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.

Objective: To present the essential guidelines for pharmacological management of patients with psychomotor agitation in Brazil. Methods: This is a systematic review of articles retrieved from the MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and SciELO databases published from 1997 to 2017. Other relevant articles in the literature were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools. Results: Of 5,362 articles retrieved, 1,731 abstracts were selected for further reading. The final sample included 74 articles that met all inclusion criteria. The evidence shows that pharmacologic treatment is indicated only after non-pharmacologic approaches have failed. The cause of the agitation, side effects of the medications, and contraindications must guide the medication choice. The oral route should be preferred for drug administration; IV administration must be avoided. All subjects must be monitored before and after medication administration. Conclusion: If non-pharmacological strategies fail, medications are needed to control agitation and violent behavior. Once medicated, the patient should be monitored until a tranquil state is possible without excessive sedation. Systematic review registry number: CRD42017054440.

Abstract Introduction Brazil is the world’s biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence. Method We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil’s largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained. Results Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%). Conclusion Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.

Resumo Introdução O Brasil é o maior consumidor mundial de crack, e a dependência é um grande problema de saúde pública. Este é o primeiro estudo a investigar a prevalência de adulterantes potencialmente nocivos presentes em amostras de cabelo de pacientes brasileiros com dependência de crack. Métodos Foram avaliados adulterantes em amostras de cabelos extraídos por conveniência de 100 pacientes internados na unidade de observação de 48 horas do Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), o maior centro de tratamento de dependência do Brasil. Uma análise transversal foi realizada com os dados obtidos. Resultados Foram encontrados adulterantes em 97% das amostras de cabelo analisadas. O adulterante mais prevalente foi a lidocaína (92%), seguida da fenacetina (69%) e levamisol (31%). Conclusão Os adulterantes foram amplamente prevalentes em amostras de cabelo de usuários de crack tratados no CRATOD: pelo menos um adulterante estava presente em praticamente todas as amostras de cabelo coletadas. Isso aponta para a necessidade de monitorar os efeitos adversos no ambiente clínico, a fim de proporcionar a esse grupo de pacientes de alto risco cuidados imediatos e efetivos relacionados às complicações agudas e crônicas associadas a esses adulterantes.

Objective: To present the essential guidelines for non-pharmacological management of patients with psychomotor agitation in Brazil. Methods: These guidelines were developed based on a systematic review of articles published from 1997 to 2017, retrieved from MEDLINE (PubMed), Cochrane Database of Systematic Review, and SciELO. Other relevant articles identified by searching the reference lists of included studies were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools. Results: We initially selected 1,731 abstracts among 5,362 articles. The final sample included 104 articles that fulfilled all the inclusion criteria. The management of agitated patients should always start with the least coercive approach. The initial non-pharmacological measures include a verbal strategy and referral of the patient to the appropriate setting, preferably a facility designed for the care of psychiatric patients with controlled noise, lighting, and safety aspects. Verbal de-escalation techniques have been shown to decrease agitation and reduce the potential for associated violence in the emergency setting. The possibility of underlying medical etiologies must be considered first and foremost. Particular attention should be paid to the patient’s appearance and behavior, physical signs, and mental state. If agitation is severe, rapid tranquilization with medications is recommended. Finally, if verbal measures fail to contain the patient, physical restraint should be performed as the ultimate measure for patient protection, and always be accompanied by rapid tranquilization. Healthcare teams must be thoroughly trained to use these techniques and overcome difficulties if the verbal approach fails. It is important that healthcare professionals be trained in non-pharmacological management of patients with psychomotor agitation as part of the requirements for a degree and graduate degree. Conclusion: The non-pharmacological management of agitated patients should follow the hierarchy of less invasive to more invasive and coercive measures, starting with referral of the patient to an appropriate environment, management by a trained team, use of verbal techniques, performance of physical and mental assessment, use of medications, and, if unavoidable, use of the mechanical restraint. Systematic review registry number: CRD42017054440.

Abstract Introduction: The recovery housing (RH) program was initiated in São Paulo with the objective of providing treatment for substance use disorders and addressing users’ housing and employment problems. The purpose of this study was to describe the model based on its first 11 months of operation, it was launched in June 2016 in Brazil. Method: We carried out a retrospective analysis of the records of all subjects treated in the RH of the Restart Program (Programa Recomeço) since its creation, from June 2016 to May 2017. Results: Sixty-nine subjects were included. Thirty-five (51%) remained in the household until the end of treatment or were reinserted in society. Thirty-four (49%) presented recurrence during their stay, of which 16 (47%) volunteered for treatment in a therapeutic community or psychiatric hospital, 8 (23.5%) chose to continue with outpatient treatment only, 6 (17.7%) returned to their families and continued to receive outpatient treatment, and 4 (11.8%) discontinued the treatment. Of the 35 subjects who completed the RH program, 28 (80%) were in employment and 7 (20%) received governmental support for permanent disability on medical or psychiatric grounds. Conclusion: RH can be an important component of integrated care and is used in several countries. Although controversial, the use of urine tests to control relapse seems to have a positive impact on adherence to treatment and maintenance of abstinence. These preliminary findings corroborate, with clear limitations, the evidence available in the literature showing that RH programs are effective for the treatment of addictions.

Resumo Introdução: O Programa Moradia Monitorada (MM) foi iniciado em São Paulo com o objetivo de prover tratamento para transotrnos de uso de substâncias e problemas relacionados a moradia e emprego. O objetivo do presente estudo foi descrever o modelo com base nos primeiros 11 meses de operação (o programa foi lançado em junho de 2016 no Brasil). Métodos: Realizamos um estudo retrospectivo utilizando os registros de todos os indivíduos tratados no MM do Programa Recomeço desde a sua criação. Resultados: Sessenta e nove indivíduos foram incluídos. Trinta e cinco (51%) permaneceram no tratamento até o fim ou foram reinseridos socialmente com sucesso. Trinta e quatro sujeitos (49%) apresentaram recidiva durante a permanência. Destes, 16 (47%) se voluntariaram para tratamento em comunidades terapêuticas ou hospitais psiquiátricos, 8 (23,5%) escolheram permanecer apenas no tratamento ambulatorial, 6 (17.7%) retornaram para suas famílias e continuaram o tratamento em uma unidade ambulatorial próxima ao domicílio, e 4 (11.8%) descontinuaram o tratamento. Dos 35 pacientes que completaram o tratamento, 28 (80%) estavam empregados em serviço regular e 7 (20%) recebiam aposentadoria por questões clínicas e/ou psiquiátricas. Conclusão: O modelo MM pode ser um componente importante na via de cuidados integrados e é utilizado em vários países. Apesar de controverso, o uso de análise de urina para vigilância da recidiva e da recorrência parece ter um impacto positivo na adesão ao tratamento e na manutenção da abstinência. Nossos achados preliminares corroboram, com claras limitações, os resultados reportados previamente na literatura, de que os programas de MM são efetivos no tratamento da dependência química.

Objective: Work is considered one of the main forms of social organization; however, few individuals with schizophrenia find work opportunities. The purpose of this study was to evaluate the relationship between schizophrenia symptoms and job acquisition. Method: Fifty-three individuals diagnosed with schizophrenia from an outpatient treatment facility were included in an 18-month follow-up study. After enrollment, they participated in a prevocational training group. At the end of training (baseline) and 18 months later, sociodemographic, clinical data and occupational history were collected. Positive and negative symptoms (Positive and Negative Syndrome Scale – PANSS), depression (Calgary Depression Scale), disease severity (Clinical Global Impression – CGI), functionality (Global Assessment of Functioning – GAF), personal and social performance (Personal and Social Performance – PSP) and cognitive functions (Measurement and Treatment Research to Improve Cognition in Schizophrenia – MATRICS battery) were applied at baseline and at the end of the study. Results: Those with some previous work experience (n=19) presented lower scores on the PANSS, Calgary, GAF, CGI and PSP scales (p < 0.05) than those who did not work. Among those who worked, there was a slight worsening in positive symptoms (positive PANSS). Conclusions: Individuals with less severe symptoms were more able to find employment. Positive symptom changes do not seem to affect participation at work; however, this calls for discussion about the importance of employment support.

Objective: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population. Methods: Two reviewers independently searched for eligible studies and extracted outcome data using a structured form. Papers were retrieved from PubMed and ISI Web of Knowledge using the search term schizophrenia in combination with CNR1 or CB1 or cannabinoid receptor. Twenty-four articles met our inclusion criteria. We additionally present data from a study of our own comparing 182 patients with schizophrenia and 244 healthy controls. Results: No consistent evidence is demonstrated. Conclusion: Some seemingly positive association studies stress the need for further investigations of the possible role of endocannabinoid genetics in schizophrenia.

Summary Objective: To compare the risk of comorbid sexual addiction in a sample of individuals with a diagnosis of substance dependence, stratifying the sample by drug of choice as well as by mono versus polysubstance addiction. Method: All data were collected at Santa Casa de São Paulo, Brazil. The study sample comprised all alcohol or drug dependents admitted to the Addiction Treatment Unit between November 2013 and August 2014. A generalized linear model with a binomial distribution was performed to compare the odds of having a Sexual Addiction Screening Test (SAST) score greater than 6 points in the subgroups analyzed. Results: A total of 133 participants were included in our analysis, all reporting cocaine/crack and/or alcohol as drug of choice. Polysubstance addicts had a significant higher risk of a positive screening for sexual addiction compared to monosubstance addicts, age-sex adjusted odds ratios of sexual addiction being respectively 2.72 (95CI 1.1-6.71) and 0.37 (95CI 0.15-0.91). The odds of a SAST score greater than 6 was not statistically different between the cocaine/crack and alcohol groups, respectively 0.38 (95CI 0.14-1.02) and 2.67 (95CI 0.98-7.25). We found a significant relation between stronger drug addiction and greater levels of sexual addiction in the cocaine/crack group (p=0.0012), but not in the alcohol group. Conclusion: Our study reinforces the importance of assessing sexual behavior of drug addicts in clinical practice, especially considering users of multiple substances or with severe dependence.

Resumo Objetivo: Comparar o risco de dependência sexual em uma amostra de indivíduos com diagnóstico de dependência química, estratificados por droga de escolha e por dependência única ou de múltiplas substâncias. Método: Todos os dados foram coletados na Santa Casa de São Paulo, Brasil. A amostra estudada correspondeu a todos os indivíduos dependentes de álcool ou outras substâncias admitidos no Ambulatório de Dependência Química entre novembro de 2013 e agosto de 2014. Modelos lineares generalizados com distribuição binomial foram utilizados para comparar o risco de escores maiores que seis na Escala de Rastreamento para Dependência de Sexo (SAST) nos subgrupos analisados. Resultados: Foram analisados os dados de 133 pacientes usuários de cocaína/crack e/ou álcool. Usuários de múltiplas substâncias apresentaram risco significativamente maior de um screening positivo para dependência sexual comparados com usuários de uma única substância. Os odds ratios de dependência sexual ajustados por sexo e idade obtidos nos dois grupos foram, respectivamente, 2.72 (IC95% 1.1-6.71) e 0.37 (IC95% 0.15-0.91). O risco de dependência sexual entre usuários de cocaína/crack e álcool foi estimado, respectivamente, em 0.38 (IC95% 0.14-1.02) e 2.67 (IC95% 0.98-7.25), não indicando diferença significativa. Foi encontrada uma relação significativa entre severidade de dependência química e maiores níveis de dependência sexual entre dependentes de cocaína/crack, mas não de álcool. Conclusão: Nosso estudo reforça a importância de avaliar o comportamento sexual de dependentes químicos na prática clínica, especialmente considerando usuários de múltiplas substâncias, ou casos de maior severidade.

Abstract Objective: This study is a critical review analyzing occurrence of treatment-emergent mania (TEM) related to transcranial direct current stimulation (tDCS) and trigeminal nerve stimulation (TNS). Method: We present a systematic review of the literature on TEM related to tDCS and TNS treatment for major depressive disorder (MDD), conducted in accordance with the recommendations from Cochrane Group and the PRISMA guidelines. Results: Our search identified few reported episodes of TEM in the literature. In fact, we found 11 trials focused on treatment of MDD (seven controlled trials of tDCS and four trials of TNS, three open label and one controlled). We highlight the need for safety assessment in clinical research settings to establish with precision and in larger samples the risks inherent to the technique under investigation. Conclusion: Safety assessment is of fundamental importance in clinical research. TEM is a very important safety issue in MDD trials. Further and larger controlled trials will help to clarify both the safety and the clinical effects of combinations of pharmacotherapy and tDCS or TNS in daily clinical practice.

Resumo Objetivo: O presente estudo consiste em uma revisão e análise crítica da ocorrência de mania tratamento-emergente (TEM) relacionada a estimulação transcraniana por corrente contínua (ETCC) e estimulação do nervo trigêmeo (TNS). Método: Apresentamos uma revisão sistemática de literatura sobre TEM relacionada a ETCC e TNS no tratamento de transtorno depressivo maior (TDM), conduzida de acordo com as recomendações do Grupo Cochrane e protocolo PRISMA. Resultados: A pesquisa identificou poucos relatos de TEM na literatura. Na verdade, foram encontrados 11 ensaios clínicos com foco no tratamento de TDM (sete estudos controlados de ETCC e quatro de TNS, sendo três abertos e um controlado). Destacamos a necessidade de avaliações de segurança em pesquisas clínicas para se estabelecer com maior precisão e em amostras maiores os riscos inerentes à técnica sob investigação. Conclusão: Avaliação de segurança é fundamental na pesquisa clínica. A TEM é um efeito adverso importante no tratamento do TDM. Maiores ensaios clínicos controlados ajudarão a esclarecer os efeitos clínicos e a segurança da combinação de psicotrópicos e ETCC ou TNS.

Abstract Introduction: We report a transcranial direct current stimulation (tDCS) protocol over the dorsolateral prefrontal cortex (DLPFC) combined with cognitive training in schizophrenia. Method: We assessed psychotic symptoms in nine patients using the Positive and Negative Syndrome Scale (PANSS). All evaluations were scored at baseline, at the end of the intervention protocol, and during a 4-week follow-up. The tDCS protocol consisted of 10 consecutive sessions over 5-day periods. We placed the cathode over the right and the anode over the left DLPFC. For sham stimulation, we turned the device off after 60 seconds. Cognitive training consisted of the administration of N-back and sequence learning tasks. Results: We performed an analysis of covariance (ANCOVA) to adjust for the dependent variable PANSS, considering the interaction with baseline severity scores (p = 0.619). Mixed analysis of variance (ANOVA) showed no statistical significance between the groups regarding final PANSS scores. Conclusion: The results failed to demonstrate that the concomitant use of tDCS and cognitive training is effective to improve clinical outcomes in patients with schizophrenia. The present findings should be analyzed with care, considering the small sample size. Larger controlled trials on electric/cognitive stimulation should be produced in order to enhance therapeutic strategies in schizophrenia.

Resumo Introdução: Descrevemos os resultados de protocolo de estimulação transcraniana por corrente contínua (ETCC) sobre o córtex pré-frontal dorsolateral combinado a treinamento cognitivo para o tratamento de esquizofrenia. Métodos: Avaliamos os sintomas psicóticos em nove pacientes utilizando a Positive and Negative Syndrome Scale (PANSS). As avaliações foram realizadas antes, ao fim do protocolo de tratamento, e após 4 semanas de seguimento. O protocolo de ETCC consistiu em 10 sessões consecutivas em períodos de 5 dias. O cátodo foi posicionado à direita e o ânodo à esquerda sobre o córtex pré-frontal dorsolateral. Para estimulação simulada, o equipamento foi desligado após 60 segundos. O treinamento cognitivo consistiu na administração de tarefas N-back e aprendizado sequencial. Resultados: Utilizamos análise de covariância (ANCOVA) ajustada à variável dependente PANSS, considerando a interação com a gravidade antes da ETCC (p = 0.619). A análise de variância (ANOVA) não mostrou diferença significativa entre os grupos em relação à PANSS final. Conclusão: Os resultados falharam em demonstrar que o uso concomitante de ETCC e treinamento cognitivo é efetivo na melhora do desfecho clínico em pacientes com esquizofrenia. Os achados devem ser avaliados com cuidado, considerando a amostra pequena. Estudos maiores sobre estimulação elétrica/cognitiva devem ser produzidos a fim de melhorar estratégias terapêuticas na esquizofrenia.

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.

Introduction Transcranial magnetic stimulation (TMS) is a promising non-pharmacological intervention for posttraumatic stress disorder (PTSD). However, randomized controlled trials (RCTs) and meta-analyses have reported mixed results. Objective To review articles that assess the efficacy of TMS in PTSD treatment. Methods A systematic review using MEDLINE and other databases to identify studies from the first RCT available up to September 2015. The primary outcome was based on PTSD scores (continuous variable). The main outcome was Hedges' g. We used a random-effects model using the statistical packages for meta-analysis available in Stata 13 for Mac OSX. Heterogeneity was evaluated with I2 (> 35% for heterogeneity) and the χ2 test (p < 0.10 for heterogeneity). Publication bias was evaluated using a funnel plot. Meta-regression was performed using the random-effects model. Results Five RCTs (n = 118) were included. Active TMS was significantly superior to sham TMS for PTSD symptoms (Hedges' g = 0.74; 95% confidence interval = 0.06-1.42). Heterogeneity was significant in our analysis (I2 = 71.4% and p = 0.01 for the χ2 test). The funnel plot shows that studies were evenly distributed, with just one study located marginally at the edge of the funnel and one study located out of the funnel. We found that exclusion of either study did not have a significant impact on the results. Meta-regression found no particular influence of any variable on the results. Conclusion Active TMS was superior to sham stimulation for amelioration of PTSD symptoms. Further RCTs with larger sample sizes are fundamental to clarify the precise impact of TMS in PTSD.

Introdução A estimulação magnética transcraniana (EMT) é uma intervenção não farmacológica promissora no tratamento de transtorno de estresse pós-traumático (TEPT). No entanto, estudos controlados e metanálises apresentaram resultados conflitantes até o momento. Objetivo Revisar os artigos sobre a eficácia da EMT para o tratamento de TEPT. Métodos Conduzimos uma revisão sistemática da literatura no MEDLINE para identificar estudos controlados e randomizados publicados até setembro de 2015. O desfecho primeiro foi baseado nas escalas de gravidade de TEPT como variáreis contínuas. O desfecho principal foi o g de Hedges. Utilizamos o modelo de efeito randômico com as análises estatísticas para metanálise do Stata 13 para Mac OSX. A heterogeneidade foi avaliada com o I2 (> 35% para heterogeneidade) e o teste do χ2 (p < 0,01 para heterogeneidade). Viés de publicação foi avaliado utilizando-se o gráfico do funil. Realizamos metarregressões com modelo de efeito randômico. Resultados Cinco estudos foram incluídos. A EMT ativa foi superior ao placebo para o tratamento de TEPT (g de Hedges = 0,74; intervalo de confiança 95% = 0,06-1,42). A heterogeneidade entre os estudos foi significativa em nossa análise (I2 = 71,4% e p = 0,01 para o teste do χ2). O gráfico do funil nos mostrou estudos simetricamente distribuídos, com apenas um estudo localizado marginalmente ao gráfico e um estudo localizado fora do funil. Encontramos que a exclusão de cada estudo não alterou significativamente o resultado final. A metarregressão não mostrou influência de nenhuma variável no resultado. Conclusões A estimulação ativa de EMT foi superior à estimulação simulada para melhora dos sintomas de TEPT. Novos estudos randomizados e controlados por simulação são necessários para esclarecer com melhor precisão o impacto da EMT no TEPT.