Effectiveness of Ketamine for the Treatment of Post-Traumatic Stress Disorder - A Systematic Review and Meta-Analysis.

Objective: Post-traumatic stress disorder (PTSD) is an enduring condition characterized by a chronic course and impairments across several areas. Despite its significance, treatment options remain limited, and remission rates are often low. Ketamine has demonstrated antidepressant properties and appears to be a promising agent in the management of PTSD. Method: A systematic review was conducted in PubMed/MEDLINE, Cochrane Library, Clinicaltrials.gov, Lilacs, Scopus, and Embase, covering studies published between 2012 and December 2022 to assess the effectiveness of ketamine in the treatment of PTSD. Ten studies, consisting of five RCTs, two crossover trials, and three non-randomized trials, were included in the meta-analysis. Results: Ketamine demonstrated significant improvements in PCL-5 scores, both 24 hours after the initial infusion and at the endpoint of the treatment course, which varied between 1 to 4 weeks in each study. Notably, the significance of these differences was assessed using the Two Sample T-test with pooled variance and the Two Sample Welch's T-test, revealing a statistically significant effect for ketamine solely at the endpoint of the treatment course (standardized effect size= 0.25; test power 0.9916; 95% CI = 0.57 to 17.02, p=0.0363). It is important to note that high heterogeneity was observed across all analyses. Conclusions: Our findings suggest that ketamine holds promise as an effective treatment option for PTSD. However, further trials are imperative to establish robust data for this intervention.

Cariprazine for treating psychosis: an updated meta-analysis.

PURPOSE: Early treatment of psychotic illness improves outcomes, reduces relapse rates and should not be delayed. Cariprazine is a promising antipsychotic drug and may be a valuable resource when clinicians are in doubt if psychotic symptoms are due to schizophrenia or bipolar disorder. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis that included seven studies (n = 2896) analyzing the effect of cariprazine in psychotic symptoms assessed by the positive and negative symptoms scale (PANSS). RESULTS: We found cariprazine to be significantly superior to placebo (Hedges' g = 0.40; 95% CI 0.32-0.49) for acute psychosis independently of primary psychiatric diagnosis and also to be superior to placebo for both schizophrenia (Hedges' g = 0.39; 95% CI 0.29-0.50) and bipolar patients (Hedges' g = 0.43; 95% CI 0.27-0.58). CONCLUSIONS: We propose that cariprazine may be useful in treating psychosis independently of nosological differentiation at the beginning of the treatment Key pointsEarly treatment of psychotic illness with antipsychotic medications improves outcomes and reduces relapse rates.Cariprazine was found to be significantly superior to placebo for acute psychosis independently of primary psychiatric diagnosis.Cariprazine may be useful in treating psychosis independently of nosological differentiation between schizophrenia and bipolar disorder at the beginning of the treatment.

Randomized clinical trial on the efficacy of a new transcranial direct current stimulation (tDCS) device in the treatment of depression: a low-cost option for developing countries? / Ensaio clínico randomizado sobre a eficácia de novo equipamento de estimulação transcraniana por corrente contínua (ETCC) no tratamento da depressão: uma opção de baixo custo para países em desenvolvimento?

ABSTRACT Objective: Verify the clinical efficacy and safety of a low-cost tDCS device, in a clinical trial for major depressive disorder. Methods: 168 persons were recruited; 32 depressed individuals with moderate or severe depressive symptoms (HDRS17 scores higher than 18) were included and randomized for the trial (16 individuals in each group). The intervention consisted of 10 active anodal tDCS sessions at 2 mA for 30 minutes over the left dorsolateral prefrontal cortex; or sham. The main outcome was HDRS17; secondary outcomes included satisfaction (TSQM II) and quality of life (WHOQOL-BREF). Assessments at baseline, endpoint and at 30 days follow-up. Results: The sample was composed by a total of 11 men and 21 women, mean age of 42.75 years (95% CI: 38.10-47.40). Active treatment was superior than sham: There was a significant interaction between group and time regarding HDRS-17 scores (F = 4.089, df = 2, p = 0.029; partial Eta squared = 0. 239). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms after a 30 days follow-up (difference = -7.75, p = 0.008, Cohen's d = 1.069). There were 3 dropouts, all in the active group, due schedule issues. No severe adverse effects reported. Conclusion: The current active tDCS protocol was related with clinical improvement of depressive symptoms. Intervention was well-tolerated. Non-invasive brain stimulation techniques are still not routinely used, although a viable strategy for treatment-resistant patients, partial responders and people unable to use pharmacological treatment. We aim to increase knowledge and use of tDCS for the Brazilian population.

RESUMO Objetivo: Testar a eficácia clínica e a segurança de equipamento de estimulação elétrica transcraniana por corrente contínua (ETCC) de baixo custo em ensaio clínico para transtorno depressivo maior (TDM). Métodos: Foram recrutadas 168 pessoas e incluídos e randomizados 32 indivíduos com depressão moderada ou grave (escores na HDRS17 >18; 16 indivíduos em cada grupo). A intervenção consistiu de 10 sessões de ETCC ativa a 2 mA no córtex pré-frontal dorsolateral esquerdo por 30 minutos, ou sham. O desfecho principal foi HDRS17; os desfechos secundários foram satisfação (TSQM II) e qualidade de vida (WHOQOL-BREF). Avaliações no início, no final do tratamento e após 30 dias de seguimento. Resultados: A amostra foi composta de 11 homens e 21 mulheres, com idade média de 42,75 anos (IC 95%: 38,10 a 47,40). O tratamento ativo foi superior ao sham: houve interação significativa entre grupo e tempo em relação aos escores de HDRS17 na ANOVA (F = 4,089, df = 2, p = 0,029; partial Eta squared = 0,239). A análise post hoc mostrou diferença significativa na HDRS17 no follow-up após 30 dias (diferença = -7,75, p= 0,008, Cohen's d = 1,069). Houve 3 dropouts, todos no grupo ativo, devido a problemas de agenda. Não houve registro de efeitos adversos graves. Conclusão: O tratamento ativo teve relação com melhora clínica de sintomas depressivos. A intervenção foi bem tolerada. Técnicas de estimulação cerebral não invasivas ainda não são rotina na prática clínica, apesar de estratégias viáveis para pacientes resistentes a tratamento, respondedores parciais e pessoas com intolerância a medicamentos. Esperamos ampliar o conhecimento e o uso de protocolos de ETCC na população brasileira.

Evidence for the beneficial effect of ketamine in the treatment of patients with post-traumatic stress disorder: A systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is an anxiety disorder with manifestations somatic resulting from reliving the trauma. The therapy for the treatment of PTSD has limitations, between reduced efficacy and "PTSD pharmacotherapeutic crisis". Scientific evidence has shown that the use of ketamine has benefits for the treatment of depressive disorders and other symptoms present in PTSD compared to other conventional therapies. Therefore, this study aims to analyze the available evidence on the effect of ketamine in the treatment of post-traumatic stress. The systematic review and the meta-analysis were conducted following PRISMA guidelines and RevManager software, using randomized controlled trials and eligible studies of quality criteria for data extraction and analysis. The sample design evaluated included the last ten years, whose search resulted in 594 articles. After applying the exclusion criteria, 35 articles were selected, of which 14 articles were part of the sample, however, only six articles were selected the meta-analysis. The results showed that the ketamine is a promising drug in the management of PTSD with effect more evident performed after 24 h evaluated by MADRS scale. However, the main limitations of the present review demonstrate that more high-quality studies are needed to investigate the influence of therapy, safety, and efficacy.

Longitudinal invariance of the positive and negative syndrome scale negative dimension in antipsychotic naïve first-episode schizophrenia.

AIM: Construct stability over time is required for reliable inference, but evidence regarding the longitudinal invariance of negative symptoms is still limited. Thus, we examined the longitudinal invariance of the negative dimension using the positive and negative syndrome scale (PANSS) in an antipsychotic-naïve first-episode schizophrenia sample at baseline and after 10 weeks. METHODS: Our study was conducted at a specialized early intervention service. PANSS ratings were analysed for 138 patients, and two different models were specified and tested: a unidimensional and a two-correlated factor solution. RESULTS: The unidimensional model fulfilled criteria for longitudinal invariance, whilst the two-correlated did not. CONCLUSION: Our study provides support for the PANSS negative unidimensional model use to evaluate negative symptoms' longitudinal change following first-episode schizophrenia.

Identifying strategies to improve PANSS based dimensional models in schizophrenia: Accounting for multilevel structure, Bayesian model and clinical staging.

BACKGROUND: Dimensional approaches can decompose a construct in a set of continuous variables, improving the characterization of complex phenotypes, such as schizophrenia. However, the five-factor model of the Positive and Negative Syndrome Scale (PANSS), the most used instrument in schizophrenia research, yielded poor fits in most confirmatory factor analysis (CFA) studies, raising concerns about its applications. Thus, we aimed to identify dimensional PANSS CFA models with good psychometric properties by comparing the traditional CFA with three methodological approaches: Bayesian CFA, multilevel modeling, and Multiple Indicators Multiple Causes (MIMIC) modeling. METHODS: Clinical data of 700 schizophrenia patients from four centers were analyzed. We first performed a traditional CFA. Next, we tested the three techniques: 1) a Bayesian CFA; 2) a multilevel analysis using the centers as level; and 3) a MIMIC modeling to evaluate the impact of clinical staging on PANSS factors and items. RESULTS: CFA and Bayesian CFA produced poor fit models. However, when adding a multilevel structure to the CFA model, a good fit model emerged. MIMIC modeling yielded significant differences in the factor structure between the clinical stages of schizophrenia. Sex, age, age of onset, and duration of illness did not significantly affect the model fit. CONCLUSION: Our comparison of different CFA methods highlights the need for multilevel structure to achieve a good fit model and the potential utility of staging models (rather than the duration of illness) to deal with clinical heterogeneity in schizophrenia. Large prospective samples with biological data should help to understand the interplay between psychometrics concerns and neurobiology research.

Aging biological markers in a cohort of antipsychotic-naïve first-episode psychosis patients.

Schizophrenia is a severe and multifactorial disorder with an unknown causative pathophysiology. Abnormalities in neurodevelopmental and aging processes have been reported. Relative telomere length (RTL) and DNA methylation age (DMA), well-known biomarkers for estimating biological age, are both commonly altered in patients with schizophrenia compared to healthy controls. However, few studies investigated these aging biomarkers in first-episode psychosis (FEP) and in antipsychotic-naïve patients. To cover the existing gap regarding DMA and RTL in FEP and antipsychotic treatment, we aimed to verify whether those aging markers could be associated with psychosis and treatment response. Thus, we evaluated these measures in the blood of FEP antipsychotic-naïve patients and healthy controls (HC), as well as the response to antipsychotics after 10 weeks of treatment with risperidone. RTL was measured in 392 subjects, being 80 FEP and 312 HC using qPCR, while DMA was analyzed in a subset of 60 HC, 60 FEP patients (antipsychotic-naïve) and 59 FEP-10W (after treatment) using the "Multi-tissue Predictor"and the Infinium HumanMethylation450 BeadChip Kit. We observed diminished DMA and longer RTL in FEP patients before treatment compared to healthy controls, indicating a decelerated aging process in those patients. We found no statistical difference between responder and non-responder patients at baseline for both markers. An increased DMA was observed in patients after 10 weeks of treatment, however, after adjusting for blood cell composition, no significant association remained. Our findings indicate a decelerated aging process in the early phases of the disease.

BDNF in antipsychotic naive first episode psychosis: Effects of risperidone and the immune-inflammatory response system.

Brain-derived neurotrophic factor (BDNF) and the immune-inflammatory response system (IRS) have been implicated in the pathophysiology of schizophrenia. However, no research examined the associations between BDNF and immune activation both before and after treatment in antipsychotic-naïve first episode psychosis (AN-FEP). This study aims to examine serum BDNF levels and their association with IRS and the compensatory immune-regulatory reflex system (CIRS) in AN-FEP before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed reduced levels of BDNF as compared to controls, and BDNF levels normalized after treatment with risperidone. BDNF levels were inversely correlated with a greater IRS response. Higher levels of IRS/CIRS biomarkers were associated with lower levels of BDNF including M1 macrophage, T-helper (Th)-1, Th-2, and Th-17, and T-regulatory (Treg) cell responses. Our findings indicate that AN-FEP is characterized by decreased levels of BDNF, which are normalized after treatment with risperidone. BDNF levels were inversely associated with activated immune-inflammatory pathways. The findings support the hypothesis that, increased IRS is linked to neurotoxicity, and that a decrease in BDNF may be part of the IRS/CIRS responses in FEP and, thus, be involved in the development of psychosis.

A study in first-episode psychosis patients: does angiotensin I-converting enzyme (ACE) activity associated with genotype predict symptoms severity reductions after treatment with the atypical antipsychotic risperidone?

BACKGROUND: Our previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia (SCZ) patients compared to healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting SCZ was suggested. METHODS: ACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (N = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (N = 45), assessed at baseline (FEB-B) and also after 2-months (FEP-2M) of treatment with the atypical antipsychotic risperidone. RESULTS: ACE activity measurements showed significant differences among HC, FEP-B and FEP-2M groups (F = 5.356, df = 2, p = 0.005), as well as between HC and FEP-2M (post-hoc Tukey's multiple comparisons test, p = 0.004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total PANSS (r = -0.131, p = 0.434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, p = 0.392), but ACE activity levels differences observed between these groups were influenced by age. CONCLUSIONS: The importance of measuring the ACE activity in blood plasma, associated to ACE I/D genotyping to support the follow-up of FEP patients did not show correlation with general symptoms amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated.

LINE-1 hypomethylation is associated with poor risperidone response in a first episode of psychosis cohort.

Aim: We investigated the DNA methylation profile over LINE-1 in antipsychotic-naive, first-episode psychosis-patients (n = 69) before and after 2 months of risperidone treatment and in healthy controls (n = 62). Materials & methods: Patients were evaluated using standardized scales and classified as responders and nonresponders. DNA from blood was bisulfite converted and LINE-1 fragments were amplified and pyrosequencing was performed. Results: Lower LINE-1 methylation was observed in antipsychotic-naive first-episode psychosis patients than in healthy controls. Lower DNA methylation levels before treatment were associated with poor risperidone responses. A positive correlation was observed between LINE-1 methylation levels and positive symptoms response. Conclusion: Our study brings new insight regarding how epigenomic studies and clinical correlation studies can supplement psychosis treatment.

Family members affected by multiple substance misuse relatives. / Familiares afectados por el abuso de sustancias de otros parientes: características de una muestra brasileña.

PURPOSE: The heterogenic characteristics of affected family members (AFMs) of substance misusing relative (SMR) remain understudied. This study examined the occurrence and correlates of AFMs having more than one relative with substance use problems. MATERIAL AND METHODS: A secondary analysis of a cross-sectional study on the characteristics of affected family members in Brazil was performed (N= 3157). Levels of AFM stress, strain, coping and hopefulness were assessed. Factors associated with AFMs having other substance misusing relatives (other-SMRs) were explored using univariate logistic regressions. RESULTS: The occurrence of having other-SMR was reported by 61.6% of the sample (1945/3157). Of this, 47% (904/1945) reported that the other-SMR was a member of the SMR's immediate family (spouse/partner/children/siblings). The likelihood of having other-SMRs was related to the AFM being female, from a low socioeconomic background, between the age of 35-44 years older, being SMR's mother or wife/girlfriend/fiancée, scoring higher on family member impact, psychological and physical symptoms, withdrawal coping and to have an older SMR. CONCLUSION: Information about the characteristics of AFMs is key to understanding how the experience of harm associated with the relative's problem might manifest. Our findings offer information that could be used when developing interventions aimed at reducing the harm experienced by AFMs.

Objetivo: Las características heterogéneas de familiares afectados (FA) de familiares con abuso de sustancias (FAS) han sido objeto de pocos estudios. Este estudio revisó la ocurrencia y los correlatos de FA con uno o más familiares con problemas de abuso de sustancias. Materiales y Métodos: Análisis secundario de un estudio transversal sobre las características de FA en Brasil (N = 3157). Valoramos los niveles de los FA de estrés, presión, afrontamiento y esperanza. Exploramos los factores asociados con los FA que tenían otros familiares con abuso de sustancias (otros-FAS) mediante regresiones logísticas ordinales. Resultados: El 61,6% de la muestra (1945/3157) informó de la ocurrencia de otros-FAS. De estos, el 47% (904/1945) informó que los otros-FAS eran familiares directos del FAS (cónyuge/pareja/hijos/hermanos). La probabilidad de ocurrencia de otros-FAS estaba relacionada con que el FAS fuese mujer, de bajo nivel socioeconómico (NSE), con una edad entre los 35-44 años, fuese la madre o esposa/novia/prometida del FAS, obtuviese una puntuación más alta en impacto familiar, síntomas psicológicos y físicos, evitamiento como mecanismo de afrontamiento, y que tuviese un FAS mayor. Conclusión: Información sobre las características de los FA es clave para entender cómo puede manifestarse la experiencia de daños asociados con el problema del familiar. Nuestros hallazgos aportan datos que pueden ser útiles para desarrollar intervenciones con el objetivo de reducir los daños sufridos por los FA.

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.

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.

Impact of duration of untreated psychosis in short-term response to treatment and outcome in antipsychotic naïve first-episode psychosis.

AIM: Duration of untreated psychosis (DUP) is one of the few potentially modifiable outcome predictors in psychosis. Previous studies have associated a longer DUP with a poor prognosis, but few of them were performed in countries with low and middle level of income. This study aimed to investigate the DUP in a Brazilian sample of antipsychotic-naïve first-episode psychosis (AN-FEP) patients and its association with clinical characteristics and treatment outcomes in a short-term follow-up. METHODS: One hundred forty-five AN-FEP patients between 16 and 40 years were enrolled and were reassessed 10 weeks after risperidone treatment. We investigated the association between DUP and symptom severity, functionality and response to treatment, using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI) and the Global Assessment of Functionality (GAF) scale. DUP was defined as the period between the onset of the first psychotic symptoms and the first effective antipsychotic treatment. For the analysis, we performed multivariate linear regressions. RESULTS: The DUP's median was 61 days. At baseline, we did not find any significant association between DUP and clinical characteristics. After treatment, the longer DUP predicted worse positive and negative symptom dimensions, worse total PANSS, GAF and CGI scores and poorer response to treatment. CONCLUSION: Our results showed that DUP is associated with worse outcomes after short treatment, but it does not modify the baseline clinical profile of the AN-FEP patients. Such results reinforce the need to develop early intervention strategies, reducing DUP.

Predictors of Disagreement Between Diagnoses From Consult Requesters and Consultation-Liaison Psychiatry.

We evaluated disagreement between reported symptoms and a final diagnosis of depression, anxiety, withdrawal, psychosis, or delirium through regression models assessing individual and combined diagnoses. Highest disagreement rates were reported for services classified as others (88.2%), general surgery (78.5%), and bone marrow transplant (77.7%). Disagreement rates varied widely across different diagnoses, with anxiety having the highest disagreement rate (63.3%), whereas psychosis had the lowest disagreement rate (10.6%). When evaluating kappa coefficients, the highest agreement occurred with diagnoses of withdrawal and psychosis (0.66% and 0.51%, respectively), whereas anxiety and depression presented the lowest values (0.31% and 0.11%, respectively). The best-performing predictive model for most outcomes was random forest, with the most important predictors being specialties other than the ones focused on single systems, older age, lack of social support, and the requester being a resident. Monitoring disagreement rates and their predictors provides information that could lead to quality improvement and safety programs.

Peripheral biomarkers allow differential diagnosis between schizophrenia and bipolar disorder.

Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders that pose important challenges for diagnosis by sharing common symptoms, such as delusions and hallucinations. The underlying pathophysiology of both disorders remains largely unknown, and the identification of biomarkers with potential to support diagnosis is highly desirable. In a previous study, we successfully discriminated SCZ and BD patients from healthy control (HC) individuals by employing proton magnetic resonance spectroscopy (1H-NMR). In this study, 1H-NMR data treated by chemometrics, principal component analysis (PCA) and supervised partial least-squares discriminant analysis (PLS-DA), provided the identification of metabolites present only in BD (as for instance the 2,3-diphospho-D-glyceric acid, N-acetyl aspartyl-glutamic acid, monoethyl malonate) or only in SCZ (as isovaleryl carnitine, pantothenate, mannitol, glycine, GABA). This may represent a set of potential biomarkers to support the diagnosis of these mental disorders, enabling the discrimination between SCZ and BD, and among these psychiatric patients and HC (as 6-hydroxydopamine was present in BD and SCZ but not in HC). The presence or absence of these metabolites in blood allowed the categorization of 182 independent subjects into one of these three groups. In addition, the presented data suggest disturbances in metabolic pathways in SCZ and BD, which may provide new and important information to support the elucidation and/or new insights into the neurobiology underlying these mental disorders.

Forensic Implications of the New Classification of ICD-11 Paraphilic Disorders in Brazil.

INTRODUCTION: The World Health Organization (WHO) Department of Mental Health and Substance Abuse appointed a Working Group on Sexual Disorders and Sexual Health in order to revise and propose changes to ICD-10 categories. AIM: Analyze ethical and legal implications in Brazil of the proposed ICD-11 diagnostic criteria for paraphilic disorders. METHODS: A forensic working group of Brazilian experts in collaboration with representatives of WHO reviewed the proposed modifications to the classification of Disorders of Sexual Preference in ICD-10 (F65), which is recommended to be replaced by Paraphilic Disorders in ICD-11. Proposals were reviewed through a medicolegal lens, using a legal and policy analysis guide put forth by WHO. The premise of this review was to understand that, although the ICD classification is intended to provide a basis for clinical and statistical health interventions, medical diagnostics may also be entangled in the complex legal, normative, and political environment of various countries. MAIN OUTCOME MEASURE: The most important proposed change to this section is to limit the concept of paraphilic disorders primarily to patterns of sexual arousal involving a focus on others who are unwilling or unable to consent, but this change has not affected the ethical and legal aspects of psychiatric functioning in the Brazil. RESULTS: Because Brazilian criminal law is directed toward criminal behavior and not to specific psychiatric diagnoses, the changes proposed for ICD-11 are not expected to create obstacles to health services or to modify criminal sentencing. CLINICAL IMPLICATIONS: Although ICD-11 has a number of changes in its content, there are no significant clinical implications in the Brazilian context, but a better clarity of conceptual definitions and diagnostic criteria. STRENGTHS & LIMITATIONS: The study is conducted with people from different Brazilian states, which is important for a comprehensive view. On the other hand, considering that it is a very heterogeneous country, there is the limitation that an even wider scope of the study is not possible. CONCLUSION: In the Brazilian context, the new guidelines for paraphilic disorders contribute to clinical utility and are not expected to create difficulties related to the legal, social, and economic consequences of sexual offenses in the country. Abdalla-Filho E, de Jesus Mari J, Diehl A, et al. Forensic Implications of the New Classification of ICD-11 Paraphilic Disorders in Brazil. J Sex Med 2019; 16:1814-1819.

Brazilian guidelines for the management of psychomotor agitation. Part 2. Pharmacological approach

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.

Adulterants in crack cocaine in Brazil.

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.