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2.
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
4.
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
5.
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
6.
Ecotoxicol Environ Saf ; 250: 114493, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36608562

RESUMO

Antidepressant prescriptions are on a rise worldwide and this increases the concerns for the impacts of these pharmaceuticals on nontarget organisms. Antidepressants are neuroactive compounds that can affect organism's behavior. Behavior is a sensitive endpoint that may also propagate effects at a population level. Another interesting aspect of antidepressants is that they have shown to induce non-monotonic dose-response (NMDR) curves. While such NMDR relationships may have clear implications for the environmental risk, the resolution of current studies is often too coarse to be able to detect relevant NMDR. Therefore, the current study was performed into the behavioral effects (activity, feeding and chemotaxis) in Caenorhabditis elegans as the model organism of the selective serotonin reuptake inhibitors fluoxetine and sertraline and the acetylcholinesterase inhibiting pesticide chlorpyrifos, using a wide range of concentrations (ng/l to mg/l). In order to statistically examine the non-monotonicity, nonlinear regression models were applied to the results. The results showed a triphasic dose-response relationship for activity and chemotaxis after exposure to fluoxetine, but not to sertraline or chlorpyrifos. Effects of fluoxetine already occurred at low concentrations in the range of ng/l while sertraline only showed effects at concentrations in the µg/l range, similar to chlorpyrifos. The different responses between fluoxetine and sertraline, both SSRIs, indicate that response patterns may not always be extrapolated from chemicals with the same primary mode of action. The effects of fluoxetine at low concentrations, in a non-monotonic manner, confirm the relevance of examining such responses at low concentrations.


Assuntos
Clorpirifos , Fluoxetina , Animais , Fluoxetina/toxicidade , Sertralina/toxicidade , Caenorhabditis elegans , Acetilcolinesterase , Antidepressivos/toxicidade , /toxicidade
7.
Phytomedicine ; 109: 154558, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610123

RESUMO

BACKGROUND: Depression is one of the most debilitating and severe psychiatric disorders and a serious public health concern. Currently, many treatments are indicated for depression, including traditional Chinese medicinal formulae such as Xiao-Yao-San (XYS), which has effective antidepressant effects in clinical and animal studies. PURPOSE: To summarize current evidence of XYS in terms of the preclinical and clinical studies and to identify the multi-level, multi-approach, and multi-target potential antidepressant mechanisms of XYS and active components of XYS by a comprehensive search of the related electronic databases. METHODS: The following electronic databases were searched from the beginning to April 2022: PubMed, MEDLINE, Web of Science, Google Scholar, and China National Knowledge Infrastructure. RESULTS: This review summarizes the antidepressant mechanisms of XYS and its active ingredients, which are reportedly correlated with monoamine neurotransmitter regulation, synaptic plasticity, and hypothalamic-pituitary-adrenal axis, etc. CONCLUSION: XYS plays a critical role in the treatment of depression by the regulation of several factors, including the monoaminergic systems, hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brain-derived neurotrophic factor levels, brain-gut axis, and other pathways. However, more clinical and animal studies should be conducted to further investigate the antidepressant function of XYS and provide more evidence and recommendations for its clinical application. Our review provides an overview of XYS and guidance for future research direction.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/psicologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Humanos
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.
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
13.
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
14.
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
15.
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
16.
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
17.
J Clin Psychiatry ; 84(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630648

RESUMO

Objective: To determine the extent that treatment with transcranial magnetic stimulation (TMS) in diverse clinical settings has anxiolytic and antidepressant effects in patients with major depressive disorder (MDD) and moderate-to-severe anxiety symptoms and to contrast anxious and nonanxious depression subgroups in antidepressant effects.Methods: Within the NeuroStar Advanced Therapy System Clinical Outcomes Registry, 1,820 patients were identified with a diagnosis of MDD (using ICD-9, ICD-10, or DSM-IV) who completed the Patient Health Questionnaire-9 (PHQ-9) and Global Anxiety Disoder-7 scale (GAD-7) at baseline and following at least 1 TMS treatment between May 2016 and January 2021. Anxious depression was defined as a baseline GAD-7 score of 10 or greater (n = 1,514) and nonanxious depression by GAD-7 scores below this threshold (n = 306). Intent-to-treat and Completer samples were defined for patients treated with any TMS protocol and for the subgroup treated only with high-frequency left dorsolateral prefrontal cortex stimulation.Results: Patients with anxious depression showed clinically meaningful anxiolytic and antidepressant effects, averaging approximately 50% or greater reductions in both GAD-7 and PHQ-9 scores following TMS in all samples. The anxious and nonanxious depression groups had equivalent absolute improvement in PHQ-9 scores (P values ≥ .29). However, the anxious group had higher scores both at baseline and following TMS resulting in significantly lower categorical rates of response (P values < .02) and remission (P values < .001) in depressive symptoms. Among those with anxious depression, the change in anxiety and depression symptoms strongly covaried (r1512 = 0.75, P < .001).Conclusions: Routine TMS delivered in diverse clinical settings results in marked anxiolytic and antidepressant effects in patients with anxious depression. The extent of improvement in anxiety and depression symptoms strongly covaries.


Assuntos
Ansiolíticos , Transtorno Depressivo Maior , Humanos , Depressão , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico , Estimulação Magnética Transcraniana , Resultado do Tratamento , Antidepressivos/uso terapêutico
18.
BMC Public Health ; 23(1): 85, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631810

RESUMO

BACKGROUND: Population-based research examining geographic variability in psychotropic medication dispensing to children and youth and the sociodemographic correlates of such variation is lacking. Variation in psychotropic use could reflect disparities in access to non-pharmacologic interventions and identify potentially concerning use patterns. METHODS: We conducted a population-based study of all Ontario residents aged 0 to 24 years who were dispensed a benzodiazepine, stimulant, antipsychotic or antidepressant between January 1, 2018, and December 31, 2018. We conducted small-area variation analyses and identified determinants of dispensing using negative binomial generalized estimating equation models. RESULTS: The age- and sex-standardized rate of psychotropic dispensing to children and youth was 76.8 (range 41.7 to 144.4) prescriptions per 1000 population, with large variation in psychotropic dispensing across Ontario's census divisions. Males had higher antipsychotic [rate ratio (RR) 1.40; 95% confidence interval (CI) 1.36 to 1.44) and stimulant (RR 1.75; 95% CI 1.70 to 1.80) dispensing rates relative to females, with less use of benzodiazepines (RR 0.85; 95% CI 0.83 to 0.88) and antidepressants (RR 0.81; 95% CI 0.80 to 0.82). Lower antipsychotic dispensing was observed in the highest income neighbourhoods (RR 0.72; 95% CI 0.70 to 0.75) relative to the lowest. Benzodiazepine (RR 1.12; 95% CI 1.01 to 1.24) and stimulant (RR 1.11; 95% CI 1.01 to 1.23) dispensing increased with the density of mental health services in census divisions, whereas antipsychotic use decreased (RR 0.82; 95% CI 0.73 to 0.91). The regional density of child and adolescent psychiatrists and developmental pediatricians (RR 1.00; 95% CI 0.99 to 1.01) was not associated with psychotropic dispensing. CONCLUSION: We found significant variation in psychotropic dispensing among young Ontarians. Targeted investment in regions with long wait times for publicly-funded non-pharmacological interventions and novel collaborative service models may minimize variability and promote best practices in using psychotropics among children and youth.


Assuntos
Antipsicóticos , Masculino , Feminino , Humanos , Criança , Adolescente , Antipsicóticos/uso terapêutico , Ontário , Psicotrópicos/uso terapêutico , Antidepressivos/uso terapêutico , Prescrições de Medicamentos , Benzodiazepinas/uso terapêutico , Projetos de Pesquisa
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.
Am J Clin Hypn ; 65(3): 223-240, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36638223

RESUMO

When it comes to antidepressant medications - popular, backbone drugs of modern psychiatry - even learned scholars and savvy clinicians find it difficult to separate honest, rigorous research from that which thrives on hidden agendas and ulterior motives. Fortunately, a mounting corpus of data-based studies, mostly meta-analyses, casts new and critical light on the clinical efficacy, side effects, and therapeutic outcomes of antidepressants. Spearheading these efforts over the past few decades, Irving Kirsch and colleagues have challenged the hegemonic view of antidepressants as an effective therapeutic intervention. Notably, Kirsch illuminates the small difference between antidepressants and placebos in mitigating depression-a difference that may be statistically significant yet fails to reach clinical significance. This piece sketches the important contributions Kirsch has made to the scientific understanding of antidepressant medications.


Assuntos
Hipnose , Psiquiatria , Humanos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Resultado do Tratamento , Depressão
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