamento da esquizofrenia no Brasil, de 2008 a 2017. Métodos: estudo de coorte retrospectivo utilizando registros das autorizações de procedimentos de alta complexidade do Sistema de Informações Ambulatoriais do Sistema Único de Saúde, de todos os estados brasileiros. Resultados: dos 759.654 usuários, 50,5% eram do sexo feminino, da região Sudeste (60,2%), diagnosticados com esquizofrenia paranoide (77,6%); observou-se maior prevalência de uso da risperidona (63,3%) entre crianças/adolescentes; de olanzapina (34,0%), em adultos; e quetiapina (47,4%), nos idosos; cerca de 40% das crianças/ adolescentes estavam sob uso off-label de antipsicóticos segundo a idade; a adesão ao CEAF foi alta (82%), e o abandono em seis meses foi de 24%. Conclusão: os achados ampliam o conhecimento sobre perfil sociodemográfico e clínico dos usuários e destacam a prática do uso off-label.

Long-acting injectable paliperidone palmitate induced severe cutaneous allergic reaction in a patient with first episode delusional disorder tolerating oral paliperidone regimen: a case report.

BACKGROUND: Paliperidone is a second-generation antipsychotic agent that is effective in the treatment of schizophrenia and schizoaffective disorder as well as an adjunct to mood stabilizers and antidepressants for bipolar and depressive disorders. Paliperidone is available in both oral and injection forms. Here we report an unexpected case of cutaneous allergic reaction induced by paliperidone long-acting injection (LAI) following oral tolerance. CASE PRESENTATION: A 55-year-old man with first episode delusional disorder was treated with paliperidone tablets with tolerance. On day seven he received the paliperidone LAI and developed an allergic reaction in minutes including flushing of the face, widespread urticaria with mild airway constriction. The allergic symptoms were relived following the administration of antihistamine within several minutes. CONCLUSION: The allergic reaction that occurred post administration of the paliperidone LAI but not the oral tablets suggest it is likely due to the excipients in the formulation of the LAI rather than paliperidone itself. This case highlights the necessity of monitoring allergic reactions in psychiatric patients when converting from oral to LAI format of paliperidone.

[Second-generation long-acting injectable antipsychotics in clinical practice]. / In"ektsionnye antipsikhotiki-prolongi vtoroi generatsii v klinicheskoi praktike.

On the example of 5 clinical cases of paranoid schizophrenia at different stages of the development of the disease, the therapeutic tactics of using drugs from the group of second-generation injectable prolong antipsychotics to solve problems that arise during anti-relapse therapy are shown. The research data substantiating these approaches are presented. Various combination therapy options are discussed, including at the stage of drug replacement and the appointment of a second-generation long-acting injectable antipsychotic.

Factors Influencing Adherence to Antipsychotic Medications in Women with Delusional Disorder: A Narrative Review.

BACKGROUND: Adherence to medication regimens is of great importance in psychiatry because drugs sometimes need to be taken for long durations in order to maintain health and function. OBJECTIVE: This study aimed to review influences on adherence to antipsychotic medications, the treatment of choice for the delusional disorder (DD), and to focus on adherence in women with DD. METHODS: This is a non-systematic narrative review of papers published since 2000 using PubMed and Google Scholar, focusing on women with DD and medication adherence. RESULTS: Several factors have been identified as exerting influence on adherence in women with persistent delusional symptoms who are treated with antipsychotics. Personality features, intensity of delusion, perception of adverse effects, and cognitive impairment are patient factors. Clinical time spent with the patient, clarity of communication, and regular drug monitoring are responsibilities of the health provider. Factors that neither patient nor clinician can control are the social determinants of health, such as poverty, easy access to healthcare, and cultural variables. CONCLUSION: There has been little investigation of factors that influence adherence in the target population, e.g., women with DD. Preliminary results of this literature search indicate that solutions from outside the field of DD may apply to this population. Overall, a solid therapeutic alliance appears to be the best hedge against nonadherence.

Clozapine induced pericarditis: A case report.

Clozapine is a second-generation antipsychotic often used for treatment-refractory schizophrenia and has many adverse effects. Cardiac adverse events potentiated by clozapine include myocarditis which is a black box warning. Even more rarely, there are multiple cases of pericarditis reported in the literature. This is a case report of a 32-year old male with paranoid schizophrenia who developed pericarditis after initiation and titration of clozapine in the inpatient psychiatry unit. Patient presented with chest pain, persistent tachycardia, and orthostatic hypotension two weeks after titration of clozapine. The diagnosis of pericarditis was supported by the repeat electrocardiogram which revealed PR depressions, the audible friction rub, and the pleuritic/episodic nature of the chest pain. All other possible causes of pericarditis were ruled out and clozapine was suspected as the most likely explanation. The pericarditis resolved with treatment of colchine and ibuprofen on evidence from a repeat echocardiogram. This case report demonstrates and supports few cases of clozapine induced pericarditis in the literature. Cardiac events of clozapine can be life-threatening; therefore, greater baseline and subsequent cardiac monitoring may be implicated in the future.

[An effect of cholinesterase blockade on negative symptoms in schizophrenia]. / Vliyanie blokady kholinesterazy na negativnye rasstroistva pri shizofrenii.

Abstruct. OBJECTIVE: To assess the possibilities of influencing the severity of negative disorders in schizophrenic patients with cholinesterase blockade. MATERIAL AND METHODS: The study included stable 26 patients (13 of them women), average age 40.4 (SD 11.7) with paranoid schizophrenia, episodic form according to ICD-10). All patients received antipsychotic therapy, which was not changed at least for 2 months. We used psychometric scales (Positive and Negative Syndrome Assessment Scale (PANSS), Global Functioning Scale (GAF), neurocognitive techniques (Brief Assessment of Cognition in Schizophrenia-BACS), projective psychological techniques (Rorschach test). RESULTS AND CONCLUSION: The results of the study showed that augmentation of maintenance antipsychotic therapy with a cholinesterase blocker (ipidacrine at a dose of 20 mg per day) had positive impact on negative symptoms, decreasing the severity of emotional deficiency. The positive changes of cognitive impairment, measured with BACS, occurred regardless of changes in the severity of negative disorders, measured with PANSS. The Rorschach test showed an improvement in the conventional orientation of the patients' thinking. No exacerbation of psychotic symptoms was registered.

Deep vein thrombosis on the fourth day of risperidone therapy.

Deep vein thrombosis has been recognised as a complication of antipsychotic treatment and is reported to be more common with atypical antipsychotics. Risperidone is a second-generation atypical antipsychotic and there have been case reports of risperidone-associated deep vein thrombosis, most of them reporting the complication from 2 weeks to a few months of initiation of therapy. Here, we are reporting a case of deep vein thrombosis in a male patient in his early forties with paranoid schizophrenia, which presented on the fourth day of starting risperidone therapy. This case is being reported to highlight the fact that deep vein thrombosis can occur as early as fourth day of initiation of risperidone therapy, that too at a low dose (2 mg/day). The case also emphasises the importance of monitoring these patients for this rare but potentially serious adverse effect from the first day itself after initiation of a new antipsychotic.

Effectiveness of pharmacotherapies for delusional disorder in a Swedish national cohort of 9076 patients.

BACKGROUND: Little is known on the effective pharmacological treatment of delusional disorder. AIMS: Study the comparative effectiveness of pharmacotherapies in the prevention of hospitalization due to psychosis and work disability in delusional disorder. METHODS: Observational registry based cohort study including everyone in Sweden diagnosed with delusional disorder (N = 9076;mean follow-up time 4.9 years). The primary analysis was Cox Proportional Hazards within-individual analysis. Results are reported as adjusted hazard ratios (HRs). RESULTS: Among the cohort (4835 males/4241 females;mean [SD] age 44.1 [12.5] years), 2074 persons had at least one hospitalization due to psychosis. Risk for hospitalization due to psychosis was 46% lower when any antipsychotic was used (HR 0.54, 95%CI 0.38-0.77, p < 0.001). Use of clozapine (HR 0.24, 95%CI 0.07-0.77, p = 0.016), any long-acting injectable (LAI; HR 0.28, 95%CI 0.16-0.49, p < 0.0001) and oral olanzapine (HR 0.36, 95%CI 0.20-0.67, p = 0.001) were associated with lowest risk. Among those not on disability pension at start of follow-up (n = 5025), in comparison to no use of antipsychotics, use of clozapine (HR 0.08, 95%CI 0.01-0.52, p = 0.008), any LAI (HR 0.44, 95%CI 0.25-0.79, p = 0.006) and oral aripiprazole (HR 0.52, 95%CI 0.31-0.85, p = 0.009) were associated with lowest risk of work disability. CONCLUSIONS: Use of antipsychotics was associated with a reduced risk of hospitalization due to psychosis and work disability in delusional disorder, with use of clozapine and long-acting injectables being associated with the lowest risk for these very relevant end-points for both individual suffering and costs to society. Clinical trials with these treatments are urgently needed to make informed clinical treatment recommendations.

A genome-wide association study identifies a gene network associated with paranoid schizophrenia and antipsychotics-induced tardive dyskinesia.

In the present study we conducted a genome-wide association study (GWAS) in a cohort of 505 patients with paranoid schizophrenia (SCZ), of which 95 had tardive dyskinesia (TD), and 503 healthy controls. Using data generated by the PsychENCODE Consortium (PEC) and other bioinformatic databases, we revealed a gene network, implicated in neurodevelopment and brain function, associated with both these disorders. Almost all these genes are in gene or isoform co-expression PEC network modules important for the functioning of the brain; the activity of these networks is also altered in SCZ, bipolar disorder and autism spectrum disorders. The associated PEC network modules are enriched for gene ontology terms relevant to the brain development and function (CNS development, neuron development, axon ensheathment, synapse, synaptic vesicle cycle, and signaling receptor activity) and to the immune system (inflammatory response). Results of the present study suggest that orofacial and limbtruncal types of TD seem to share the molecular network with SCZ. Paranoid SCZ and abnormal involuntary movements that indicate the orofacial type of TD are associated with the same genomic loci on chromosomes 3p22.2, 8q21.13, and 13q14.2. The limbtruncal type of TD is associated with a locus on chromosome 3p13 where the best functional candidate is FOXP1, a high-confidence SCZ gene. The results of this study shed light on common pathogenic mechanisms for SCZ and TD, and indicate that the pathogenesis of the orofacial and limbtruncal types of TD might be driven by interacting genes implicated in neurodevelopment.

[Psychosis Associated with Herbal Products: Iatrogenic Delusional Disorder]. / Psicose Associada a Produtos de Ervanária: Perturbação Delirante Orgânica de Carácter Iatrogénico.

Metabolic, toxic or structural brain changes may present as psychotic symptoms. Organic delusional disorders are characterized by the presence of delusional ideas with evidence of brain dysfunction. Iatrogenesis may be a cause of this dysfunction. We present a case of neuropsychiatric symptoms, including delusional disorder, secondary to the use of herbal products. The patient's perception regarding the safety of natural products might result in an omission to report their use during clinical history taking, and thus its use should be actively questioned.

Sintomas psicóticos podem constituir a forma de apresentação de alterações estruturais, metabólicas ou tóxicas. As perturbações delirantes orgânicas são caraterizadas pela presença de ideias delirantes com evidência de disfunção cerebral. A iatrogenia pode ser uma causa desta disfunção. Apresentamos um caso de sintomas neuropsiquiátricos, incluindo perturbação delirante, secundária ao uso de produtos de ervanária. A noção de inocuidade associada a estes produtos origina que o consumo dos mesmos não seja referido espontaneamente pelo doente na recolha da história clínica, pelo que a sua utilização deve ser ativamente questionada.

Association of the genetic polymorphisms of metabolizing enzymes, transporters, target receptors and their interactions with treatment response to olanzapine in chinese han schizophrenia patients.

Olanzapine is an atypical antipsychotic drug that has been increasingly used for treatment in schizophrenia. It has been observed that olanzapine responses in schizophrenia patients vary individually, but the reason has not been elucidated. In the study, we aimed to comprehensively explore the relationships between olanzapine responses and genetic polymorphisms of drug metabolizing enzymes, transporters and target receptors, and so as to interpret the reason of good and poor responses of olanzapine. A total of 241 Chinese Han paranoid schizophrenia who treated with olanzapine alone for 4 weeks were recruited. The positive and negative symptom scale (PANSS) was used to evaluate the efficacy of olanzapine. The genetic polymorphisms were detected by improved multiple ligase detection reaction (iMLDR). Multivariate logistic regression analysis suggested that the genetic polymorphisms of CYP1A2 rs762551, UGT1A4 rs2011425, ABCB1 rs1045642, DRD2 rs1799732 and rs1799978, 5-HTR2A rs6311 were significantly associated with olanzapine response. Multifactor dimensionality reduction (MDR) analysis showed that there was a negative interaction between CYP1A2 rs762551, ABCB1 rs1045642, DRD2 rs1799978, 5-HTR2A rs6311 and the interaction model was the optimal model. Our findings could partially explain the different olanzapine outcome and provided evidence for clarifying the predictive indicators of olanzapine response in further.