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1.
Brain Sci ; 13(8)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37626562

RESUMO

(1) Background: The treatment of substance addiction is challenging and has persisted for decades, with only a few therapeutic options. Although there are some recommendations for specific treatments for Alcohol Use Disorder (AUD), there is no specific medication used to treat alcohol cravings, which could benefit millions of patients that are suffering from alcoholism. Cravings, or the urge to use drugs, refer to the desire to experience the effects of a previously experienced psychoactive substance. (2) Methods: We included original studies of alcohol abuse or dependence extracted from a controlled, blind, pharmacological treatment study which presented measures and outcomes related to alcohol cravings. (3) Results: Specific drugs used for the treatment of alcoholism, such as Naltrexone and Acamprosate, have had the best results in relieving craving symptoms, as well as promoting abstinence. Baclofen and anticonvulsants such as Gabapentin and Topiramate have shown good results in promoting abstinence and the cessation of cravings. (4) Conclusions: Specific drugs used for the treatment of alcoholism to obtain the best results can be considered the gold standard for promoting abstinence and relieving cravings. Anticonvulsants and Baclofen also had good results, with these medications being considered as second-line ones. Varenicline is an option for alcohol dependents who also concomitantly ingest tobacco.

2.
Brain Sci ; 13(7)2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37508922

RESUMO

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as 'K2', 'K9' or 'Spice'. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings.

3.
Rev Paul Pediatr ; 41: e2021344, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36921167

RESUMO

OBJECTIVE: This study aimed to analyze the effect of major depressive disorder (MDD) as a risk factor for suicidal ideation in individuals whose ages varied from 11 to 24 years and who were attending educational institutions. DATA SOURCE: A systematic review was carried out by searching in PubMed and Biblioteca Virtual em Saúde (BVS). Original studies conducted in educational institutions, including individuals whose age varied from 11 to 24 years, in English, Spanish, or Portuguese were included. DATA SYNTHESIS: Eight studies were selected for the meta-analysis, including 35,443 youths, with an average age of 16.8 years, predominantly female (51.2%), and from middle-income Asian countries (91.6%). An odds ratio of MDD of 3.89 (95%CI 2.46-6.17) for suicide ideation in youth was found. Subgroup analysis showed higher effects in Asia (OR=4.71; 95%CI 3.22-6.89) than Americas (OR=1.71; 95%CI 1.44-2.03). The meta-regression model indicated that younger adolescents (coef=-0.63; 95%CI 1.09--0.18; p<0.01) and older studies (coef=-0.23; 95%CI 0.039--0.08; p<0.01) presented higher effects of MDD on suicidal ideation. CONCLUSIONS: Early detection and treatment of MDD in youth patients are of utmost importance for preventing suicidal ideation. Educational institutions could play an important role in the early detection and intervention.


Assuntos
Transtorno Depressivo Maior , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Transtorno Depressivo Maior/epidemiologia , Razão de Chances , Fatores de Risco , Instituições Acadêmicas , Ideação Suicida
4.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 41: e2021344, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1422832

RESUMO

Abstract Objective: This study aimed to analyze the effect of major depressive disorder (MDD) as a risk factor for suicidal ideation in individuals whose ages varied from 11 to 24 years and who were attending educational institutions. Data source: A systematic review was carried out by searching in PubMed and Biblioteca Virtual em Saúde (BVS). Original studies conducted in educational institutions, including individuals whose age varied from 11 to 24 years, in English, Spanish, or Portuguese were included. Data synthesis: Eight studies were selected for the meta-analysis, including 35,443 youths, with an average age of 16.8 years, predominantly female (51.2%), and from middle-income Asian countries (91.6%). An odds ratio of MDD of 3.89 (95%CI 2.46-6.17) for suicide ideation in youth was found. Subgroup analysis showed higher effects in Asia (OR=4.71; 95%CI 3.22-6.89) than Americas (OR=1.71; 95%CI 1.44-2.03). The meta-regression model indicated that younger adolescents (coef=-0.63; 95%CI 1.09--0.18; p<0.01) and older studies (coef=-0.23; 95%CI 0.039--0.08; p<0.01) presented higher effects of MDD on suicidal ideation. Conclusions: Early detection and treatment of MDD in youth patients are of utmost importance for preventing suicidal ideation. Educational institutions could play an important role in the early detection and intervention.


Resumo Objetivo: Analisar o efeito do transtorno depressivo maior (TDM) como fator de risco para a ideação suicida em indivíduos com idades entre 11 e 24 anos que frequentam instituições de ensino. Fontes de dados: Revisão sistemática realizada até agosto de 2020 por meio de buscas nas bases United States National Library of Medicine (PubMed) e Biblioteca Virtual em Saúde (BVS), sem limitações quanto à data de publicação. Síntese dos dados: Oito estudos foram selecionados para a metanálise, incluindo 35.443 jovens com idade média de 16,8 anos, predominantemente do sexo feminino (51,2%) e de países asiáticos de renda média (91,6%). Foi encontrado odds ratio (OR) de TDM de 3,89 (intervalo de confiança — IC95% 2,46-6,17) para a ideação suicida em jovens. A análise de subgrupo mostrou efeitos maiores na Ásia (OR=4,71; IC95% 3,22-6,89) do que nas Américas (OR=1,71; IC95% 1,44-2,03). O modelo de metarregressão demonstrou que adolescentes mais jovens (coef=-0,63; IC95% -1,09--0,18; p<0,01) e estudos mais antigos (coef=-0,23; IC95% -0,039--0,08; p<0,01) apresentaram maiores efeitos do TDM sobre a ideação suicida. Conclusões: Observou-se relação entre TDM e ideação suicida no continente asiático, entre adolescentes mais jovens e em estudos mais antigos.

5.
São Paulo med. j ; 140(6): 781-786, Nov.-Dec. 2022. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1410228

RESUMO

ABSTRACT BACKGROUDS: Child and Adolescent Psychosocial Care Centers (Centros de Atenção Psicossocial, CAPSI) are dedicated centers for persistent psychiatric disorders, which provide an individualized therapeutic approach based on extra-hospital services. OBJECTIVES: We aimed to describe the clinico-epidemiological profiles of the patients seeking interventions at the CAPSIs. DESIGN AND SETTING: A cross-sectional study was conducted in two CAPSI in São Bernardo do Campo, SP, Brazil. One CAPSI is dedicated to the treatment of alcohol- and drug-related disorders, and the other to the treatment of other mental disorders. METHODS: In July 2017, we reviewed all active medical records of these two CAPSI, and collected the patients information including sex, race, education, type of referral, initial complaints, psychiatric diagnoses, and medication utilization. RESULTS: Of the 233 patients, 69.5% were male and 42.5% lived with their immediate family. Most of the patients were referred from other health services. Complaints on admission included agitation and aggressive behavior (30.9%). Autism spectrum disorder (ASD) was the most prevalent diagnosis (46.8%), followed by depressive disorder (13.8%). Of the patients, 81.5% were on regular medical follow-up and 70.3% were on a single medication only. CONCLUSION: Aggression complaints are the most prevalent in CAPSI, and diagnoses of ASD and psychotic disorders are more common. This situation differs from most CAPSI that present school complaints as the most prevalent, in which diagnoses of attention-deficit/hyperactivity disorder and conduct disorders are likely to be more frequent. The epidemiological profile of each CAPSI should guide the implementation of human and structural resources targeting the most prevalent complaints and diagnoses.

6.
Sao Paulo Med J ; 140(6): 781-786, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35920532

RESUMO

BACKGROUDS: Child and Adolescent Psychosocial Care Centers (Centros de Atenção Psicossocial, CAPSI) are dedicated centers for persistent psychiatric disorders, which provide an individualized therapeutic approach based on extra-hospital services. OBJECTIVES: We aimed to describe the clinico-epidemiological profiles of the patients seeking interventions at the CAPSIs. DESIGN AND SETTING: A cross-sectional study was conducted in two CAPSI in São Bernardo do Campo, SP, Brazil. One CAPSI is dedicated to the treatment of alcohol- and drug-related disorders, and the other to the treatment of other mental disorders. METHODS: In July 2017, we reviewed all active medical records of these two CAPSI, and collected the patients information including sex, race, education, type of referral, initial complaints, psychiatric diagnoses, and medication utilization. RESULTS: Of the 233 patients, 69.5% were male and 42.5% lived with their immediate family. Most of the patients were referred from other health services. Complaints on admission included agitation and aggressive behavior (30.9%). Autism spectrum disorder (ASD) was the most prevalent diagnosis (46.8%), followed by depressive disorder (13.8%). Of the patients, 81.5% were on regular medical follow-up and 70.3% were on a single medication only. CONCLUSION: Aggression complaints are the most prevalent in CAPSI, and diagnoses of ASD and psychotic disorders are more common. This situation differs from most CAPSI that present school complaints as the most prevalent, in which diagnoses of attention-deficit/hyperactivity disorder and conduct disorders are likely to be more frequent. The epidemiological profile of each CAPSI should guide the implementation of human and structural resources targeting the most prevalent complaints and diagnoses.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Reabilitação Psiquiátrica , Criança , Adolescente , Humanos , Masculino , Feminino , Estudos Transversais , Transtorno do Espectro Autista/terapia , Brasil/epidemiologia
7.
Rev Assoc Med Bras (1992) ; 68(5): 622-626, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35584485

RESUMO

OBJECTIVES: This study aimed to identify the infrastructure (e.g., availability, resources, and staff), basic metrics, and problems (e.g., network, overcrowding, resources, and infrastructure) of the psychiatric emergency services in Brazil. METHODS: This is a cross-sectional study assessing psychiatric services (n=29) listed by the Brazilian Psychiatric Association in 2019. RESULTS: Almost all the units reported 24 h/7-day availability having psychiatrists, nurses, and social workers, with 8.8 (SE=2.2) and 2.8 (SE=0.3) consultations and hospitalizations per day, respectively. Separated room for contention was reported by the minority of the services (38%). The most commonly reported problems were insufficient structure for child/adolescent care (83%), increasing patient demand (72%), housing referral for homeless (72%), excessive prescription demand (69%), short-term room overcrowding (59%), court orders for inpatient treatment (59%), lack of vacancies for inpatients hospitalization (59%), and referral to primary care (56%). CONCLUSIONS: Similar to the United States, the Brazilian psychiatric emergency units are decreasing and encompass the shortcomings of the Brazilian mental health care network.


Assuntos
Serviços de Emergência Psiquiátrica , Transtornos Mentais , Adolescente , Brasil/epidemiologia , Criança , Estudos Transversais , Serviço Hospitalar de Emergência , Hospitalização , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Estados Unidos
8.
Rev. Assoc. Med. Bras. (1992) ; 68(5): 622-626, May 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1376174

RESUMO

SUMMARY OBJECTIVES: This study aimed to identify the infrastructure (e.g., availability, resources, and staff), basic metrics, and problems (e.g., network, overcrowding, resources, and infrastructure) of the psychiatric emergency services in Brazil. METHODS: This is a cross-sectional study assessing psychiatric services (n=29) listed by the Brazilian Psychiatric Association in 2019. RESULTS: Almost all the units reported 24 h/7-day availability having psychiatrists, nurses, and social workers, with 8.8 (SE=2.2) and 2.8 (SE=0.3) consultations and hospitalizations per day, respectively. Separated room for contention was reported by the minority of the services (38%). The most commonly reported problems were insufficient structure for child/adolescent care (83%), increasing patient demand (72%), housing referral for homeless (72%), excessive prescription demand (69%), short-term room overcrowding (59%), court orders for inpatient treatment (59%), lack of vacancies for inpatients hospitalization (59%), and referral to primary care (56%). CONCLUSIONS: Similar to the United States, the Brazilian psychiatric emergency units are decreasing and encompass the shortcomings of the Brazilian mental health care network.

9.
Trends psychiatry psychother. (Impr.) ; 41(2): 121-127, Apr.-June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1014735

RESUMO

Abstract Objectives To assess the sociodemographic and diagnostic profile of data related to psychiatric readmissions to the psychiatric ward at Hospital Estadual Mário Covas between January 2008 and September 2015, in order to investigate the possible correlation between the rate of admission and readmission and the presence or absence of a discharged patient unit or other outpatient treatment unit. Methods This was a cross-sectional, descriptive study. Data on patients readmitted during the study period were sourced from a statistical analysis of the Hospital Estadual Mário Covas database using STATA 11.0. Results During the study period, hospitalization rates decreased, while the readmission rates increased over the years, at a total of 662 readmissions. This rise in readmissions had no correlation with the presence of a discharged patient unit or other outpatient unit. Women comprised the majority of the sample, with a mean age of 42; the most prevalent disorder among women was bipolar affective disorder, while among men it was schizophrenia. The length of hospitalization increased over time, with a maximum mean time of 23 days in 2015. Most of the patients were referred from Santo André as well as from hospitals in São Paulo. Conclusion The increase in the rate of readmissions over the years suggests that the mental healthcare model may have shortcomings along the chain. It is important to understand the epidemiological profile and chain of events that led to repeated hospitalizations in order to design new strategies and approaches to care so as to keep the patients stabilized.


Resumo Objetivos Obter o perfil sociodemográfico e diagnóstico dos pacientes reinternados no Hospital Estadual Mário Covas entre janeiro de 2008 e setembro de 2015, com o intuito de investigar a possível relação entre as taxas de admissão e readmissão e a existência ou ausência do serviço para pacientes de alta clinica do hospital ou de outros serviços. Métodos Este foi um estudo descritivo transversal. Os dados foram obtidos do Hospital Estadual Mário Covas e analisados pelo programa STATA 11.0 Resultados Durante o período do estudo, as taxas de hospitalização diminuíram, enquanto as taxas de readmissão aumentaram progressivamente, com um total de 662 reinternações. O aumento dessas reinternações não teve relação com a presença da unidade pós-alta hospitalar do próprio hospital ou de outros serviços. A maioria dos pacientes era composta de mulheres, com idade média de 42 anos; o principal diagnóstico entre mulheres foi o transtorno afetivo bipolar, enquanto que para homens foi a esquizofrenia. O tempo de hospitalização aumentou com os anos, com uma média máxima em 2015 de 23 dias. A maior parte dos pacientes era referenciado de Santo André e outros hospitais de São Paulo. Conclusão O aumento das taxas de reinternação ao longo dos anos sugere que o sistema de cuidado mental tem deficiências em sua prática. É importante entender o perfil epidemiológico e a cascata de eventos que levam a rehospitalizações e, assim, traçar novas estratégias e abordagens de cuidado, mantendo os pacientes estabilizados.


Assuntos
Humanos , Masculino , Feminino , Adulto , Readmissão do Paciente/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Transtornos Mentais/terapia , Unidade Hospitalar de Psiquiatria , Brasil , Fatores Sexuais , Estudos Transversais , Pessoa de Meia-Idade
10.
Trends Psychiatry Psychother ; 41(2): 121-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843963

RESUMO

OBJECTIVES: To assess the sociodemographic and diagnostic profile of data related to psychiatric readmissions to the psychiatric ward at Hospital Estadual Mário Covas between January 2008 and September 2015, in order to investigate the possible correlation between the rate of admission and readmission and the presence or absence of a discharged patient unit or other outpatient treatment unit. METHODS: This was a cross-sectional, descriptive study. Data on patients readmitted during the study period were sourced from a statistical analysis of the Hospital Estadual Mário Covas database using STATA 11.0. RESULTS: During the study period, hospitalization rates decreased, while the readmission rates increased over the years, at a total of 662 readmissions. This rise in readmissions had no correlation with the presence of a discharged patient unit or other outpatient unit. Women comprised the majority of the sample, with a mean age of 42; the most prevalent disorder among women was bipolar affective disorder, while among men it was schizophrenia. The length of hospitalization increased over time, with a maximum mean time of 23 days in 2015. Most of the patients were referred from Santo André as well as from hospitals in São Paulo. CONCLUSION: The increase in the rate of readmissions over the years suggests that the mental healthcare model may have shortcomings along the chain. It is important to understand the epidemiological profile and chain of events that led to repeated hospitalizations in order to design new strategies and approaches to care so as to keep the patients stabilized.


Assuntos
Tempo de Internação/estatística & dados numéricos , Transtornos Mentais/terapia , Readmissão do Paciente/estatística & dados numéricos , Adulto , Brasil , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Unidade Hospitalar de Psiquiatria , Fatores Sexuais
11.
Subst Use Misuse ; 52(14): 1809-1822, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-28742414

RESUMO

This review aims to summarize neuroimaging studies in order to better understand the neural correlates of depressive symptoms in tobacco smokers. Using the keywords "depressive OR depression" AND "tobacco OR nicotine OR smok* OR cigarette" AND "neuroimage OR magnetic resonance OR smri OR structural magnetic resonance OR fmri OR functional magnetic resonance OR pet OR positron emission tomography", literature search was conducted in PubMed, Web of Science and PsycINFO databases. The first and the last author read the abstracts of all the studies found in the search (n = 179). The inclusion and exclusion criteria were applied and 150 articles were excluded. Then, both authors assessed the remaining 29 studies for eligibility and 16 studies were included in the present review. In the phase of active/chronic smoking, depressive symptoms are characterized as comorbidity related to an enhancement of dopamine release, and smokers have decreased Monoamine oxidase A (MAO-A). Stimuli-related functional magnetic resonance imaging (Stimuli-fMRI) studies also show that there is a positive correlation between the level of depressive symptoms and a greater response to general negative stimuli in active/chronic smokers. In the withdrawal phase, depressive symptoms are related to the withdrawal syndrome and increased MAO-A. Stimuli-fMRI studies show that there is a negative correlation between level of depressive symptoms and reactivity to negative stimuli in recent abstinent smokers. Major areas of the reward system such as the striatum and areas related to impulse control are activated to a greater extent in depressive smokers compared to non-depressed smokers.


Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo/fisiopatologia , Imageamento por Ressonância Magnética , Fumantes/psicologia , Fumar/efeitos adversos , Correlação de Dados , Transtorno Depressivo/psicologia , Dopamina/metabolismo , Humanos , Monoaminoxidase/metabolismo , Nicotina/efeitos adversos , Fumar/fisiopatologia , Abandono do Hábito de Fumar , Síndrome de Abstinência a Substâncias
12.
Curr Med Res Opin ; 30(4): 695-709, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24289141

RESUMO

OBJECTIVE: The purpose of this prospective study was to evaluate the effects of switching from oral risperidone to flexibly dosed oral paliperidone extended-release (ER) in Brazilian adults with schizophrenia because of lack of efficacy, intolerability, or nonadherence after a minimum trial of 30 days on adequate (labeled) doses of oral risperidone, according to individual clinical judgment. RESEARCH DESIGN AND METHODS: Subjects with Positive and Negative Syndrome Scale total scores above 78, and/or intolerable adverse effects, with risperidone received open-label paliperidone ER 3 to 12 mg daily for 26 (main phase) to 52 (extension phase) weeks. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01010776. RESULTS: The intent-to-treat (efficacy) populations comprised 213 subjects in the main phase and 159 in the extension phase. Of 213 subjects with baseline and post-baseline efficacy data, 154 (72.3%) switched from risperidone to paliperidone ER because of a lack of efficacy and 59 (27.7%) because of tolerability issues, according to individual clinical judgment. Paliperidone ER significantly (p < 0.0500) improved a broad spectrum of efficacy endpoints from baseline, as early as the first post-baseline visit (Visit 2; 4 weeks) and persisting through 26 to 52 weeks. On most efficacy endpoints, function improved from baseline to the first post-baseline visit (week 4) and remained significantly improved compared to baseline at each visit for paliperidone ER treatment, at weeks 8, 13, 26, 39, 26, and 52; data are reported herein mainly for 26 and 52 weeks compared to baseline. Significant improvements from baseline were observed for the Positive and Negative Syndrome Scale total score and subscale scores (each p < 0.0001 at 26 and 52 weeks vs. baseline); and personal and social functioning (p < 0.0001 at 26 and 52 weeks). Paliperidone ER also significantly improved health-related quality of life (Short-Form 36) from baseline, particularly on the Mental Component Summary (p = 0.0011 at 26 weeks and p = 0.0019 at 52 weeks). Treatment with paliperidone ER also significantly improved (vs. baseline) sleep quality (according to decreases on the Pittsburgh Sleep Quality Index; p < 0.0001 at each visit vs. baseline) and disease severity (Clinical Global Impression-Severity; p < 0.0001 at each visit vs. baseline). Paliperidone ER was well tolerated. Adverse events occurring in at least 10% of subjects in either phase were insomnia (14.9% in the main phase and 8.8% in the extension phase); increased body weight (10.7% and 12.6%, respectively); and anxiety (10.7% and 2.5%). Most of these adverse events were: 1) rated as mild or moderate; 2) did not prompt interventions such as paliperidone ER dose adjustment or interruption; and 3) decreased in frequency from the main to the extension phase. CONCLUSIONS: Oral paliperidone ER is a rational treatment alternative for patients with schizophrenia whose antipsychotic regimens are switched because of unsuccessful treatment with oral risperidone according to individual clinical judgment. Study limitations included the open-label study design, lack of placebo, and use of subjective clinical judgment to determine lack of efficacy, intolerability, or nonadherence with oral risperidone.


Assuntos
Isoxazóis/administração & dosagem , Pirimidinas/administração & dosagem , Qualidade de Vida , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Administração Oral , Adulto , Preparações de Ação Retardada , Feminino , Humanos , Isoxazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Palmitato de Paliperidona , Satisfação do Paciente , Estudos Prospectivos , Pirimidinas/efeitos adversos , Risperidona/efeitos adversos , Índice de Gravidade de Doença
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