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1.
J Matern Fetal Neonatal Med ; 36(1): 2162817, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36599445

RESUMO

OBJECTIVE: Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk for gestational diabetes mellitus (GDM) is inconsistent. We perform a systematic review and meta-analysis to assess the GDM risk associated with antidepressant exposure during pregnancy. METHODS: We systematically searched the PubMed and EMBASE databases until December 2021. We sought observational studies assessing the association between gestational antidepressant use and GDM. RESULTS: Five observational studies were included in the analysis. Mothers exposed to antidepressants during pregnancy were at a significantly increased risk for GDM (relative risk [RR] 1.20, 95% confidence interval [CI] 1.11-1.30; p < .001). However, after considering confounding by indication, we observed no significant effect of antidepressant use during pregnancy on the risk of GDM (RR 1.13, 95% CI 1-1.28; p = .054; I2 = 0%). Independent of clinical indication, subgroup analysis based on individual antidepressants suggested that the risk was increased by venlafaxine or amitriptyline use, but not by selective serotonin reuptake inhibitors. CONCLUSIONS: The significant association between antidepressant exposure during pregnancy and GDM may be overestimated due to confounding by indication. However, the evidence remains insufficient, particularly for specific drug classes.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/tratamento farmacológico , Antidepressivos/efeitos adversos , Cloridrato de Venlafaxina , Amitriptilina
2.
J Clin Psychiatry ; 84(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36602927

RESUMO

Objective: While poor neonatal adaptation syndrome (PNAS) has been particularly well described among infants exposed to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), this is not the case for second-generation antipsychotics (SGAs). In 2011, the US Food and Drug Administration (FDA) issued a drug safety warning regarding fetal antipsychotic exposure and risk for PNAS and extrapyramidal symptoms (EPS). The primary objective of this study was to examine the risk for PNAS among infants exposed to SGAs compared to SSRI/SNRI-exposed infants, leveraging the prospective, longitudinal design of the National Pregnancy Registry for Psychiatric Medications (NPRPM).Methods: The NPRPM is a prospective pharmacovigilance program in which pregnant women, aged 18-45 years, are enrolled and followed prospectively. Medical records were systematically reviewed and data abstracted using a checklist of PNAS and EPS symptoms specifically outlined in the FDA drug safety warning. The two study groups included infants exposed to an SGA during pregnancy and infants exposed to an SSRI/SNRI during pregnancy. The primary outcome was the presence of at least one or more PNAS symptoms during the first month of life. Other neonatal outcomes following exposure to the medication of interest, including preterm birth, neonatal intensive care unit (NICU) admission, rates of EPS, and whether infants were discharged home with their mothers, are also reported.Results: Of the 2,145 women enrolled in this study as of December 16, 2020, a total of 373 women and their infants (n = 384) were eligible for inclusion (n = 193 SGA-exposed infants and 191 SSRI/SNRI-exposed infants). Among SGA-exposed infants, 32.6% (63/193) experienced at least 1 PNAS sign compared to 34.6% of infants (66/191) in the SSRI/SNRI-exposed group. The majority of infants in each group showed no symptoms of PNAS. No differences were observed between the two groups with respect to rates of preterm birth, NICU admission, prevalence of EPS, and timing of infants being discharged home with their mothers.Conclusions: PNAS symptomatology was comparable among infants exposed prenatally to an SGA or to an SSRI/SNRI. These preliminary findings provide an estimated risk of PNAS among infants exposed to SGAs of roughly 30%. Interestingly, these findings are also consistent with estimates in the literature of PNAS in SSRI/SNRI-exposed infants, suggesting a possible common pathway underlying this phenomenon.Trial Registration: ClinicalTrials.gov identifier: NCT01246765.


Assuntos
Antidepressivos , Antipsicóticos , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Sistema de Registros , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos
3.
Phytomedicine ; 109: 154566, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610126

RESUMO

BACKGROUND: Depression is one of the most serious mental illnesses worldwide that endangers the health of people. The pathogenesis of depression is complex and is associated with abnormal neurotransmitter levels, activation of the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, and gut flora-related disorders. However, most of the current pharmacological therapies used to manage depression are inconsistent and are associated with side effects. Owing to their low toxicity and wide availability in nature, polysaccharides are gradually attracting attention and are being discovered to exert direct or indirect antidepressant effects. PURPOSE: In this review, we have summarized the classification, dosage, and experimental models to study polysaccharides with antidepressant effects obtained from different sources. We have also reviewed the protective effects and underlying mechanisms of these polysaccharides in depression by modulating inflammation, the HPA axis, and intestinal flora. METHODS: We searched the PubMed, Web of Science, and Google scholar databases and included studies that reported the use of polysaccharides in treating depression. RESULTS: The unique benefits of natural polysaccharides as antidepressants lie in their potential to modulate inflammation, regulate the HPA axis, and regulate intestinal flora, giving full play to their antidepressant effects via multiple pathways and targets. CONCLUSION: Natural polysaccharides may be a promising resource for use as adjuvant antidepressant therapy. Our study might therefore provide evidence for the development of polysaccharide resources as antidepressants.


Assuntos
Depressão , Sistema Hipotálamo-Hipofisário , Humanos , Depressão/tratamento farmacológico , Sistema Hipófise-Suprarrenal , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo
4.
Cytokine ; 162: 156115, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36599202

RESUMO

Women with breast cancer (BC) are often combined with psychological disorder such as depression and anxiety. Depression is associated or correlated with increased toxicity and severity of physical symptoms. However, the mechanism of BC progression related to the regulation of emotion-related circuitry remains to be further explored. The study aims to investigate indoleamine 2,3-dioxygenase (IDO) pathway mechanism underlying stress-induced progression of BC. BC cell line 4T1 was subcutaneously inoculated into BALB/c mice, and they then received daily chronic unpredictable mild stressors (CUMS) for 12 weeks. Depression-like behavior tests were conducted, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and novelty suppressed feeding test (NSF). The levels of 5-Hydroxytryptamine (5-HT) and inflammatory factors, IL-6, CXCL1, IL-10 and IL-4 were measured by enzyme linked immunosorbent assay (ELISA) of mouse serum. Immunohistochemical staining was performed to detect Ki67- or FOXP3-positive tumor cells. The status of IDO signaling pathway was assessed by immunoblotting analysis. CUMS induced depression-like behaviors, decreased the level of 5-HT, promoted tumor progression, enhanced the immunohistochemical staining of Ki-67, and promoted the activation of IDO signaling pathway in BC mice. The IDO signaling pathway was disrupted in mice by lentiviral transduction of shRAN-IDO. Lentivirus-mediated IDO knockdown attenuated CUMS-induced depression-like behaviors, increased the level of 5-HT, inhibited tumor progression, and reduced the immunohistochemical staining of Ki-67 in BC mice. The present study suggests that disruption of IDO signaling pathway alleviates CUMS-induced depression-like behaviors and inhibits tumor progression in BC mice.


Assuntos
Depressão , Neoplasias , Feminino , Camundongos , Animais , Depressão/psicologia , Antidepressivos/farmacologia , Serotonina/metabolismo , Antígeno Ki-67/metabolismo , Transdução de Sinais , Estresse Psicológico/metabolismo , Modelos Animais de Doenças , Comportamento Animal
5.
J Med Chem ; 66(1): 371-383, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36598095

RESUMO

Inadequate bioavailability is one of the most critical reasons for the failure of oral drug development. However, the way that substructures affect bioavailability remains largely unknown. Serotonin transporter (SERT) inhibitors are first-line drugs for major depression disorder, and improving their bioavailability may be able to decrease side-effects by reducing daily dose. Thus, it is an excellent model to probe the relationship between substructures and bioavailability. Here, we proposed the concept of "nonbioavailable substructures", referring to substructures that are unfavorable to bioavailability. A machine learning model was developed to identify nonbioavailable substructures based on their molecular properties and shows the accuracy of 83.5%. A more potent SERT inhibitor DH4 was discovered with a bioavailability of 83.28% in rats by replacing the nonbioavailable substructure of approved drug vilazodone. DH4 exhibits promising anti-depression efficacy in animal experiments. The concept of nonbioavailable substructures may open up a new venue for the improvement of drug bioavailability.


Assuntos
Transtorno Depressivo Maior , Proteínas da Membrana Plasmática de Transporte de Serotonina , Ratos , Animais , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Disponibilidade Biológica , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/química , Transtorno Depressivo Maior/tratamento farmacológico
6.
BMC Psychiatry ; 23(1): 17, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624454

RESUMO

BACKGROUND: Maladaptation of the HPA (hypothalamic-pituitary-adrenal) axis plays an important role in depression-like behaviour, but the specific molecular mechanisms are unknown. Here, we determined the roles of CRHR1 (corticotrophin releasing hormone receptor 1) and nectin3 in LPS (lipopolysaccharide)-induced depression-like behaviour in mice. METHODS: C57BL/6 male mice were intraperitoneally injected with LPS (0.83 g/kg), and the open field, novelty-suppressed feeding, forced swimming, and tail suspension tests were performed after intraperitoneal injections of saline or antalarmin (20 mg/kg). The hippocampal mRNA levels of CRHR1 and nectin3 were determined by quantitative reverse transcription-PCR. The hippocampal protein levels of CRHR1, nectin3, and calbindin were measured by western blotting. The CORT (corticosterone) levels in the blood were measured by ELISA kits. RESULTS: Antalarmin alleviated LPS-induced depression-like behaviour in male mice. Furthermore, antalarmin significantly inhibited changes in CRHR1, nectin3 and calbindin levels in the hippocampus and reduced the increase in CORT levels in LPS-treated mice. CONCLUSION: CRHR1antagonist showed antidepressant effects in LPS-induced depressive mice, and CRHR1/nectin3 signalling may play a crucial role in this process.


Assuntos
Depressão , Receptores de Hormônio Liberador da Corticotropina , Animais , Masculino , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo , Sistema Hipotálamo-Hipofisário/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores
7.
Psychopharmacology (Berl) ; 240(2): 373-389, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36645465

RESUMO

RATIONALE: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results. OBJECTIVES AND METHODS: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5-50 mg/kg, intragastric-i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg). RESULTS: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally-i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous-s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice. CONCLUSION: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression.


Assuntos
Depressão , Indolizinas , Masculino , Feminino , Animais , Camundongos , Depressão/tratamento farmacológico , Depressão/metabolismo , Serotonina/metabolismo , Simulação de Acoplamento Molecular , Atividade Motora , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Natação , Indolizinas/farmacologia , Elevação dos Membros Posteriores
8.
Cell Rep Med ; 4(1): 100906, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36652915

RESUMO

Goodwin et al.1 report a single 25 mg dose of psilocybin has an antidepressant effect short-term in medication-resistant depression. Unanswered questions include drug blood level as a guide to dose, psychedelic effects relationship to antidepressant benefit, and potential suicide risk of psilocybin.


Assuntos
Alucinógenos , Psilocibina , Humanos , Psilocibina/farmacologia , Psilocibina/uso terapêutico , Alucinógenos/farmacologia , Alucinógenos/uso terapêutico , Antidepressivos/efeitos adversos
9.
J Psychiatr Pract ; 29(1): 15-30, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649548

RESUMO

BACKGROUND: Depression in the elderly requires different treatment options because therapies that are commonly used for depression in younger patients show different effects later in life. Treatment options for late-life depression (LLD) are summarized in this article. METHODS: A literature search in Medline/PubMed performed in June 2020 identified 83 relevant studies. RESULTS: Pharmacotherapy with selective serotonin reuptake inhibitors can be an effective first-line treatment in LLD, but >50% of elderly patients do not adequately respond. Switching to other selective serotonin reuptake inhibitors or augmenting with mood stabilizers or antipsychotics is often effective in achieving a therapeutic benefit. Severely depressed patients with a high risk of suicidal behavior can be treated with electroconvulsive therapy. Psychotherapy provides a measurable benefit alone and when combined with medication. LIMITATIONS: LLD remains an underrepresented domain in research. Paucity of data concerning the effect of specific therapies for LLD, heterogeneity in the quality of study designs, overinterpretation of results from meta-analyses, and discrepancies between study results and guideline recommendations were often noted. CONCLUSIONS: Treating LLD is complex, but there are several treatment options with good efficacy and tolerability. Some novel pharmaceuticals also show promise as potential antidepressants, but evidence for their efficacy and safety is still limited and based on only a few trials conducted to date.


Assuntos
Antipsicóticos , Humanos , Idoso , Depressão/tratamento farmacológico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Psicoterapia
10.
J Psychiatr Pract ; 29(1): 58-70, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649554

RESUMO

OBJECTIVE: Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS: The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS: Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION: Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.


Assuntos
Depressão , Pancreatite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Doença Aguda , Depressão/tratamento farmacológico , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Antidepressivos/efeitos adversos , Mianserina/efeitos adversos , Antidepressivos Tricíclicos/efeitos adversos
12.
Medicina (Kaunas) ; 59(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36676742

RESUMO

Pharmacotherapy for major depressive disorder (MDD) typically consists of trial-and-error and clinician preference approaches, where patients often fail one or more antidepressants before finding an optimal regimen. Pharmacogenomics (PGx) can assist in prescribing appropriate antidepressants, thereby reducing the time to MDD remission and occurrence of adverse drug events. Since many antidepressants are metabolized by and/or inhibit cytochrome P450 enzymes (e.g., CYP2C19 or CYP2D6), drug-induced phenoconversion is common in patients on antidepressant combinations. This condition influences the interpretation of a patient's PGx results, overall risk of ineffective/adverse medication response due to multi-drug interactions, and the recommendations. This complex case describes a patient with MDD, generalized anxiety disorder, and chronic pain who experienced a fall due to excessive sedation following a prescribing cascade of fluoxetine, bupropion, and doxepin. These antidepressants delivered a significant additive sedative effect and interacted with the patient's hydrocodone, potentially contributing to uncontrolled pain, upward dose titration of hydrocodone, and a higher overall sedative burden. The PGx results and drug-induced phenoconversion described in this case report explain the patient's excessive sedation and possibly ineffective/toxic antidepressant and opioid treatment. This case report also illustrates how a more timely multi-drug interaction assessment (preferably in conjunction with preemptive PGx testing) may have informed a different prescribing pattern, reduced/avoided a prescribing cascade, and potentially prevented a drug-related fall.


Assuntos
Transtorno Depressivo Maior , Farmacogenética , Humanos , Farmacogenética/métodos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Hidrocodona/uso terapêutico , Antidepressivos/efeitos adversos , Fluoxetina/uso terapêutico
13.
Curr Opin Psychiatry ; 36(2): 134-139, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36705012

RESUMO

PURPOSE OF REVIEW: To provide an overview of recently published work on anxiety, focusing on generalized anxiety disorder (GAD) and its treatment. RECENT FINDINGS: Self-reported anxiety symptoms were highly prevalent during the COVID-19 global pandemic in both the general population and in selected groups. There remains divided opinion about whether internet-based cognitive behavioural therapy (CBT) is noninferior to face-to-face CBT for GAD. A systematic review of drug treatment for GAD showed efficacy for selective serotonin reuptake inhibitors (SNRIs), agomelatine, and quetiapine. There may be a place for repetitive transcranial magnetic stimulation in the treatment of GAD. There was some evidence of efficacy for complementary therapies, including physical exercise, yoga, acupuncture, and Withania somnifera (ashwagandha). However, a systematic review of cannabidiol and tetrahydrocannabinol found insufficient evidence of efficacy in anxiety disorders. SUMMARY: Antidepressants and quetiapine show efficacy in the treatment of GAD. Internet-based psychological interventions have a place in the treatment of GAD when face-to-face treatment is inaccessible. There is increasing evidence for the use of physical exercise in the management of GAD. Some other complementary therapies, including cannabinoids, require further, methodologically sound, research.


Assuntos
COVID-19 , Terapia Cognitivo-Comportamental , Humanos , Fumarato de Quetiapina/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Antidepressivos/uso terapêutico
14.
Eur J Med Chem ; 248: 115091, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638711

RESUMO

Psychiatric and neurological disorders affect millions of people worldwide. Currently available treatments may help to improve symptoms, but they cannot cure the diseases. Therefore, there is an urgent need for potent and safe therapeutic solutions. 8-Amide and 8-carbamatecoumarins were synthetized and evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Comparison between both scaffolds has been established, and we hypothesized that the introduction of different substituents can modulate hMAO activity and selectivity. N-(7-Hydroxy-4-methylcoumarin-8-yl)-4-methylbenzamide (9) and ethyl N-(7-hydroxy-4-methylcoumarin-8-yl)carbamate (20) proved to be the most active and selective hMAO-A inhibitors (IC50 = 15.0 nM and IC50 = 22.0 nM, respectively), being compound 9 an irreversible hMAO-A inhibitor twenty-four times more active in vitro than moclobemide, a drug used in the treatment of depression and anxiety. Based on PAMPA assay results, both compounds proved to be good candidates to cross the blood-brain barrier. In addition, these compounds showed non-significant cytotoxicity on neuronal viability assays. Also, the best compound proved to have a t1/2 of 6.84 min, an intrinsic clearance of 195.63 µL min-1 mg-1 protein, and to be chemically stable at pH 3.0, 7.4 and 10.0. Docking studies were performed to better understand the binding affinities and selectivity profiles for both hMAO isoforms. Finally, theoretical drug-like properties calculations corroborate the potential of both scaffolds on the search for new therapeutic solutions for psychiatric disorders as depression.


Assuntos
Carbamatos , Inibidores da Monoaminoxidase , Humanos , Inibidores da Monoaminoxidase/química , Carbamatos/farmacologia , Simulação de Acoplamento Molecular , Monoaminoxidase/metabolismo , Antidepressivos/farmacologia , Relação Estrutura-Atividade
15.
J Pharmacol Sci ; 151(2): 63-71, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36707180

RESUMO

Mirtazapine, an atypical antidepressant, is known to enhance serotonergic transmission by inhibiting the 5-hydroxytryptamine (5-HT)1A, 5-HT2C, and 5-HT3 receptors. However, the mechanism of action on the 5-HT3 receptor remains unclear. We investigated the inhibitory mechanisms of mirtazapine on 5-HT3 receptors of NCB20 neuroblastoma cells using the whole-cell voltage-clamp method. Mirtazapine inhibited the 5-HT3 receptor currents in a concentration-dependent manner, and the inhibitory effect was influenced by the concentration of 5-HT. When mirtazapine was co-applied to 5-HT, the maximal response of the 5-HT3 receptor current was reduced and EC50 was increased, suggesting that mirtazapine might act as a non-competitive inhibitor. Inhibition of 5-HT3 current by mirtazapine was stronger in pre-application than in co-application, which suggests that mirtazapine might act as a closed state inhibitor. This finding was further supported by no use-dependency of the mirtazapine for 5-HT3 receptor inhibition. Finally, mirtazapine accelerated the desensitization and deactivation process in a concentration-dependent manner. The difference in recovery time showed that mirtazapine drastically influences the desensitization process than the deactivation process. These mechanistic characteristics of mirtazapine support the understanding of the relationship between the 5-HT3 receptor and atypical antidepressants.


Assuntos
Antidepressivos de Segunda Geração , Serotonina , Mirtazapina , Serotonina/farmacologia , Antidepressivos/farmacologia , Linhagem Celular Tumoral , Receptores 5-HT3 de Serotonina
16.
J Matern Fetal Neonatal Med ; 36(1): 2171288, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36710395

RESUMO

Background: While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy.Methods: We used a large administrative database to determine whether psychiatric medications are continued during pregnancy and predictors of continued medication treatment.Results: Of 2,672,656 women included in our analysis, 86,454 (3.1%) filled a pre-pregnancy prescription for an anxiolytic or antidepressant medication within 3 months of estimated conception. Of women who filled a pre-pregnancy prescription, 49.4%, 26.1%, and 20.1% filled subsequent prescriptions in the 1st, 2nd, and 3rd trimesters. Discontinuation rates ranged by pharmaceutical agent, from 16% for fluoxetine to 71% for alprazolam. White women and women over 25 were more likely to continue anxiolytic and antidepressant treatment during pregnancy.Conclusion: Because untreated and under-treated mental health conditions are linked to adverse maternal outcomes, high discontinuation rates may have important implications for maternal health.


Assuntos
Ansiolíticos , Complicações na Gravidez , Gravidez , Feminino , Humanos , Estados Unidos , Depressão/tratamento farmacológico , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Fluoxetina/uso terapêutico , Preparações Farmacêuticas , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/induzido quimicamente
17.
Proc Natl Acad Sci U S A ; 120(5): e2208344120, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36689653

RESUMO

Antibiotic resistance is an urgent threat to global health. Antidepressants are consumed in large quantities, with a similar pharmaceutical market share (4.8%) to antibiotics (5%). While antibiotics are acknowledged as the major driver of increasing antibiotic resistance, little attention is paid to the contribution of antidepressants in this process. Here, we demonstrate that antidepressants at clinically relevant concentrations induce resistance to multiple antibiotics, even following short periods of exposure. Antibiotic persistence was also enhanced. Phenotypic and genotypic analyses revealed the enhanced production of reactive oxygen species following exposure to antidepressants was directly associated with increased resistance. An enhanced stress signature response and stimulation of efflux pump expression were also associated with increased resistance and persistence. Mathematical modeling also predicted that antidepressants would accelerate the emergence of antibiotic-resistant bacteria, and persister cells would help to maintain the resistance. Overall, our findings highlight the antibiotic resistance risk caused by antidepressants.


Assuntos
Antibacterianos , Antidepressivos , Antibacterianos/farmacologia , Mutação , Antidepressivos/farmacologia , Resistência Microbiana a Medicamentos , Bactérias
19.
Eur J Med Chem ; 247: 115071, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36603509

RESUMO

There is clear evidence that the presence of inflammatory factors and impaired GABA-ergic neurotransmission in depressed patients is associated with poor clinical outcome. We designed hybrid molecules, bearing the GABA molecule assembled with chemical fragments that interact with the serotonin 5-HT6 receptor. Such a combination aimed to curb neuroinflammation, remodel GABA-ergic signaling, and provide antidepressant-like activity. The most promising hybrid 3B exerted nanomolar affinity for 5-HT6 receptors and exerted agonistic properties on GABA-A receptors. Developability studies conferred that 3B exerted favorable drug-like properties and optimal brain penetration. In in vivo studies, 3B exerted robust antidepressant-like activity and proved to be highly effective in reducing levels of oxidative stress markers and the pro-inflammatory cytokine IL-6. The inetersting pharmacological profile of 3B makes it a promising candidate for further development for depression associated with neuroinflammation.


Assuntos
Depressão , Serotonina , Humanos , Depressão/tratamento farmacológico , Doenças Neuroinflamatórias , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ácido gama-Aminobutírico
20.
Cien Saude Colet ; 28(1): 83-92, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36629583

RESUMO

This article aims to assess the prevalence of psychotropic and antidepressant use and associated factors in a Brazilian Amazon city. Two cross-sectional studies conducted in Manaus in 2015 and 2019 with adults selected by probabilistic sampling. Prevalence ratios (PR) and 95% confidence intervals (95%CI) were calculated by Poisson regression with robust variance. 3,479 participants were included in 2015 and 2,321 in 2019; 2.0% used psychotropics in 2015 and 2.7% in 2019. Antidepressants were used by 0.4% (2015) and 1.4% (2019). Psychotropic use was lower in younger (PR = 0.41; 95%CI: 0.19-0.90), partnerless (PR = 0.64; 95%CI: 0.44-0.93), and informal workers (PR=0.47; 95%CI: 0.25-0.86), but higher in people with poor health (PR=2.86; 95%CI: 1.71-4.80), multimorbidity (PR = 3.24; 95%CI: 1.87-5.60), and who visited doctors (PR = 3.04; 95%CI: 1.45-6.38) or dentists (PR = 1.50; 95%CI: 1.08-2.10). Antidepressant use was higher in 2019 (PR = 2.90; 95%CI: 1.52-5.54), people with poor health (PR = 2.77; 95%CI: 1.16-6.62), and multimorbidity (PR = 8.72; 95%CI: 2.71-28.00), while lower in informal workers (PR = 0.33; 95%CI: 0.12-0.87) and unemployed (PR = 0.26; 95%CI: 0.08-0.81). Use of psychotropics remained stable in Manaus from 2015 to 2019, while antidepressant use more than tripled, which was marked by social inequalities.


Assuntos
Antidepressivos , Adulto , Humanos , Estudos Transversais , Brasil/epidemiologia , Prevalência , Fatores Socioeconômicos , Antidepressivos/uso terapêutico
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