Objective: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an antidepressant drug. We conducted a systematic review of preclinical and clinical studies addressing the effects of amantadine in animal models of depression and in patients with depression. Methods: PubMed, Science Direct, and Web of Science were searched up to September 1, 2017 to identify clinical and preclinical studies. The following search terms were used: “amantadine AND depress*”; “amantadine AND mood”; “amantadine AND animal models AND antidepres*”; and “amantadine AND (forced swim, learned helplessness, reserpine, chronic mild stress, anhedonia, sucrose preference).” Results: Amantadine had antidepressant-like effects in animal models and appeared to potentiate the antidepressant effects of other antidepressants. These preclinical findings have received some support from the results of small open-label clinical trials, suggesting that amantadine can reduce depressive symptomatology and potentiate the antidepressant effects of monoaminergic drugs. In addition to its glutamatergic and dopaminergic effects, the potential antidepressant-like effects of amantadine have been linked to molecular and cellular actions, such as increased expression of neurotrophic factors (e.g., brain-derived neurotrophic factor), activation of σ1 receptors, decreased corticosterone levels, and decreased inflammatory response to stress. Conclusion: Amantadine is an interesting candidate as new antidepressant drug for the treatment of depression.

AIM: To evaluate changes in blood pressure and heart rate in patients undergoing dental implant procedures, considering the dental setting as the main variable.METHODS: Fifty-five patients who underwent dental implant surgery were evaluated. Thirty-seven were treated at a university clinic and 18 were treated at a private office. Blood pressure and heart rate were measured at the following time-points: at the appointment prior to surgery (T0), immediately before the surgical procedure (T1), during anesthesia (T2), during implant installation (T3), immediately after the surgical procedure (T4) and at the first follow-up appointment after surgery (T5). The data were analyzed by two-way analysis of variance and Student's t-test.RESULTS: The university clinic patients had an increase in heart rate at T5 (t53=2.62, p<0.05) compared with private office patients. Systolic blood pressure in university clinic patients was higher at T2 (t53=2.86, p<0.01), T3 (t53=2.64, p<0.05), and T4 (t53=3.15, p<0.01). Diastolic blood pressure at T2 (t53=3.15, p<0.01) and T3 (t53=3.86, p<0.01) were also higher in university clinic patients.CONCLUSIONS: These results suggest that the dental setting is a relevant factor when planning dental implant surgery.

The aim of the present study was to evaluate the effects of sodium fluoride (NaF) on the male reproductive system. Adult male rats were exposed to NaF in drinking water for 30 days at three concentrations: 1.54 (control, tap water), 50 and 100 ppm. Body and organ weights, daily sperm production, sperm number and morphology were investigated. No difference was observed on the sperm number and morphology among the groups, as well as body weight and organ absolute and relative weights. Overall, despite the presence of a mild degree of dental fluorosis in the higher dose group, the results indicated that exposure to NaF at the doses used in the present study did not adversely affect sperm production and morphology of male rats.

OBJETIVO: Revisar os estudos clínicos controlados sobre a efetividade de plantas medicinais/fitoterápicos no transtorno de ansiedade generalizada. MÉTODO: Realizou-se uma busca (Medline, Web of Science, SciELO, Biblioteca Cochrane) por artigos originais utilizando as palavras ["plant OR phytomed* OR extract OR herbal OR medicinal (OR specific name plants)"] AND ("anxie* OR anxioly* OR tranquil* OR GAD"), delimitada a "human OR clinical trial OR randomized controlled trial OR meta-analysis OR review" e à língua inglesa. Os critérios de inclusão foram: estudos randomizados, comparativos e duplo-cegos. RESULTADOS: Foram selecionados sete dos 267 artigos encontrados. O Piper methysticum (kava-kava) foi o fitoterápico mais estudado, sendo sugerido um efeito ansiolítico. Entretanto, a maioria destes estudos incluiu outros transtornos de ansiedade e os dois estudos com transtorno de ansiedade generalizada apresentaram resultados contraditórios. Estudos isolados envolvendo Ginkgo biloba, Galphimia glauca, Matricaria recutita (camomila), Passiflora incarnata e Valeriana officinalis indicaram potencial efeito ansiolítico no transtorno de ansiedade generalizada. A Ginkgo biloba e a Matricaria recutita apresentaram um effect size ('d' de Cohen = 0,47 e 0,87) similar ou superior ao dos ansiolíticos atuais (0,17-0,38). Não foram localizados estudos com outras plantas. CONCLUSÃO: Apesar do potencial terapêutico dos fitoterápicos no transtorno de ansiedade generalizada, poucos ensaios clínicos controlados foram identificados, com a maioria apresentando limitações metodológicas.

OBJECTIVE: This work aimed to identify controlled trials, which evaluated effectiveness of herbal medicines in subjects suffering generalized anxiety disorder. METHOD: Controlled studies (randomized, comparative with placebo and/or standard drug, double-blind) were sought through electronic and hand-searches. The word strategy used "plant OR phytomed* OR extract OR herbal OR medicinal (OR specific name plants)" e "anxie* OR anxioly* OR tranquil* OR GAD", limited to "human OR clinical trial OR randomized controlled trial OR meta-analysis OR review". The search was restricted to English language. RESULTS: Piper methysticum presented an unequivocal anxiolytic effect, but most studies also included patients with other anxiety disorders (e.g. phobias). Isolated studies with Ginkgo biloba, Galphimia glauca, Matricaria recutita, Passiflora incarnata and Valeriana officinalis showed a potential use for anxious diseases. Despite this low number of studies, Ginkgo biloba and Matricaria recutita showed an effect size (Cohen's d = 0.47 to 0.87) similar or higher to standard anxiolytics drugs (benzodiazepines, buspirone and antidepressants - 0.17 to 0.38). No additional study with other plants was found. CONCLUSION: Despite the therapeutic potential of medicinal plants in generalized anxiety disorder, very few controlled trials assessing herbal medicines in generalized anxiety disorder were found. Additionally, these studies present serious flaw design.

Avaliou-se o efeito de um composto fitoterápico de Valeriana officinalis e Passiflora alata em dois modelos de memória em camundongos: habituação e esquiva inibitória tipo step-trough. Diazepam (1,0 e 2,5 mg/kg) foi empregado como controle positivo. Agudamente, a administração de diazepam (2,5 mg/kg) antes do treino prejudicou o desempenho na habituação e na esquiva inibitória. Por outro lado, a administração aguda do composto fitoterápico (40-160 mg/kg) antes do treino não alterou o comportamento dos camundongos nestes modelos. Tratamento com o composto fitoterápico por 15 dias também não alterou o comportamento dos animais. Nas doses empregadas não se observou alteração da atividade motora. Os dados sugerem que, diverso do diazepam, este fitoterápico ansiolítico composto de Valeriana officinalis e Passiflora alata não causa amnésia.

The effect of a compound combining Valeriana officinalis and Passiflora alata extracts was tested on two mouse memory models: habituation and step-through inhibitory avoidance. Diazepam (1.0 and 2.5 mg/kg) was used as a positive control. Acute diazepam (2.5 mg/kg) before training impaired the habituation and performance in the inhibitory avoidance. On the other hand, acute phytotherapeutic compound (40-160 mg/kg), also before the training session, did not alter mouse behavior in these models. Repeated (15 days) treatment with the compound also did not impair the habituation. At the doses used, no locomotor effect was found. Taken together, the results suggest that, contrary to diazepam, the anxiolytic Valeriana officinalis and Passiflora alata compound did not induce amnesia.

OBJETIVOS: Os benzodiazepínicos, pelos seus empregos como ansiolítico, hipnótico, miorrelaxante e anticonvulsivante, são muito prescritos. Os efeitos colaterais que comprometem o paciente são: diminuição da atividade psicomotora, interação com outras drogas, como o álcool, e o desenvolvimento de dependência. Neste estudo, avaliou-se a qualidade da orientação médica sobre esses efeitos colaterais. MÉTODOS: Foram entrevistados 120 pacientes (39 homens e 81 mulheres) com idade média de 48 anos que procuraram as farmácias de Curitiba, Paraná, para comprar benzodiazepínicos. Para avaliar as orientações médicas recebidas sobre os efeitos colaterais dos medicamentos, aplicou-se um questionário com perguntas abertas e estimuladas. RESULTADOS: Treze por cento dos pacientes relataram ter sido orientados sobre os três tipos principais de efeitos colaterais, 27% a respeito de pelo menos dois e 40% sobre pelo menos um, enquanto que 19% não recebeu nenhuma orientação. A qualidade da orientação não foi influenciada pelo grau de instrução do paciente, pela especialidade do médico prescritor e pelo tipo de atendimento (particular ou público). Houve predomínio da orientação ''não beber'' (85%), seguida do cuidado para operar máquinas e dirigir veículos (46%), e por último, a orientação sobre o desenvolvimento de dependência (31%). CONCLUSÃO: Os resultados sugerem que os médicos estavam mais preocupados com o risco de interação com o álcool, que pode ser fatal. O elevado número de pacientes que usavam a medicação de modo contínuo por mais de um ano (61%), o insucesso na interrupção da medicação (94%) e a pouca orientação sobre o tempo de uso do medicamento (22%) podem indicar a falta de preocupação do médico com a possível dependência induzida pelos benzodiazepínicos.

OBJECTIVES: Benzodiazepines are among the most prescribed drugs indicated as anxiolytics, hypnotics, myorrelaxants or antiepileptics. Their main side effects are: reduced psychomotor activities, interaction to other drugs, like alcohol, and the development of dependence. In the present study it was evaluated the quality of the medical directions given to patients about those side effects. METHODS: One hundred and twenty patients (39 men and 81 women), mean age of 48 years old, who visited pharmacies in Curitiba to buy prescribed benzodiazepines, were interviewed by an open or directive questionnaire designed to obtain the medical directions about benzodiazepines side effects. RESULTS: Directions about the three main benzodiazepines side effects were observed only in 13% of the patients, 27% had received at least two and 40% only one, while 19% reported no directions. It suggested that the medical orientation was precarious and its quality was not influenced by the patients' educational level, the kind of medical attendance or the specialty of the physician. The main orientation cited was ''don't drink'' (85%), followed by ''don't drive or operate machines'' (46%), while few orientations about the risk to develop dependence on benzodiazepines was observed (31%). CONCLUSION: This suggests that physicians were worried about the alcohol interaction risk, which can be dangerous for the patients. The high number of patients using benzodiazepines continuously for more than one year (61%), the unsuccessfully attempt to stop using BZD (94%) and the poor information about the duration of the treatment (22%) were all related to the low medical worry about dependence on benzodiazepines.

O presente artigo apresenta uma visão atualizada e ampla do tratamento farmacológico do transtorno de ansiedade generalizada (TAG). São revistos os medicamentos com eficácia comprovada em estudos controlados e atualmente disponíveis na clínica (benzodiazepínicos, buspirona, antidepressivos, betabloqueadores, antipsicóticos e extrato de kava-kava). A seguir, baseados nesses dados, propõe-se um algoritmo de tratamento do TAG. São apresentadas as principais linhas de pesquisa de novos fármacos ansiolíticos, descrevendo os principais achados clínicos e pré-clínicos.

This article presents an updated and broad perspective of the pharmacological treatment of generalized anxiety disorder (GAD). Medications proven to be efficacious in controlled studies and available in the clinic setting were reviewed (benzodiazepines, buspirone, antidepressives, beta-blocking agents, antipsychotics and kava-kava extract). From this data, an algorithm for GAD treatment is proposed. In addition, the main research lines on new anxiolytic drugs and their stage of clinical or pre-clinical development are presented.