INTRODUÇÃO: Os transtornos psiquiátricos são altamente prevalentes e têm sido associados ao maior uso de serviços e de medicamentos. Entretanto resultados do World Health Organization (WHO) World Mental Health (WHM) Surveys, conduzidos em diversos países, têm apresentado baixas prevalências de uso de psicofármacos entre sujeitos com diagnóstico de transtornos psiquiátricos no ano anterior à entrevista. OBJETIVOS: Estimar a prevalência, o padrão, e os fatores associados ao uso de psicofármacos em amostra da população geral e entre sujeitos com diferentes diagnósticos para doenças psiquiátricas, de acordo com DSM-IV. MÉTODOS: Os dados são provenientes do São Paulo Megacity Mental Health Survey (SPMHS), segmento brasileiro do estudo World Mental Health Survey (WMH survey). O WMH survey é uma iniciativa da Organização Mundial da Saúde (OMS), da Universidade de Harvard e Universidade de Michigan, que vem sendo realizada em mais de 28 centros de pesquisa no mundo. O São Paulo Megacity Mental Health Survey é um estudo de corte transversal, de base populacional, desenhado para avaliar a morbidade psiquiátrica em uma amostra representativa da população geral, com 18 anos ou mais, residentes na Região Metropolitana de São Paulo. Uma amostra de 5.037 indivíduos (taxa de resposta: 81,3%) foi entrevistada por leigos treinados, utilizando a versão do Composite International Diagnostic Interview para o World Mental Health Survey, elaborado para gerar diagnósticos de acordo com o DSM-IV. O foco do presente estudo foi uma subamostra de 2.935 entrevistados, os quais foram avaliados com a versão longa da entrevista e que foram questionados sobre psicofármacos prescritos no ano anterior à entrevista para \"problemas com emoções, nervos, saúde mental, uso de substâncias, energia, concentração, sono ou a capacidade de lidar com o estresse\". Os dados foram ponderados para ajustar a subamostragem dos não casos dessa subamostra e para ajustar as discrepâncias residuais entre as distribuições amostrais e populacionais de uma série de variáveis sociodemográficas, garantindo, assim, a representatividade dessa subamostra. RESULTADOS: Apenas 6,13% dos respondentes relataram o uso de psicofármacos no ano anterior à entrevista. Os hipnóticos e sedativos (incluindo os benzodiazepínicos) (3,63%) e os antidepressivos (3,46%) foram os mais comumente relatados, enquanto os estabilizadores de humor (0,64%) e os antipsicóticos (0,61%) foram pouco frequentes. Ser do sexo feminino (OR= 2,55; 95% IC=1,58-4,11), avançar da idade, escolaridade abaixo do nível superior e ter maior renda foram fatores associados ao maior uso de psicofármacos, assim como ter comorbidades e transtornos graves. A prevalência de transtornos psiquiátricos de acordo com os critérios do DSM-IV/WMH-CIDI no ano anterior à entrevista foi 29,49%. Entretanto, somente 13,75% dos sujeitos com diagnóstico de transtorno psiquiátrico no ano anterior à entrevista, 24,93% com transtorno de humor, 14,43% com transtorno de ansiedade e, aproximadamente, 10% com transtorno por uso de substância e com transtorno de controle do impulso relataram uso de psicofármacos no mesmo período. Respondentes sem diagnóstico também reportaram uso de psicofármacos (2,94%). O uso de antidepressivos (9,10%) e de hipnóticos e sedativos (7,81%) foi pouco frequente naqueles com diagnóstico, apresentando a seguinte distribuição, respectivamente: sujeitos com transtorno de humor (17,94% e 14,70%), ansiedade (9,04% e 8,08%), controle de impulso (6,76% e 5,80%) e por uso de substâncias (5,08% e 7,86%). O uso de psicofármacos foi maior entre sujeitos que apresentaram três transtornos ou mais (26,91%) quando comparado aos que apresentaram dois (15,21%) ou um transtorno (8,96%). Entre os sujeitos com transtornos considerados leve, de moderada gravidade e grave, a prevalência de uso de psicofármacos foi 6,60%, 10,68% e 23,77%, respectivamente. Entretanto aproximadamente 75% casos graves e com três ou mais transtornos, permaneceram sem tratamento farmacológico. CONCLUSÃO: Os resultados sugerem que a maioria dos sujeitos com transtornos psiquiátricos ativos não estão recebendo tratamento farmacológico para seus transtornos psiquiátricos na Região Metropolitana de São Paulo. Políticas públicas poderiam aumentar o acesso aos cuidados de saúde adequado, particularmente entre sujeitos com transtornos graves e comorbidades / INTRODUCTION: Mental Disorders are highly prevalent and have been associated with high use of health services and medications. However results of the World Health Organization (WHO) World Mental Health (WHM) Surveys carried out in several countries have found low prevalence rates of psychotropic medication among those with 12-month disorders. OBJECTIVES: To estimate the prevalence, pattern, and associated factors with the use of psychotropic medication in a sample in the general population and, within this sample, among those with different diagnoses for psychiatric disorders, according to DSM-IV. METHODS: Data were from the São Paulo Megacity Mental Health Survey (SPMHS), the Brazilian segment of the World Mental Health (WMH) Survey Initiative, coordinated by the World Health Organization and Harvard University, which has been held in more than 28 research centers in the world. The São Paulo Megacity Mental Health Survey is a cross-sectional population-based study, designed to evaluate psychiatric morbidity in a representative sample in the general population, aged 18 years or more, living in the São Paulo Metropolitan Area. A sample of 5,037 individuals (response rate: 81.3%) was assessed by trained lay interviewers using the World Mental Health version of the Composite International Diagnostic Interview, designed to generate DSM-IV diagnoses. The focus of the current report was a subsample of 2,935 subjects to whom the long version of the interview was applied and were asked about prescription medicines that used in the previous12 months for \"problems with emotions, nerves, mental health, substance use, energy, concentration, sleep or ability to cope with stress\". Data were weighted to adjust the undersampling of long interview respondents non-cases and to adjust residual discrepancies between the sample and population distributions of a range of sociodemographic variables. RESULTS: Only 6.13% of the respondents reported psychotropic medication use in the previous year the interview. Hypnotics and sedatives (including benzodiazepines) (3.63%) and antidepressants (3.46%) were the most commonly reported, while mood stabilizers (0.64%) and antipsychotics (0.61%) were used less frequently. In the general population of the SPMHS, be female gender (OR= 2.55; 95% IC=1.58-4.11), older, education low level high and higher income were associated the higher psychotropic medication use, well as have comorbidity and serious disorders. The 12-month prevalence of DSM-IV/WMH-CIDI disorder was 29.49%. However, only 13.75% of those with 12-month disorders, 24.93% among those with mood disorder, 14.43% in those with anxiety disorder and, approximately 10% impulse-control disorder and substance use disorder reported psychotropic medication use in the same period. Respondents without diagnosis also reported psychotropic medication use (2.94%). Antidepressants (9.10%) and hypnotics and sedatives (7.81%) were commonly reported, with the following distribution, respectively: subjects with mood disorder (17.94% and 14.70%), anxiety (9.04 % and 8.08%), impulse control (6.76% and 5.80%), and substance use (5.08% and 7.86%). Psychotropic medication use was higher among the respondents with three or more disorders (26.91%), when compared with those with two (15.21%) or with one disorder (8.96%). Among the respondents with mild, moderate, or severe disorders, the prevalence of Psychotropic medication use was 6.60%, 10.68%, and 23.77%, respectively. However approximately 75% severe cases and comorbidities, remained without pharmacologic treatment. CONCLUSION: These findings suggest that the majority of individuals diagnosed with an active mental disorder are not being treated with psychotropic medication in the São Paulo Metropolitan Area. Public policies should increase access to appropriate care, particularly among subjects with serious disorders and comorbidities

Environmental pollution by pharmaceuticals is an issue of concern that is currently attracting attention around the world. Although environmental effects of pharmaceutical contaminants are not yet well documented, studies have shown that these substances may have the potential to disrupt the biotic component of an ecosystem. Particularly worrisome contaminants are the neuroactive pharmaceuticals which have the potentiality to induce behavioral modifications in non-target species. In the present study, I examined the effects of a benzodiazepine anxiolytic pharmaceutical (oxazepam) on the behavior of Atlantic salmon (Salmo salar) juveniles (fry). The hypothesis of this study was that oxazepam reduces the anxiety-like behavior of the Atlantic salmon juveniles. To test the hypothesis and assess the impact of oxazepam exposure on Atlantic salmons fry behavior, two different concentrations of this drug; a low-level (1.9 ug L-1) and a high-level concentration (1000 ug L-1) were used. Exposures lasted for 48 hours and afterwards, the fish were recorded to evaluate their behavioral responses. The results of this study reveal that oxazepam in a high concentration (1000 ug L-1 ) alters specific behavioral endpoints related to the fitness (feeding/predator avoidance) of Atlantic salmons fry. Individuals exposed to the high oxazepam concentration exhibited significant lower average speed and acceleration as well as they traveled a shorter mean distance compared to the unexposed (control) individuals. These findings confirm the hypothesis and show that psychotropic pharmaceutical contaminants modify animal behaviors, which can ultimately lead to ecological consequences. However, the concentration that generated behavioral effects in this study was three magnitudes higher than concentrations measured in the environment and thus, should not be viewed representative for oxazepam contaminated ecosystems.

A new analytical methodology was developed in order to investigate the presence of five psychoactive drugs (anxiolytic and antiepileptics), namely, bromazepam, carbamazepine, clonazepam, diazepam, and lorazepam in the effluent of the University Hospital of Santa Maria (HUSM) of the Federal University of Santa Maria (UFSM), since these compounds are widely used in the treatment of anxiety and epilepsy. Samples were collected from two points to check the concentration of the compounds: Point A (Emergency) and point B (General Effluent - which covers the Central Library and HUSM). The method of clean-up/pre-concentration by solid phase extraction (SPE) was used to assess the occurrence of anxiolytic and antiepileptic drugs in the effluent of HUSM. Three methods were developed and validated to determine these compounds: i) high performance liquid chromatography with ultraviolet detection (HPLCUV), ii) high performance liquid chromatography with detection by mass spectrometry (LC-MS), and iii) liquid chromatography-ion trap-tandem mass spectrometry with electrospray ionization (LCMS/ MS_Qtrap). Among the methods evaluated, LC-MS/MS_Qtrap with electrospray in positive mode yielded better results. The detection limit (LOD, S/N ≥3) for lorazepam and bromazepam was 4.90±0.95 ng L-1 and for carbamazepine, clonazepam and diazepam, 6.10±1.50 ng L-1. The limit of quantification (LOQ, S/N ≥10) was 30.00±1.10 ng L-1 bromazepam , clonazepam and lorazepam; 50.00±1.81 ng L-1, carbamazepine; and 40.00±0.98 ng L-1 diazepam. The linear range of the assay (LC-MS/MS_Qtrap) was 30-1500 ng L-1 for bromazepam; 50-2500 ng L-1, carbamazepine; 30-2500 ng L-1, clonazepam; 40-2500 ng L-1, diazepam; and 30 - 2000 ng L-1, lorazepam. The correlation coefficient (R2>0.997) for all compounds. The effectiveness of the methodology was verified by recovery with the fortification of three concentration levels in triplicate samples of hospital effluent. The average recovery rates observed were: 93.9±2.1% for bromazepam; 92.6±4.2%, carbamazepine; 93.9%±3.0 clonazepam; 91.8%±6.0 for diazepam; and 93.8%±4.3 for lorazepam. The mean concentrations of psychiatric drugs detected in the effluent of the Emergency and General Effluent were respectively: 195.0±6.4 ng L-1 and 137.1±7.0 ng L-1 for bromazepam; 589.6±6.1 ng L-1, and 460.7±9.3 ng L-1, carbamazepine; 645.0±0.3 ng L-1 and 571.0± 9.9ng L-1, diazepam; 95.7±6.7 ng L-1 and 42.4±4.2 ng L-1 lorazepam; and 134.3 ± 9.8 ng L-1 and 56.9 ± 9.9 ng L-1 clonazepam. The identification of metabolites in the hospital effluent was made through (LCMS/ MS_Qtrap). The metabolites identified were: 3-hydroxybromazepam (bromazepam), 7- aminoclonazepam (clonazepam), carbamazepine 10,11-epoxide, 10-dihydroxy-10,11- dihydrocarbamazepine, iminoquinone, 2-hydroxy-carbamazepine and acridone (carbamazepine), and nordiazepam, oxazepam and temazepam (diazepam), and their fragmentation pathways were proposed. Was performed a preliminary risk assessment of anxiolytic and antiepileptic drugs with the aid of literature data and found that the carbamazepine and diazepam compounds showed the highest risk (0.85 and 0.90, respectively) among the compounds analyzed. According to the results we can say that they present medium risk requiring more attention in terms of toxicity. However, no literature data were found on the Predicted No Effect Concentration (PNEC) for bromazepam, lorazepam, clonazepam, not allowing the calculation of risk quotient (RQ) for these compounds.Therefore, we observed the occurrence of anxiolytic and antiepileptic drugs in the effluent of HUSM at concentrations in the order of ng L-1. The analytical method for LC-MS/MS_Qtrap developed for the determination of psychoactive drugs (bromazepam, carbamazepine, clonazepam, diazepam and lorazepam) in hospital effluent proved to be sensitive and selective, eliminating laborious sample handling and requiring chromatographic run of just 15 minutes. The occurrence of these drugs and environmental risks associated demonstrate the need for more efficient treatment for the hospital effluent. / Uma nova metodologia analítica foi desenvolvida com a finalidade de investigar a presença de cinco fármacos psicoativos (ansiolíticos e antiepilépticos): bromazepam, carbamazepina, clonazepam, diazepam e lorazepam no efluente do Hospital Universitário de Santa Maria (HUSM) da Universidade Federal de Santa Maria (UFSM), visto que estes compostos são amplamente utilizados no tratamento da ansiedade e da epilepsia. As amostras foram coletadas de dois pontos para a verificação da concentração dos compostos: o Ponto A (efluente do PAHUSM) e o ponto B (efluente geral que abrange o HUSM e a Biblioteca Central). Utilizou-se um método de clean-up/pré-concentração por extração em fase sólida, para avaliar a ocorrência de ansiolíticos e antiepilépticos no efluente do HUSM. Deste modo, três métodos para determinar estes compostos foram desenvolvidos e validados: i) cromatografia líquida de alta eficiência com detecção por ultravioleta (HPLC-UV), ii) cromatografia líquida de alta eficiência com detecção por espectrometria de massa (LC-MS) e iii) cromatografia líquida acoplada a espectrometria de massa com ionização por eletronebulização e armadilha de íons (LC-MS/MS_Qtrap). Dentre os métodos avaliados, o LC-MS/MS_Qtrap com eletronebulização no modo positivo obteve melhores resultados. O limite de detecção (LOD, S/N ≥3) para bromazepam e lorazepam foi 4,90±0,95 ng L-1 e, para carbamazepina, clonazepam e diazepam, 6,10±1,50 ng L-1. O limite de quantificação (LOQ, S/N ≥10) foi de 30,00±1,10 ng L-1, para bromazepam, clonazepam e lorazepam; carbamazepina, 50,00±1,81 ng L-1 e, diazepam, 40,00±0,98 ng L-1. A faixa linear do método (LC-MS/MS_Qtrap) para bromazepam foi de 30-1500 ng L-1, para carbamazepina 50-2500 ng L-1; clonazepam de 30-2500 ng L-1, diazepam 40-2500 ng L-1 e para lorazepam foi de 30-2000 ng L-1. O coeficiente de correlação (R2 >0,997) para todos os compostos. A eficiência da metodologia foi verificada através da recuperação com a fortificação em três níveis de concentração em triplicata de amostras de efluente hospitalar. As taxas de recuperação média constatadas foram: para bromazepam 93,9%±2,1; carbamazepina 92,6%±4,2; clonazepam 93,9%±3,0; diazepam 91,8%±6,0 e lorazepam foi de 93,8%±4,3. As concentrações médias das drogas psiquiátricas detectadas no efluente do PA-HUSM e efluente geral foram respectivamente: bromazepam, 195,0±6,4 ng L-1 e 137,1±7,0 ng L-1; carbamazepina, 589,6±6,1 ng L-1 e 460,7±9,3 ng L-1, diazepam, 645,0±0,3 ng L-1 e 571,0±9,9 ng L-1, lorazepam, 95,7±6,7 ng L-1 e 42,4±4,2 ng L-1 e clonazepam, 134,3±9,8 ng L-1 e 56,9±9,9 ng L-1. A identificação dos metabólitos no efluente hospitalar foi realizada através de LC-MS/MS_Qtrap. Os metabólitos identificados foram: 3-hidroxi-bromazepam (bromazepam), 7-amino-clonazepam (clonazepam), carbamazepina 10,11-epóxido, 10-dihidroxi-10,11-dihidrocarbamazepina, iminoquinona, 2-hidroxi-carbamazepina e acridona (carbamazepina), nordiazepam, oxazepam e temazepam (diazepam) e, seus caminhos de fragmentação foram propostos. Foi realizada uma avaliação de risco preliminar de ansiolíticos e antiepilépticos com o auxílio de dados da literatura e foi verificado que os compostos carbamazepina e diazepam apresentaram maior risco com Quociente de Risco teórico (0,85 e 0,90, respectivamente) entre os compostos analisados. De acordo com os resultados obtidos pode-se dizer que apresentam risco médio, requerendo maior atenção em termos de toxicidade. Entretanto, dados na literatura não foram encontrados sobre a Concentração Prevista que Não Causa Efeito (PNEC) para bromazepam, clonazepam e lorazepam, impossibilitando o cálculo do quociente de risco (QR) para estes compostos. Portanto, foi evidenciada a ocorrência de ansiolíticos e antiepilépticos no efluente do HUSM em concentrações na ordem de ng L-1. O método analítico por LC-MS/MS_Qtrap desenvolvido para a determinação das drogas psicoativas (bromazepam, carbamazepina, clonazepam, diazepam e lorazepam) no efluente hospitalar provou ser sensível, seletivo, dispensando manipulação laboriosa da amostra e exigindo corrida cromatográfica de apenas 15 minutos. A ocorrência destes fármacos e os riscos ambientais associados demonstram a necessidade de sistema mais eficiente de tratamento para o efluente hospitalar.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.