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[PMID]: 28768940 [Au] Autor: Inomata A; Ogata A; Tada Y; Nagasawa A; Yuzawa K; Ando H; Kubo Y; Takahashi H; Kaihoko F; Tanaka K; Nakajima J; Suzuki A; Uemura N; Moriyasu T; Watanabe D; Ishihara K; Usami T; Kamei S; Kohno Y [Ad] Endereço: Tokyo Metropolitan Institute of Public Health. [Ti] Título: Inhalation Exposure Method for Illegal Drugs. [So] Source: Yakugaku Zasshi;137(8):1005-1015, 2017. [Is] ISSN: 1347-5231 [Cp] País de publicação: Japan [La] Idioma: jpn [Ab] Resumo: We developed a new inhalation exposure method to evaluate effects of synthetic cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo area. We selected the commercial product "SOUTOU" containing AB-CHMINACA and 5F-AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU was ignited, then mainstream smoke from each was delivered to five mice in an exposure box. After the cigarettes were fully consumed, neurobehavioral observations and a catalepsy test were performed at 15, 30 and 60 min after exposure. The effluent air from the exposure box was poured into impingers containing acetonitrile (first impinger) and dimethyl sulfoxide (second impinger). The resulting solutions were analyzed to assess decomposition of the synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly included cannabimimetic specific pharmacological actions. Negative control mice also showed some suppressive behaviors at 15 min but these were attenuated at later times, nearly disappearing at 60 min. In addition, the behavioral effects observed in controls were less pronounced than those in SOUTOU exposed mice. The inhalation exposure method developed in our study would be effective for determining cannabinoid specific pharmacological effects of illegal drugs, as well as for assessing the presence of active compound(s) by comparing the test substance with a negative control. [Mh] Termos MeSH primário: Câmaras de Exposição Atmosférica Comportamento Animal/efeitos dos fármacos Canabinoides/efeitos adversos Exposição por Inalação/efeitos adversos Drogas Ilícitas/efeitos adversos [Mh] Termos MeSH secundário: Acatisia Induzida por Medicamentos Althaea Animais Canabinoides/química Masculino Camundongos Endogâmicos ICR Folhas de Planta Fatores de Tempo Produtos do Tabaco [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cannabinoids); 0 (Street Drugs) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171030 [Lr] Data última revisão: 171030 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170804 [St] Status: MEDLINE [do] DOI: 10.1248/yakushi.17-00019

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[PMID]: 28579487 [Au] Autor: Miró Ò; Galicia M; Dargan P; Dines AM; Giraudon I; Heyerdahl F; Hovda KE; Yates C; Wood DM; Euro-DEN Research Group [Ad] Endereço: Emergency Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain. [Ti] Título: Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse. [So] Source: Toxicol Lett;277:84-91, 2017 Aug 05. [Is] ISSN: 1879-3169 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse. METHOD: We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes. RESULTS: We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment (59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12h, p<0.01). CONCLUSIONS: The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse. [Mh] Termos MeSH primário: 4-Butirolactona/envenenamento Overdose de Drogas Oxibato de Sódio/envenenamento Drogas Ilícitas/envenenamento Transtornos Relacionados ao Uso de Substâncias [Mh] Termos MeSH secundário: Adulto Acatisia Induzida por Medicamentos/etiologia Acatisia Induzida por Medicamentos/fisiopatologia Acatisia Induzida por Medicamentos/psicologia Estado de Consciência/efeitos dos fármacos Interações Medicamentosas Overdose de Drogas/diagnóstico Overdose de Drogas/fisiopatologia Overdose de Drogas/psicologia Overdose de Drogas/terapia Serviço Hospitalar de Emergência Europa (Continente) Feminino Seres Humanos Intubação Intratraqueal Masculino Atividade Motora/efeitos dos fármacos Estudos Prospectivos Respiração Artificial Índice de Gravidade de Doença Oxibato de Sódio/análogos & derivados Transtornos Relacionados ao Uso de Substâncias/diagnóstico Transtornos Relacionados ao Uso de Substâncias/fisiopatologia Transtornos Relacionados ao Uso de Substâncias/psicologia Transtornos Relacionados ao Uso de Substâncias/terapia Fatores de Tempo Resultado do Tratamento [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY [Nm] Nome de substância: 0 (Street Drugs); 7G33012534 (Sodium Oxybate); OL659KIY4X (4-Butyrolactone) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170807 [Lr] Data última revisão: 170807 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170606 [St] Status: MEDLINE

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[PMID]: 28343051 [Au] Autor: Earley W; Durgam S; Lu K; Debelle M; Laszlovszky I; Vieta E; Yatham LN [Ad] Endereço: Allergan, Jersey City, NJ, USA. Electronic address: Willie.Earley@Allergan.com. [Ti] Título: Tolerability of cariprazine in the treatment of acute bipolar I mania: A pooled post hoc analysis of 3 phase II/III studies. [So] Source: J Affect Disord;215:205-212, 2017 Jun. [Is] ISSN: 1573-2517 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: BACKGROUND: Atypical antipsychotics have broad-spectrum efficacy against core symptoms of acute mania/mixed states in bipolar disorder; however, they are associated with clinically significant adverse effects (AEs). METHODS: This post hoc analysis evaluated the safety and tolerability of the atypical antipsychotic cariprazine in the treatment of adult patients with acute manic/mixed episodes of bipolar I disorder. Data were taken from three 3-week randomized, double-blind, placebo-controlled, flexible-dose trials of cariprazine 3-12mg/d. Patient subgroups categorized by modal daily dose (3-6mg/d; 9-12mg/d) were used to assess dose response. RESULTS: The pooled safety population comprised 1065 patients (placebo=442; cariprazine 3-6mg/d=263; cariprazine 9-12mg/d=360). More cariprazine- than placebo-treated patients reported double-blind treatment-emergent AEs; the overall AE incidence was similar among cariprazine-dose groups. AEs reported in ≥5% of cariprazine patients overall with at least twice the incidence of placebo were akathisia, extrapyramidal symptoms, restlessness, and vomiting. The incidence of SAEs was low and similar between the placebo- and cariprazine-treatment groups. Metabolic parameter changes were small and generally similar between cariprazine and placebo groups; mean increases in fasting glucose levels were greater with cariprazine (3-6mg/d=6.6mg/dL; 9-12mg/d=7.2mg/dL) than placebo (1.7mg/dL). Mean weight change was 0.54kg and 0.17kg for cariprazine and placebo, respectively; weight increase ≥7% was <3% in all treatment groups. Cariprazine was not associated with clinically meaningful changes in electrocardiogram parameters. LIMITATIONS: Post hoc analysis, flexible-dose design, short trial duration. CONCLUSION: Cariprazine was generally safe and well-tolerated in patients with manic/mixed episodes associated with bipolar I disorder. [Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico Transtorno Bipolar/tratamento farmacológico Piperazinas/uso terapêutico [Mh] Termos MeSH secundário: Adulto Acatisia Induzida por Medicamentos/etiologia Antipsicóticos/efeitos adversos Feminino Seres Humanos Masculino Meia-Idade Piperazinas/efeitos adversos Ensaios Clínicos Controlados Aleatórios como Assunto [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antipsychotic Agents); 0 (Piperazines); F6RJL8B278 (cariprazine) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170619 [Lr] Data última revisão: 170619 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170327 [St] Status: MEDLINE

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[PMID]: 28246265 [Au] Autor: Maund E; Guski LS; Gøtzsche PC [Ad] Endereço: Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark em@cochrane.dk. [Ti] Título: Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports. [So] Source: CMAJ;189(5):E194-E203, 2017 Feb 06. [Is] ISSN: 1488-2329 [Cp] País de publicação: Canada [La] Idioma: eng [Ab] Resumo: BACKGROUND: The European Medicines Agency makes clinical study reports publicly available and publishes reasons for not approving applications for marketing authorization. Duloxetine has been approved in Europe for the treatment of stress urinary incontinence in women. The reported adverse effects of duloxetine include mental health problems and suicidality. We obtained clinical study reports from the European Medicines Agency concerning use of this drug for stress urinary incontinence. METHODS: We performed a meta-analysis of 4 randomized placebo-controlled trials of duloxetine (involving a total of 1913 patients) submitted to the European Medicines Agency for marketing approval for the indication of stress urinary incontinence in women. We used data from the clinical study reports (totalling 6870 pages and including individual patient data) to assess benefits (including frequency of incontinence and changes in quality-of-life scores, such as Patient Global Impression of Improvement rating) and harms (both general harms, including discontinuation because of adverse events, and harms related to suicidality, violent behaviour and their potential precursors, such as akathisia and activation [stimulating effects such as insomnia, anxiety and agitation]). RESULTS: Duloxetine was significantly better than placebo in terms of percentage change in weekly incontinence episodes (mean difference -13.56%, 95% confidence interval [CI] -21.59% to -5.53%) and change in Incontinence Quality of Life total score (mean difference 3.24, 95% CI 2.00 to 4.48). However, the effect sizes were small, and a sensitivity analysis (with removal of one trial) showed that the number needed to treat for a Patient Global Impression of Improvement rating of "much better or very much better" was 8 (95% CI 6 to 13). The numbers needed to harm were 7 (95% CI 6 to 8) for discontinuing because of an adverse event and 7 (95% CI 6 to 9) for experiencing an activation event. No suicidality, violence or akathisia events were noted. INTERPRETATION: Although duloxetine is effective for stress urinary incontinence in women, the rates of associated harm were high when individual patient data were analyzed, and the harms outweighed the benefits. [Mh] Termos MeSH primário: Antidepressivos/uso terapêutico Cloridrato de Duloxetina/uso terapêutico Incontinência Urinária por Estresse/tratamento farmacológico [Mh] Termos MeSH secundário: Sintomas Afetivos/induzido quimicamente Acatisia Induzida por Medicamentos/etiologia Ansiedade/induzido quimicamente Feminino Seres Humanos Transtornos Mentais/induzido quimicamente Psicoses Induzidas por Substâncias/etiologia Ensaios Clínicos Controlados Aleatórios como Assunto Medição de Risco Distúrbios do Início e da Manutenção do Sono/induzido quimicamente Ideação Suicida Resultado do Tratamento Violência [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS [Nm] Nome de substância: 0 (Antidepressive Agents); 9044SC542W (Duloxetine Hydrochloride) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 171010 [Lr] Data última revisão: 171010 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170302 [St] Status: MEDLINE [do] DOI: 10.1503/cmaj.151104

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[PMID]: 28141623 [Au] Autor: Citrome L [Ad] Endereço: From the Department of Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, NY. [Ti] Título: Activating and Sedating Adverse Effects of Second-Generation Antipsychotics in the Treatment of Schizophrenia and Major Depressive Disorder: Absolute Risk Increase and Number Needed to Harm. [So] Source: J Clin Psychopharmacol;37(2):138-147, 2017 Apr. [Is] ISSN: 1533-712X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: PURPOSE/BACKGROUND: Activating and sedating adverse effects of antipsychotics can be obstacles to their use. METHODS/PROCEDURES: This study quantified the activating and sedating properties of first-line oral second-generation antipsychotics by examining the rates of adverse reactions as reported in product labeling for the indications of schizophrenia and adjunctive treatment of major depressive disorder. Additional data sources included regulatory documents, study synopses, and published study reports. Attributable risk increase and number needed to harm (NNH) were calculated for each agent versus placebo. FINDINGS/RESULTS: Heterogeneity among the different antipsychotics regarding activating or sedating adverse events was observed, with some agents displaying the potential for both activating and sedating properties. For agents indicated for the treatment of schizophrenia, predominantly activating medications include lurasidone (NNH, 11 for akathisia vs 20 for somnolence) and cariprazine (NNH, 15 for akathisia vs 65 for somnolence-combined terms). Similarly activating and sedating are risperidone (NNH, 15 for akathisia vs 13 for sedation) and aripiprazole (NNH, 31 for akathisia vs 34 for somnolence). Predominantly sedating are olanzapine, quetiapine immediate and extended release, ziprasidone, asenapine, and iloperidone. Agents that are neither activating nor sedating are paliperidone and brexpiprazole. For major depressive disorder, the overall findings regarding activation and sedation appear similar to those seen with schizophrenia. Data extracted were limited to those available from registrational studies that contributed to the adverse event tables contained in the product labels. Postregistrational comparative studies may yield different outcomes. IMPLICATIONS/CONCLUSIONS: Differences in tolerability profiles regarding activation and sedation have implications in terms of selecting the optimal antipsychotic for a given individual. [Mh] Termos MeSH primário: Acatisia Induzida por Medicamentos/epidemiologia Antipsicóticos/efeitos adversos Sedação Consciente/estatística & dados numéricos Transtorno Depressivo Maior/tratamento farmacológico Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia Fadiga/epidemiologia Esquizofrenia/tratamento farmacológico [Mh] Termos MeSH secundário: Antipsicóticos/farmacologia Distúrbios do Sono por Sonolência Excessiva/epidemiologia Seres Humanos Agitação Psicomotora/epidemiologia Distúrbios do Início e da Manutenção do Sono/epidemiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS [Nm] Nome de substância: 0 (Antipsychotic Agents) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170626 [Lr] Data última revisão: 170626 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170201 [St] Status: MEDLINE [do] DOI: 10.1097/JCP.0000000000000665

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[PMID]: 28141621 [Au] Autor: Mentzel TQ; Lieverse R; Bloemen O; Viechtbauer W; van Harten PN; Genetic Risk and Outcome of Psychosis (GROUP) Investigators [Ad] Endereço: From the *Innova, GGZ Centraal, Amersfoort; and †Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. [Ti] Título: High Incidence and Prevalence of Drug-Related Movement Disorders in Young Patients With Psychotic Disorders. [So] Source: J Clin Psychopharmacol;37(2):231-238, 2017 Apr. [Is] ISSN: 1533-712X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Drug-related movement disorders (DRMDs) reduce quality of life and contribute to medication noncompliance of patients with psychotic disorders. Little is known about the epidemiology of DRMDs in relatively young patients a few years after onset of psychosis. This is an important period to study, as the impact of the antipsychotic treatment on the long-term potentiation of the neural pathways associated with psychotic disorders and DRMDs is still minimal. This study investigated the prevalence, incidence, persistence, and clinical correlates of DRMDs in patients during their first years after disease onset. METHODS: The Genetic Risk and Outcome of Psychosis study is a longitudinal study of 1120 relatively young patients with nonaffective psychosis and a mean age and illness duration of 27 and 4 years, respectively. The following drug-related movement disorders were assessed at baseline and at the 3-year follow-up: parkinsonism, akathisia, tardive dyskinesia, and tardive dystonia. We determined prevalence, incidence, and persistence and investigated clinical correlates at and over the baseline and follow-up assessment. RESULTS: Patients' mean age and illness duration at baseline were 27.1 and 4.3 years, respectively. In 4 patients, 1 developed a DRMD over the 3-year study period. Prevalence, incidence, and persistence rates were highest for parkinsonism (32%, 21%, and 53%) followed by akathisia (9%, 5%, and 17%) and tardive dyskinesia (4%, 3%, and 20%). Significant associations were found between DRMDs and the patients' age, IQ, and psychopathology. CONCLUSIONS: The prevalence, persistence, and incidence of DRMDs in this sample were high despite the relatively young age, recent onset of the disorder, and treatment primarily with second-generation antipsychotics. These findings emphasize that screening, diagnosis, and treatment of DRMDs are still important. [Mh] Termos MeSH primário: Acatisia Induzida por Medicamentos/etiologia Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia Distonia/induzido quimicamente Doença de Parkinson Secundária/induzido quimicamente Transtornos Psicóticos/tratamento farmacológico Discinesia Tardia/induzido quimicamente [Mh] Termos MeSH secundário: Adolescente Adulto Acatisia Induzida por Medicamentos/epidemiologia Bélgica/epidemiologia Distonia/epidemiologia Feminino Seres Humanos Incidência Estudos Longitudinais Masculino Meia-Idade Países Baixos/epidemiologia Doença de Parkinson Secundária/epidemiologia Prevalência Transtornos Psicóticos/epidemiologia Discinesia Tardia/epidemiologia Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170626 [Lr] Data última revisão: 170626 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170201 [St] Status: MEDLINE [do] DOI: 10.1097/JCP.0000000000000666

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[PMID]: 28117179 [Au] Autor: Bounes V; Charriton-Dadone B; Levraut J; Delangue C; Carpentier F; Mary-Chalon S; Houze-Cerfon V; Sommet A; Houze-Cerfon CH; Ganetsky M [Ad] Endereço: Pôle Médecine d'Urgence, Hôpital Universitaire de Purpan, Toulouse 31059 Cedex 9, France; INSERM UMR 1027, Université Paul Sabatier, Toulouse 31000, France. Electronic address: bounes.v@chu-toulouse.fr. [Ti] Título: Predicting morphine related side effects in the ED: An international cohort study. [So] Source: Am J Emerg Med;35(4):531-535, 2017 Apr. [Is] ISSN: 1532-8171 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: STUDY OBJECTIVES: Morphine is the reference treatment for severe acute pain in an emergency department. The purpose of this study was to describe and analyse opioid-related ADRs (adverse drug reactions) in a large cohort of emergency department patients, and to identify predictive factors for those ADRs. METHODS: In this prospective, observational, pharmaco-epidemiological international cohort study, all patients aged 18years or older who were treated with morphine were enrolled. The study was done in 23 emergency departments in the US and France. Baseline numerical rating scale score and initial and total doses of morphine titration were recorded. Logistic regression analysis was used to study the effects of demographic, clinical and medical history covariates on the occurrence of opioid-induced ADRs within 6h after treatment. RESULTS: A total of 1128 patients were included over 10months. Median baseline initial pain scores were 8/10 (7-10) versus 3/10 (1-4) after morphine administration. Median titration duration was 10min (IQR, 1-30). The occurrence of opioid-induced ADRs was 25% and 2% were serious. Patients experienced mainly nausea and drowsiness. Medical history of travel sickness (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.01-2.86) and history of nausea or vomiting post morphine (OR, 3.86; 95% CI, 2.29-6.51) were independent predictors of morphine related ADRs. CONCLUSION: Serious morphine related ADRs are rare and unpredictable. Prophylactic antiemetic therapy could be proposed to patients with history of travel sickness and history of nausea or vomiting in a postoperative setting or after morphine administration. [Mh] Termos MeSH primário: Dor Aguda/tratamento farmacológico Acatisia Induzida por Medicamentos/etiologia Analgésicos Opioides/efeitos adversos Morfina/efeitos adversos Náusea/induzido quimicamente Prurido/induzido quimicamente Vômito/induzido quimicamente [Mh] Termos MeSH secundário: Adulto Idoso Acatisia Induzida por Medicamentos/epidemiologia Estudos de Coortes Serviço Hospitalar de Emergência Feminino França/epidemiologia Seres Humanos Modelos Logísticos Masculino Meia-Idade Enjoo devido ao Movimento/epidemiologia Análise Multivariada Náusea/epidemiologia Razão de Chances Farmacoepidemiologia Estudos Prospectivos Prurido/epidemiologia Fatores de Risco Fases do Sono Estados Unidos/epidemiologia Vômito/epidemiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY [Nm] Nome de substância: 0 (Analgesics, Opioid); 76I7G6D29C (Morphine) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170417 [Lr] Data última revisão: 170417 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170125 [St] Status: MEDLINE

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[PMID]: 28079463 [Au] Autor: Ozbey G; Celikel FC; Cumurcu BE; Kan D; Yucel B; Hasbek E; Percin F; Guzey IC; Uluoglu C [Ad] Endereço: a Department of Pharmacology , Akdeniz University Medical Faculty , Antalya , Turkey. [Ti] Título: Influence of ABCB1 polymorphisms and serum concentrations on venlafaxine response in patients with major depressive disorder. [So] Source: Nord J Psychiatry;71(3):230-237, 2017 Apr. [Is] ISSN: 1502-4725 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: The pharmacokinetics and the pharmacodynamics of antidepressants show large inter-individual variations which result in unpredictable clinical responses. AIM: The aim of the study was to examine the effect of ABCB1 polymorphisms and the serum concentrations on the efficacy and tolerability of venlafaxine in patients with major depressive disorder (MDD). METHODS: Fifty-two outpatients who met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for MDD were recruited for the study. The severity of depression was assessed using the 17-item Hamilton Rating Scale for Depression scale (HDRS ) and tolerability was assessed based on a query regarding side-effects for 6 weeks. The ABCB1 C3435T/A and G2677T/A polymorphisms were genotyped by PCR/RFLP and steady-state serum venlafaxine concentrations were measured by high-performance liquid chromatography. RESULTS: Patients with the TT genotype for the C3435T and the TT/TA genotype for the G2677T/A polymorphism showed significantly higher frequencies in venlafaxine-induced akathisia. This relationship was not observed for efficacy. As regards serum venlafaxine concentrations, patient groups showed no significant differences in efficacy and tolerability. CONCLUSION: The results suggest that individuals with the TT-TT/TA genotypes for the C3435T-G2677T/A polymorphisms of ABCB1 may be pre-disposed to a risk of akathisia. [Mh] Termos MeSH primário: Acatisia Induzida por Medicamentos/genética Transtorno Depressivo Maior/tratamento farmacológico Transtorno Depressivo Maior/genética Inibidores da Recaptação de Serotonina e Norepinefrina/sangue Cloridrato de Venlafaxina/sangue [Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/genética Adulto Idoso Feminino Seres Humanos Masculino Meia-Idade Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos Cloridrato de Venlafaxina/administração & dosagem Cloridrato de Venlafaxina/efeitos adversos Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (Serotonin and Noradrenaline Reuptake Inhibitors); 7D7RX5A8MO (Venlafaxine Hydrochloride) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170113 [St] Status: MEDLINE [do] DOI: 10.1080/08039488.2016.1268203

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[PMID]: 28075189 [Au] Autor: Roberts L; Ford L; Patel N; Vale JA; Bradberry SM [Ad] Endereço: a West Midlands Poisons Unit , City Hospital , Birmingham , UK. [Ti] Título: 11 analytically confirmed cases of mexedrone use among polydrug users. [So] Source: Clin Toxicol (Phila);55(3):181-186, 2017 Mar. [Is] ISSN: 1556-9519 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Mexedrone, 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one, is the alpha-methoxy-derivative of mephedrone (4-methyl-N-methyl cathinone). Mexedrone inhibits the re-uptake of serotonin and dopamine in a dose-dependent manner and has affinity for serotonin and dopamine membrane transporters and receptors (5-HT2 and D2 receptors), producing sympathomimetic effects similar to amfetamines. To date there are no published clinical reports on mexedrone use that are analytically confirmed. OBJECTIVE: To characterise the features of mexedrone use in patients who presented to our hospital after using a variety of psychoactive substances including mexedrone, with analytical confirmation in each case. METHODS: This is an observational case series. Urine toxicological screening using ultra-performance liquid chromatography with tandem mass spectrometry and exact mass time of flight was employed in all patients. RESULTS: A total of 305 cases were screened and mexedrone was identified in 11 urine samples. Agitation was the most common presenting feature in 10 of 11 patients. This was marked to the extent of aggression in some cases, with six patients requiring sedation and/or physical restraint. Delusions and hallucinations, often with paranoia, were observed in three cases with a prominent supernatural/demonic theme. None of these individuals had a history of psychosis. Seven of 11 patients were tachycardic >100 bpm. The median length of stay was 20 hours (range 2-77; IQR 4-33). Mexedrone alone is only likely to have been responsible for these clinical features in 2 cases; in two others mexedrone was found in high concentration along with substantial amounts of other stimulants. In 7 other cases other stimulants detected more likely explained the features. However, comprehensive analytical data enabled us to identify the full complement of agents contributing to the clinical presentation. CONCLUSIONS: Agitation was the predominant clinical feature in this case series and was often accompanied by a sinus tachycardia; mexedrone was primarily responsible in 2 patients but contributed substantially in two others. Patients typically recovered fully within 24 hours, unless they required sedation. [Mh] Termos MeSH primário: Drogas Desenhadas/toxicidade Metanfetamina/análogos & derivados Drogas Ilícitas/toxicidade Detecção do Abuso de Substâncias/métodos Transtornos Relacionados ao Uso de Substâncias/diagnóstico [Mh] Termos MeSH secundário: Adulto Acatisia Induzida por Medicamentos/epidemiologia Acatisia Induzida por Medicamentos/etiologia Cromatografia Líquida de Alta Pressão/métodos Seres Humanos Tempo de Internação Metanfetamina/toxicidade Metanfetamina/urina Meia-Idade Drogas Ilícitas/urina Taquicardia Sinusal/induzido quimicamente Taquicardia Sinusal/epidemiologia Espectrometria de Massas em Tandem/métodos Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; OBSERVATIONAL STUDY [Nm] Nome de substância: 0 (Designer Drugs); 0 (Street Drugs); 0 (mexedrone); 44RAL3456C (Methamphetamine) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170817 [Lr] Data última revisão: 170817 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170112 [St] Status: MEDLINE [do] DOI: 10.1080/15563650.2016.1271424

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[PMID]: 28027109 [Au] Autor: Rasmussen SA; Rosebush PI; Mazurek MF [Ad] Endereço: From the Departments of *Medicine, †Psychiatry & Behavioural Neurosciences, and ‡Medicine (Neurology), McMaster University, Hamilton, Ontario, Canada. [Ti] Título: The Relationship Between Early Haloperidol Response and Associated Extrapyramidal Side Effects. [So] Source: J Clin Psychopharmacol;37(1):8-12, 2017 Feb. [Is] ISSN: 1533-712X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Early response to antipsychotic medication within 2 weeks of initiating treatment can predict psychiatric outcomes. However, it is unclear whether early response is also predictive of extrapyramidal side effects (EPSs) associated with antipsychotic medications. METHODS: In this study, we investigated 136 consecutive antipsychotic-naive, first-episode psychosis patients naturalistically treated with haloperidol. Patients were assessed at baseline and weekly after treatment initiation using the Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. Dystonia, parkinsonism, akathisia, and dyskinesia were also assessed weekly using standardized rating scales. Regression analyses were used to determine whether early response at week 2 of treatment predicted the incidence of EPS at any point during hospitalization. A secondary analysis was conducted to determine whether early response continued to predict EPS in patients who experienced no EPS within the first 2 weeks of treatment. RESULTS: The analyses demonstrated that greater Brief Psychiatric Rating Scale percent improvement at week 2 predicted a decreased risk of EPSs (P = 0.004), even in patients who did not show any EPSs within the first 2 weeks of treatment (P = 0.005). For specific EPS, early response predicted decreased incidences of parkinsonism (P = 0.028) and dyskinesia (P = 0.025), but not akathisia or dystonia. Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale improvement at week 2 did not predict EPSs. In addition, EPSs were not predicted by the maximum antipsychotic dose received during hospitalization. CONCLUSIONS: These results indicate that early antipsychotic response is valuable not only for predicting psychiatric outcomes, but also for predicting the risk of EPSs. [Mh] Termos MeSH primário: Acatisia Induzida por Medicamentos/etiologia Antipsicóticos/farmacologia Discinesia Induzida por Medicamentos/etiologia Distonia/induzido quimicamente Haloperidol/farmacologia Avaliação de Resultados (Cuidados de Saúde) Transtornos Psicóticos/tratamento farmacológico [Mh] Termos MeSH secundário: Adulto Antipsicóticos/efeitos adversos Escalas de Graduação Psiquiátrica Breve Feminino Haloperidol/efeitos adversos Seres Humanos Masculino Meia-Idade Prognóstico Risco Fatores de Tempo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antipsychotic Agents); J6292F8L3D (Haloperidol) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170510 [Lr] Data última revisão: 170510 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161228 [St] Status: MEDLINE [do] DOI: 10.1097/JCP.0000000000000637

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