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This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

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OBJECTIVE@#To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.@*METHODS@#Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.@*RESULTS@#Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).@*CONCLUSION@#Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

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OBJECTIVE@#To compare the therapeutic efficacy of governor vessel moxibustion combined with fluoxetine hydrochloride capsule, simple fluoxetine hydrochloride capsule and placebo moxibustion combined with fluoxetine hydrochloride capsule for mild to moderate depression with kidney-yang deficiency.@*METHODS@#A total of 126 patients with mild to moderate depression with kidney-yang deficiency were randomized into a governor vessel moxibustion group (42 cases, 2 cases dropped off), a western medication group (42 cases, 1 case dropped off) and a placebo moxibustion group (42 cases, 1 case dropped off). The western medication group was given fluoxetine hydrochloride capsule orally, 20 mg a time, once a day. On the basis of the treatment in the western medication group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the governor vessel moxibustion group, once a week; placebo moxibustion was applied in the placebo moxibustion group, once a week. Treatment of 8 weeks was required in the 3 groups. Before and after treatment, the scores of Hamilton depression scale-17 (HAMD-17), Asberg's rating scale for side effects (SERS) and TCM clinical symptom were compared, and the clinical efficacy was evaluated.@*RESULTS@#After treatment, the scores of HAMD-17, SERS and TCM clinical symptom were decreased compared before treatment in the 3 groups (P<0.05), the decrease ranges of above scores in the governor vessel moxibustion group were larger than those in the western medication group and the placebo moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the governor vessel moxibustion group, which was higher than 75.6% (31/41) in the western medication group and 80.5% (33/41) in the placebo moxibustion group (P<0.05).@*CONCLUSION@#Governor vessel moxibustion combined with fluoxetine hydrochloride capsule can improve the degree of depression and relieve the clinical symptoms in mild to moderate depression patients with kidney-yang deficiency, the efficacy is superior to simple fluoxetine hydrochloride capsule, and can reduce the fluoxetine hydrochloride capsule-induced adverse effect to a certain extent.

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Tecnologia: Inibidores da Recaptação de Serotonina-Norepinefrina (IRSNs): venlafaxina, desvenlafaxina e duloxetina. Indicação: Transtorno Depressivo Maior (TDM). Pergunta: Os antidepressivos IRSNSs (venlafaxina, desvenlafaxina e duloxetina), comparados a fluoxetina, são mais eficazes para alcançar remissão clínica e outros desfechos e são mais seguros, com menor taxa de abandono de tratamento devido a eventos adversos, no tratamento do transtorno depressivo maior em adultos? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED revisões sistemáticas com a ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Duas revisões sistemáticas com meta-análises de rede foram selecionadas, pois atenderam aos critérios de elegibilidade. Conclusão: Nas fases de indução e de manutenção do tratamento do TDM, as evidências de baixa a moderada certeza sugerem que os IRSNs são similares à fluoxetina quanto aos desfechos de eficácia (taxa de remissão clínica, taxa de recaídas em seis meses) e segurança (tipos de eventos adversos, taxa de abandono de tratamento devido a eventos adversos

Technology: Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): venlafaxine, desvenlafaxine,and duloxetine. Indication: Major Depressive Disorder (MDD). Question: Are SNRI antidepressants venlafaxine, desvenlafaxine, and duloxetine), compared to fluoxetine, more effective in achieving clinical remission and other outcomes, and are they safer with a lower treatment discontinuation rate due to adverse events in the treatment of major depressive disorder in adults? Methods: A literature search was conducted in the PUBMED database for systematic reviews using the AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2) tool. Results: Two systematic reviews with network meta-analyses were selected as they met the eligibility criteria. Conclusion: In the induction and maintenance phases of MDD treatment, low to moderate certainty evidence suggests that SNRIs are similar to fluoxetine in terms of efficacy outcomes (clinical remission rate, six-month relapse rate) and safety (types of adverse events, treatment discontinuation rate due to adverse events)

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Tecnologia: Pregabalina, benzodiazepínicos, bupropiona, fluoxetina. Indicação: Transtorno de ansiedade generalizada (TAG). Pergunta: A intervenção com pregabalina é mais eficaz e segura que a farmacoterapia disponível no SUS (ansiolíticos benzodiazepínicos ou antidepressivos) para alcançar remissão sintomática no tratamento do TAG? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED e EPISTEMONIKOS, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Resultados: Foi selecionada uma revisão sistemática, que atendeu aos critérios de elegibilidade. Conclusão: As evidências provenientes de uma meta-análise de rede, que possivelmente apresentam baixa certeza, sugerem que a eficácia da pregabalina no alívio sintomático da ansiedade não difere significativamente da dos medicamentos disponíveis no SUS, como fluoxetina, bupropiona e benzodiazepínicos. Contudo, as evidências indicam que a pregabalina possui maior aceitabilidade em comparação com esses medicamentos, refletida em uma menor taxa de descontinuação do tratamento

Technology: Pregabalin, benzodiazepines, bupropion, fluoxetine. Indication: Generalized Anxiety Disorder (GAD). Question: Is pregabalin more effective and safer than pharmacotherapy (benzodiazepine anxiolytics or antidepressants) available in the Brazilian Public Health System (BPHS) for achieving symptomatic remission in the treatment of GAD? Methods: A bibliographic survey was conducted in the PUBMED and EPISTEMONIKOS databases, following predefined search strategies. The methodological quality of the systematic reviews was assessed using the AMSTAR-2 tool (A MeaSurement Tool to Assess systematic Reviews version 2). Results: We selected a systematic review that met the eligibility criteria. Conclusion: The evidence from a network meta-analysis, which possibly presents low certainty, suggests that the efficacy of pregabalin in the symptomatic relief of anxiety does not significantly differ from that of the medications available in the SUS, such as fluoxetine, bupropion, and benzodiazepines. However, the evidence indicates that pregabalin has greater acceptability compared to these medications, reflected in a lower discontinuation rate of treatment

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Tecnologia: Antidepressivos Inibidores Seletivos da Recaptação de Serotonina fluoxetina, escitalopram, citalopram, sertralina e paroxetina. Indicação: Tratamento de adultos com transtorno depressivo maior. Pergunta: Existem diferenças nos efeitos sobre os desfechos de saúde entre o antidepressivo ISRS disponível no SUS (Fluoxetina) e os outros agentes ISRSs (citalopram, escitalopram, paroxetina e sertralina) disponíveis no Brasil para o tratamento de pacientes adultos com TDM? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas e incluída duas revisões sistemáticas. Conclusão: As evidências de muito baixa à moderada certeza sugerem que não existem diferenças significativas entre fluoxetina, citalopram, escitalopram, paroxetina e sertralina quanto aos efeitos sobre os desfechos de eficácia (remissão clínica, resposta clínica, taxa de recaída em seis meses) e segurança (abandono de tratamento devido a eventos adversos, tipos de eventos adversos) no tratamento de pacientes adultos com TDM, tanto na fase de indução quanto na de manutenção

Technology: Selective Serotonin Reuptake Inhibitors (SSRIs) fluoxetine, escitalopram, citalopram, sertraline, and paroxetine. Indication: Treatment of adults with major depressive disorder (MDD). Question: Are there differences in the effects on health outcomes between the SSRI antidepressant available in the Brazilian Public Health System (SUS) (fluoxetine) and other SSRI (citalopram, escitalopram, paroxetine, and sertraline) available in Brazil for the treatment of adult patients with MDD? Methods: Rapid review of evidence (overview) of systematic reviews, with a literature search conducted in the PUBMED database using a structured search strategy. The methodological quality of the systematic reviews was assessed with AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Two systematic reviews were selected and included. Conclusion: Evidence of very low to moderate certainty suggests that there are no significant differences between fluoxetine, citalopram, escitalopram, paroxetine, and sertraline regarding the effects on efficacy outcomes (clinical remission, clinical response, six-month relapse rate) and safety (treatment discontinuation due to adverse events, types of adverse events) in the treatment of adult patients with MDD, both in the induction and maintenance phases.

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Objective: Analyze lysosomotropic agents and their action on COVID-19 targets using the molecular docking technique. Methods: Molecular docking analyses of these lysosomotropic agents were performed, namely of fluoxetine, imipramine, chloroquine, verapamil, tamoxifen, amitriptyline, and chlorpromazine against important targets for the pathogenesis of SARS-CoV-2. Results: The results revealed that the inhibitors bind to distinct regions of Mpro COVID-19, with variations in RMSD values from 1.325 to 1.962 Å and binding free energy of -5.2 to -4.3 kcal/mol. Furthermore, the analysis of the second target showed that all inhibitors bonded at the same site as the enzyme, and the interaction resulted in an RMSD variation of 0.735 to 1.562 Å and binding free energy ranging from -6.0 to -8.7 kcal/mol. Conclusion: Therefore, this study allows proposing the use of these lysosomotropic compounds. However, these computer simulations are just an initial step toward conceiving new projects for the development of antiviral molecules.

Objetivo: aAnalisar agentes lisossomotrópicos e sua ação em alvos de COVID-19 usando a técnica de docking molecular. Métodos: Foram realizadas análises de docagem molecular destes agentes lisossomotrópicos, nomeadamente de fluoxetina, imipramina, cloroquina, verapamil, tamoxifeno, amitriptilina e clorpromazina contra alvos importantes para a patogenia do SARS-CoV-2. Resultados: Os resultados revelaram que os inibidores se ligam a regiões distintas do Mpro COVID-19, com variações nos valores de RMSD de 1.325 a 1.962 Å e energia livre de ligação de -5,2 a -4,3 kcal/mol. Além disso, a análise do segundo alvo mostrou que todos os inibidores se ligaram no mesmo sítio da enzima, e a interação resultante em uma variação de RMSD de 0,735 a 1.562 Å e energia livre de ligação variando de -6,0 a -8,7 kcal/mol. Conclusão: Portanto, este estudo permite propor o uso desses compostos lisossomotrópicos. No entanto, essas simulações em computador são apenas um passo inicial para a concepção de novos projetos para o desenvolvimento de moléculas antivirais.

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Objectives: The purpose of this study was to evaluate the mutagenic potential of fluoxetine and fluoxetine-galactomannan. Methods: Chromosomal aberration test and Salmonella typhimurium/microsome mutagenicity assay. Results: The results showed that fluoxetine (250 µg/mL) can cause chromosomal breaks of treated leukocytes and increase the frequency of reversion of the tester strains of S. typhimurium / microsome assay only at the highest concentration (5 mg/mL), while fluoxetine encapsulated in galactomannan did not cause these changes (leukocytes and S. typhimuriums strains). Conclusion: In summary, fluoxetine showed a mutagenic effect detectable only at high concentrations in both eukaryotic and prokaryotic models. Furthermore, the fluoxetine/galactomannan complex, in this first moment, prevented the mutagenicity attributed to fluoxetine, emphasizing that the present encapsulation process can be an alternative in preventing these effects in vitro.

Objetivos: avaliar o potencial mutagênico da fluoxetina e da fluoxetina-galactomanana. Métodos: Teste de aberração cromossômica e ensaio de mutagenicidade de Salmonella typhimurium /microssoma. Resultados: a fluoxetina (250 µg/mL) pode causar quebras cromossômicas de leucócitos tratados e aumentar a frequência de reversão das cepas testadoras de S. typhimurium /microssoma apenas na concentração mais alta (5 mg/mL), enquanto a fluoxetina encapsulada em galactomanano não causou essas alterações (leucócitos e cepas de S. typhimurium). Conclusão: a fluoxetina mostrou um efeito mutagênico detectável apenas em altas concentrações em modelos eucarióticos e procarióticos. Além disso, o complexo fluoxetina/galactomanan, neste primeiro momento, evitou a mutagenicidade atribuída à fluoxetina, ressaltando que o presente processo de encapsulamento pode ser uma alternativa na prevenção desses efeitos in vitro.

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Objective: this systematic review aims to compile literature data on the antimicrobial action of Selective Serotonin Reuptake Inhibitors (SSRI). Methods: To this end, the articles in this review were searched in the PubMed database between the years 2010 to 2020, using terms found in MESH as descriptors. The PRISMA flow diagram was used to analyze the process flow of the research. Later, inclusion and exclusion criteria and eligibility for data extraction and statistical analysis were applied. Results: Thus, of 252 articles found, 13 were used for this systematic review. The period in which there were more publications was in 2016-2017. All articles demonstrated the antimicrobial activity of ISRS, such as sertraline, fluoxetine, and paroxetine, in addition to their synergistic activity with some antifungals and antibacterial. Conclusion: With this, it could be concluded that the repositioning of non-antibiotic drugs that have antimicrobial activity is a promising alternative for the scientific community and, in the future, in clinical practice

Objetivo: compilar dados da literatura sobre a ação antimicrobiana dos Inibidores Seletivos de Recaptação de Serotonina (ISRS). Métodos: os artigos desta revisão foram pesquisados na base de dados PubMed, entre os anos de 2010 a 2020, utilizando, como descritores, termos encontrados no MESH. O fluxograma PRISMA foi utilizado para analisar o fluxo do processo da pesquisa. Posteriormente, foram aplicados os critérios de inclusão e exclusão e de elegibilidade para extração de dados e análise estatística. Resultados: dos 252 artigos encontrados, 13 foram utilizados para esta revisão sistemática. O período em que houve mais publicações foi em 2016-2017. Todos os artigos demonstraram a atividade antimicrobiana do ISRS, como sertralina, fluoxetina e paroxetina, além de sua atividade sinérgica com alguns antifúngicos e antibacterianos. Conclusão: o reposicionamento de medicamentos não antibióticos que possuam atividade antimicrobiana é uma alternativa promissora para a comunidade científica e, futuramente, na prática clínica.

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ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

RESUMO Antecedentes: A epilepsia apresenta comorbidades neuropsiquiátricas como depressão, transtorno bipolar e ansiedade. Os medicamentos que visam o tratamento da epilepsia podem ser úteis para a epilepsia e suas comorbidades neuropsiquiátricas. Objetivo: Investigar os efeitos da modulação serotonérgica em citocinas pró-inflamatórias e as convulsões no modelo de convulsão induzida por pentilenotetrazol (PTZ) em ratos. Métodos: Ratos Wistar machos foram injetados intraperitonealmente com serotonina, inibidor seletivo da recaptação da serotonina fluoxetina, sumatriptano agonista do receptor 5-HT1B / D ou solução salina 30 min antes do tratamento com PTZ. As crises comportamentais foram avaliadas pela escala de Racine. As concentrações de IL-1β, IL-6 e TNF-α no soro e tecido cerebral foram determinadas por ELISA. Resultados: A serotonina e a fluoxetina, mas não o sumatriptano, aliviaram as convulsões induzidas por PTZ ao prolongar os tempos de início das convulsões mioclônicas e tônico-clônicas generalizadas. O efeito anticonvulsivo da fluoxetina foi maior do que o da serotonina. Da mesma forma, a serotonina e a fluoxetina, mas não o sumatriptano, reduziram os aumentos induzidos por PTZ nos níveis de IL-1β e IL-6 no soro e no tecido cerebral. Nenhum dos medicamentos administrados, incluindo PTZ, alterou as concentrações de TNF-α. Conclusões: Nossos achados sugerem que a serotonina endógena e exógena exibe efeitos anticonvulsivantes por suprimir a neuroinflamação. Aparentemente, os receptores 5-HT1B / D não medeiam os efeitos anticonvulsivantes e anti-neuroinflamatórios da serotonina.

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Abstract Depression plays an important role in non-adherence to medical recommendations. Fluoxetine is a first line of depression treatment. This study aimed to evaluate adherence to drug therapy in fluoxetine users by different methods. A cross-section study was conducted with 53 depressed patients on fluoxetine for at least six months. Drug therapy adherence was assessed by validated questionnaires [Brief Medication Questionnaire (BMQ) and Morisky-Green test (MG)] and by the blood concentration of fluoxetine and its active metabolite norfluoxetine. Blood samples were taken before the daily first dose of fluoxetine. The plasmatic concentration of fluoxetine and norfluoxetine indicated that 58.5% volunteers were within the recommended therapeutic range and thus considered adherent to drug therapy. However, questionnaires indicated a non-adherent majority: 41.5% patients had a high degree of adherence in MG and only 13.2% were adherent to pharmacological treatment in BMQ. Most fluoxetine users showed a plasma concentration of fluoxetine and norfluoxetine within the therapeutic range, despite the low adherence to the drug therapy evaluated by the questionnaires. Thus, we suggest that plasma levels of fluoxetine and norfluoxetine could be used as the main method to check adherence to treatment.

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Tecnologia: Duloxetina e outros antidepressivos disponíveis no Sistema Único de Saúde (amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona). Indicação: Tratamento do primeiro episódio depressivo no transtorno de depressão maior em adultos. Pergunta: A duloxetina é mais eficaz e tolerável que a amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona para o tratamento do primeiro episódio de depressão maior em adultos? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada 1 revisão sistemática, que atendia aos critérios de inclusão. Conclusão: Os antidepressivos, comparados ao placebo, tinham maior taxa de resposta, taxa de remissão e taxa de descontinuação devido a efeitos colaterais, no tratamento de curto prazo. Duloxetina tinha taxa de resposta similar a amitriptilina, clomipramina, fluoxetina e bupropiona. Duloxetina e amitriptilina tinham maior taxa de remissão que fluoxetina. Comparando-se as taxas de abandono de tratamento devido a efeitos colaterais, clomipramina era menos seguro, amitriptilina, bupropiona e duloxetina eram parecidos entre si, e fluoxetina era o antidepressivo mais seguro

Technology: Duloxetine and other antidepressants available in the Brazilian Public Health System (amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion). Indication: Treatment of the first depressive episode in adult major depressive disorder. Question: Is duloxetine more effective and tolerable than amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion for the treatment of first episode of major depression in adults? Methods: Rapid response review of evidence (overview) from systematic reviews, with a bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Methodological Quality Assessment of Systematic Reviews). Results: One systematic review was selected, which met the inclusion criteria. Conclusion: In short-term treatment, antidepressants, compared to placebo, had a higher rate of response, rate of remission and rate drop-out due to side effects. Duloxetine had a similar response rate to amitriptyline, clomipramine, fluoxetine and bupropion. Duloxetine and amitriptyline had higher remission rates than fluoxetine. Comparing rates of dropout due to side effects, clomipramine had the worst rates, amitriptyline, bupropion, and duloxetine were similar to each other, and fluoxetine had the better rates

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HIGHLIGHTS Fluoxetine increases the metabolic rate and excretion of ammonia in both species. O:N ratio in fish showed higher values in the highest concentrations of fluoxetine. The LC50 - 96 hour values of Palaemon pandaliformis represented greater toxicity. Both species are a good biological model for fluoxetine exposure studies.

Abstract Fluoxetine is an emerging pollutant that acts as a selective serotonin reuptake inhibitor (SSRI) and being a hydrolytic molecule that is photolytically stable and accumulaties in biological tissues, its disposal in the aquatic environment can interfere with the physiology of fish and shrimp. Thus, the objective of this study was to analyze the effects of fluoxetine on routine metabolism (metabolic rate, specific ammonia excretion and O:N ratio) of Deuterodon iguape and Palaemon pandaliformis. For this, five groups of each species, were exposed to different concentrations of fluoxetine for 24 hours (D. iguape) and 2 hours (P. pandaliformis). The results demonstrated that in D. iguape exposure to fluoxetine significantly increased both the metabolic rate by 75%, 85%, 55% and 50% for concentrations of 0.05; 0.1; 0.5 and 1.0 mgL-1, respectively, and the specific ammonia excretion by 40%, 48% and 20% for concentrations of 0.05; 0.1 and 0.5 mgL-1, respectively, when compared with their control. The O:N ratio was statistically greater in concentrations of 0.5 and 1.0 mgL-1. Concerning P. pandaliformis, exposure to fluoxetine increased metabolic rate at concentrations 30.0 and 60.0 µgL-1, and also increased specific ammonia excretion at concentrations 10.0, 30.0 and 60.0 µgL-1, when compared with the control group. It was concluded that exposure to fluoxetine increases the routine metabolism of both species and that at the concentration 1.0 mgL-1, Deuterodon iguape required different energy substrates.

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O objetivo deste estudo foi analisar os efeitos do estresse crônico sobre a periodontite apical (PA) induzida em ratos, e avaliar os efeitos do uso da Fluoxetina (antidepressivo da classe dos inibidores da recaptação de serotonina) e do Propranolol (bloqueador beta-adrenérgico), associados ou não, na modulação inflamatória e na reabsorção óssea periapical de ratos estressados. Foram utilizados 40 ratos divididos em cinco grupos: Grupo controle não-estressado (NS); Grupo controle estressado com administração de solução fisiológica (SS); Grupo estressado com administração de Fluoxetina (SF); Grupo estressado com administração de Propranolol (SP); Grupo estressado com administração de Fluoxetina e Propranolol (SFP). Os animais dos grupos estressados foram submetidos ao protocolo de estresse crônico imprevisível durante 6 semanas e as respectivas medicações foram administradas diariamente, via gavagem, ao longo de todo o período experimental. A PA foi induzida em todos os grupos após 21 dias do início do protocolo de estresse e ao final da 6ª semana, os animais foram eutanasiados e as hemimandíbulas e hemimaxilas removidas. Posteriormente foram realizadas as seguintes análises: a) da massa corporal; b) dos níveis séricos de corticosterona por radioimunoensaio; c) dos níveis séricos hormonais e inflamatórios por ensaio Multiplex; e) histomorfométrica por coloração com hematoxilina e eosina; f) da estrutura óssea periapical através de microtomografia computadorizada (micro-CT); g) da expressão gênica de biomarcadores relacionados à atividade osteoclástica, citocinas inflamatórias e metaloproteinases na região periapical por RT-PCR. Ao final do experimento os animais estressados apresentaram menor ganho de massa corporal, níveis séricos de ACTH significativamente mais altos, atividade inflamatória mais intensa e maiores volumes de lesão periapical quando comparados aos animais do grupo controle NS. Os grupos tratados SF, SP e SFP apresentaram menores volumes de lesão periapical quando comparados ao grupo controle SS, e o grupo SP apresentou menor intensidade do infiltrado inflamatório. O teste de RT-PCR mostrou maior expressão de RANKL e TRAP no grupo controle SS, bem como maior expressão de IL-6, IL-10 e IL-17 e MMP-8 quando comparado ao grupo controle NS. Na comparação em relação ao grupo controle SS, o grupo SF apresentou maior expressão de OPG, e menor expressão de IL-6 e IL-17; o grupo SP apresentou maior expressão de OPG e menor expressão de IL-6, IL-10, IL-17, MMP-8 e MMP-13, e o grupo SFP apresentou menor expressão de RANKL, TRAP, IL-6, IL-10, IL-17, MMP-8 e MMP-13. Foi concluído que o estresse crônico influenciou negativamente a patogênese da PA e ambos os medicamentos avaliados, bem como sua associação, tiveram efeitos positivos na prevenção da perda óssea e modulação inflamatória.

The aim of this study was to analyze the effects of chronic stress on induced apical periodontitis (AP) in rats, and to evaluate the effects of the use of fluoxetine (antidepressant known as selective serotonin reuptake inhibitor), and of Propranolol (beta-adrenergic blocker), associated or not, in inflammatory modulation and periapical bone resorption in stressed rats. Forty rats were divided into five groups: Unstressed control group (NS); Stressed control group with saline solution administration (SS); Stressed group with administration of Fluoxetine (SF); Stressed group with administration of Propranolol (SP); Stressed group with administration of Fluoxetine and Propranolol (SFP). The animals in the stressed groups were submitted to the unpredictable chronic stress paradigm for 6 weeks and the respective medications were administered daily, via gavage, throughout the entire experimental period. AP was induced in all groups, 21 days after the beginning of the stress paradigm, and at the end of the 6th week, the animals were euthanized and the hemi-mandibles removed for the following analyses: a) body weight b) serum corticosterone levels by radioimmunoassay; c) hormone and inflammatory serum levels by Multiplex assay; e) histomorphometric staining with hematoxylin and eosin; f) the periapical bone structure through computerized microtomography; g) gene expression related to osteoclastic activity, inflammatory cytokines and metalloproteinases in the periapical region by RT-PCR. At the end of the experiment, the stressed animals showed lower body weight gain, significantly higher levels of ACTH, more intense inflammatory infiltrate and higher volumes of periapical lesion when compared to animals in the NS control group. The treated groups SF, SP and SFP had smaller volumes of periapical lesion when compared to the SS control group and the SP group had lower intensity of inflammatory infiltrate. The RT-PCR test showed higher expression of RANKL and TRAP in the stressed control group, as well as higher expression of IL-6, IL-10, IL-17 and MMP-8 when compared to the NS control group. In comparison with the SS control group, the SF group showed higher expression of OPG, and lower expression of IL-6 and IL-17; the SP group showed higher expression of OPG and lower expression of IL-6, IL-10, IL-17, MMP-8 and MMP-13 and the SFP group showed lower expression of RANKL, TRAP, IL-6, IL-10, IL-17, MMP-8 and MMP-13. It was concluded that chronic stress negatively influenced the pathogenesis of apical periodontitis and both medications evaluated, as well as its association, had positive effects in preventing bone loss and inflammatory modulation.

ABSTRACT

In the present study, antidepressant-like activity of ethanol extract of leaves of Caesalpinia pulcherrima was evaluated in Swiss young male albino mice. Stress was induced in mice by subjecting them to unpredictable mild stress for 21 successive days. Ethanol extract of the leaves (100, 200 and 400 mg/ kg, p.o.) and fluoxetine (20 mg/kg, p.o.) were administered for 21 consecutive days to separate groups of unstressed and stressed mice. Ethanol extract (200 and 400 mg/kg) and fluoxetine significantly decreased immobility period of unstressed as well as stressed mice in tail suspension test (TST). However, the lowest dose (100 mg/kg) of the extract also significantly decreased immobility period of stressed mice in TST. The extract significantly restored reduced sucrose preference in stressed mice. There was no significant effect on locomotor activity of mice. Ethanol extract of the leaves significantly decreased plasma nitrite and corticosterone levels; brain MAO-A activity and MDA level; and increased brain reduced glutathione and catalase activity in unstressed as well as stressed mice as compared to their respective vehicle treated controls. Thus, ethanol extract of leaves of Caesalpinia pulcherrima showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO-Aactivity, reduction of oxidative stress and plasma corticosterone levels.

ABSTRACT

Abstract Objectives This study aimed to explore the effect of antidepressant treatment on the HPA axis, changes in depression score, and serum levels of TNF-α in depressed infertile women. Methods In this randomized controlled trial research, 60 infertile women who had undergone in vitro fertilization (IVF) treatment with depression scores between 16-47 were divided into two groups. The intervention group with fluoxetine capsule was under treatment for two months before the embryo transfer, while the control group was given placebo. Depression score, serum levels of tumor necrosis factor alpha (TNF-α) as well as cortisol hormone levels were measured and recorded both before and after the intervention. The data were analyzed using SPSS version 21 software. Results We analyzed the data related to 55 subjects who had undergone embryo transfer. 7 subjects in the intervention group and 3 in the control group got pregnant. We observed a significant decrease in the depression score (p < 0/001) and serum levels of cortisol (p = 0/001) in the intervention group. There was a significant increase in the serum levels of TNF-α in the intervention group (p < 0/001). There was a significant difference between the two groups in the number of pregnancies (p = 0.04). However, there was no statistical difference between them with regard to the number of harvested oocytes (p = 0.174). Discussion Decrease in depression score and cortisol level, and an increase in the levels of TNF-α in the intervention group caused any changes in the number of oocytes in comparison with the control group. However, the number of pregnancies was larger in the intervention group.

ABSTRACT

Abstract Background: EpiFibro (Brazilian Epidemiological Study of Fibromyalgia) was created to study patients with fibromyalgia (FM). Patients were included since 2011 according to the classification criteria for FM of the American College of Rheumatology of 1990 (ACR1990). Objective: To analyze the therapeutic measures prescribed by Brazilian physicians. Materials and methods: Cross-sectional study of a multicenter cohort. The therapeutic measures were described using descriptive statistics. Results: We analyzed 456 patients who had complete data in the registry. The mean age was 54.0 ± 11.9 years; 448 were women (98.2%). Almost all patients (98.4%) used medications, 62.7% received health education, and less than half reported practicing physical exercise; these modalities were often used in combination. Most patients who practiced exercises practiced aerobic exercise only, and a significant portion of patients combined it with flexibility exercises. The most commonly used medication was amitriptyline, followed by cyclobenzaprine, and a minority used medication specifically approved for FM, such as duloxetine and pregabalin, either alone or in combination. Combinations of two or three medications were observed, with the combination of fluoxetine and amitriptyline being the most frequent (18.8%). Conclusion: In this evaluation of the care of patients with FM in Brazil, it was found that the majority of patients are treated with a combination of pharmacological measures. Non-pharmacological methods are underused, with aerobic exercise being the most commonly practiced exercise type. The most commonly prescribed single drug was amitriptyline, and the most commonly prescribed combination was fluoxetine and amitriptyline. Drugs specifically approved for FM are seldom prescribed.(AU)

ABSTRACT

A case report of a patient with pseudo bulbar affect previous treatments included haloperidol (10mg), Inosina pranobex (600mg), clozapine (600mg), olanzapine (20mg), carbamazepine (200mg), paroxetine (20mg), phenobarbital (100mg) and topiramate (50mg), all suspended at August 2016, with current use of quetiapine (700mg) Chlorpromazine (600mg) (+ 200mg on demand of aggression), clonazepam (4 mg), valproate 2500 mg, propranolol (40mg). that was successful treated with off label treatment (dextromethorphan plus quinidine). Previous Brief Psychiatric Rating Scale and Clinical Global Impression-Improvement was applied after and before treatment with dextromethorphan (20mg) plus fluoxetine (20 mg, further increased to 40 mg). Previous Brief Psychiatric Rating Scale BPRS score 56 points and Clinical Global Impression-Severity (CGI-S) Score was 6 (severely ill). The addition of dextromethorphan (20mg) and fluoxetine (20 mg, further increased to 40 mg), allowed clear improvement of pathological crying and outbursts, with BPRS decrease of 8 points and Clinical Global Impression-Improvement (CGI-I) 2 (much improved) ­ especially pertaining to PBA related symptoms and aggressive behavior. There were no noticeable side-effects. This case report shown an interesting clinical response. It's could be a great alternative in treatment of pseudobulbar affect symptoms. Even though an only case and a great clinical study be necessary. (AU)

ABSTRACT

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)

Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)

ABSTRACT

ABSTRACT Purpose: To compare the efficacy and safety of available selective serotonin reuptake inhibitors (SSRIs) in order to find the most effective drug with the least number of side effects in treatment of premature ejaculation (PE). Materials and Methods: This study was a randomized clinical trial. Four hundred and eighty patients with PE in the 4 groups referred to Imam Reza hospital Tehran, Iran from July 2018 to February 2019 were enrolled in the study. The patients received sertraline 50mg, fluoxetine 20mg, paroxetine 20mg and citalopram 20mg, every 12 hours daily. The intravaginal ejaculatory latency time (IELT) before treatment, fourth and eighth weeks after treatment was recorded by the patient's wife with a stopwatch. Results: Mean IELT before, 4 and 8 weeks after treatment in four groups were: sertraline 69.4±54.3, 353.5±190.4, 376.3±143.5; fluoxetine 75.5±64.3, 255.4±168.2, 314.8±190.4; paroxetine 71.5±69.1, 320.7±198.3, 379.9±154.3; citalopram 90.39±79.3, 279.9±192.1, 282.5±171.1 seconds, respectively. The ejaculation time significantly increased in all groups (p <0.05), but there was no significant difference between the groups (P=0.75). Also, there was no significant difference in drugs side effects between groups (p >0.05). The most common side effects were drowsiness and dyspepsia, which were not severe enough to cause discontinuation of the drug. Conclusions: All available SSRIs were effective and usually had no serious complications. In patients who did not respond to any of these drugs, other SSRI drugs could be used as a salvage therapy.