Clozapine prescription trends in Brazil in the last decade

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

Schneider's first-rank symptoms as predictors of remission in antipsychotic-naive first-episode psychosis

Objective: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis. Methods: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS. Results: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one's actions, and thought broadcasting. Conclusion: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider's classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

Hair cortisol in drug-naïve first-episode individuals with psychosis

Objectives: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. Methods: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Results: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.

Clinical characteristics and influence of childhood trauma on the prodrome of bipolar disorder

Objectives: To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms. Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ). Results: Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8±68.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6±23.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia. Conclusions: This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.

Determinants of adherence to treatment in first-episode psychosis: a comprehensive review

Objective: To conduct a comprehensive review of current evidence on factors for nonadherence to treatment in individuals with first-episode psychosis (FEP). Methods: MEDLINE, LILACS, PsycINFO, and SciELO databases were searched with the keywords first episode psychosis, factor, adherence, nonadherence, engagement, disengagement, compliance, and intervention. References of selected studies were consulted for relevant articles. Results: A total of 157 articles were screened, of which 33 articles were retained for full review. The factors related to nonadherence were: a) patient-related (e.g., lower education level, persistent substance use, forensic history, unemployment, history of physical abuse); b) environment-related (e.g., no family involved in treatment, social adjustment difficulties); c) medication-related (e.g., rapid remission of negative symptoms when starting treatment, therapeutic alliance); and d) illness-related (e.g., more positive symptoms, more relapses). Treatment factors that improve adherence include a good therapeutic alliance and a voluntary first admission when hospitalization occurs. Conclusion: The results of this review suggest that nonadherence to treatment in FEP is multifactorial. Many of these factors are modifiable and can be specifically targeted in early intervention programs. Very few studies have assessed strategies to raise adherence in FEP. .

Factor structure of the Positive and Negative Syndrome Scale (PANSS) in Brazil: convergent validation of the Brazilian version

Objectives: The Positive and Negative Syndrome Scale (PANSS) was developed to assess the symptoms of schizophrenia dimensionally. Although it is widely used in clinical trials in Brazil, it is not fully validated. The aim of this study is to assess the factor structure of the Brazilian PANSS and generate validation data for its current version. Methods: A total of 292 patients diagnosed with schizophrenia were enrolled. Results: Principal component analysis suggested a forced five-factor final model that accounted for 58.44% of the total variance, composed of negative, disorganization/cognition, excitement, positive, and depression/anxiety. Conclusion: The Brazilian PANSS has a similar factor structure and internal consistency compared to its other country versions.

Translation and adaptation of the Bipolar Prodrome Symptom Scale-Retrospective: Patient Version to Brazilian portuguese / Tradução e adaptação da Bipolar Prodrome Symptom Scale-Retrospective: Patient Version para português brasileiro

BACKGROUND: Bipolar disorder (BD) is a chronic and often severe mental disease, associated with a significant burden in affected individuals. The characterization of a premorbid (prodromal) period and possible development of preventive interventions are recent advances in this field. Attempts to characterize high-risk stages in BD, identifying symptoms prior to the emergence of a first manic/hypomanic episode, have been limited by a lack of standardized criteria and instruments for assessment. The Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), developed by Correll and collaborators, retrospectively evaluates symptoms that occur prior to a first full mood episode in individuals with BD. OBJECTIVE: To describe the translation and adaptation process of the BPSS-R to Brazilian Portuguese. METHOD: Translation was conducted as follows: 1) translation of the scale from English to Brazilian Portuguese by authors who have Portuguese as their first language; 2) merging of the two versions by a committee of specialists; 3) back-translation to English by a translator who is an English native speaker; 4) correction of the new version in English by the author of the original scale; 5) finalization of the new version in Brazilian Portuguese. RESULTS: All the steps of the translation process were successfully accomplished, resulting in a final version of the instrument. CONCLUSIONS: The Brazilian Portuguese version of the BPSS-R is a potentially useful instrument to investigate prodromal period of BD in Brazil

INTRODUÇÃO: O transtorno bipolar (TB) é um transtorno mental crônico e muitas vezes grave, associado a um significativo prejuízo psicossocial nos indivíduos afetados. A caracterização de um período pré-mórbido (prodrômico) e o possível desenvolvimento de intervenções preventivas são avanços recentes na área. Tentativas de caracterizar estágios de alto risco para o TB, através da identificação de sintomas antes do aparecimento de um primeiro episódio maníaco/hipomaníaco, têm sido limitadas pela falta de critérios padronizados e instrumentos de avaliação. A Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), desenvolvida por Correll e colaboradores, avalia retrospectivamente os sintomas que ocorrem antes de um episódio sindrômico de humor em indivíduos com TB. OBJETIVO: Descrever o processo de tradução e adaptação da BPSS-R para português brasileiro. MÉTODO: A tradução foi conduzida como segue: 1) tradução da escala de inglês para português brasileiro por autores que têm o português como língua materna; 2) junção das duas versões por um comitê de especialistas; 3) retrotradução para inglês por um tradutor que tem inglês como língua materna; 4) correção da nova versão em inglês pelo autor do instrumento original; 5) finalização da nova versão em português brasileiro. RESULTADOS: Todos os passos do processo de tradução foram completados com sucesso, resultando em uma versão final do instrumento. CONCLUSÕES: A versão da BPSS-R em português brasileiro é um instrumento potencialmente útil para investigar o período prodrômico do TB no Brasil