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1.
Proc Natl Acad Sci U S A ; 117(38): 23484-23489, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32900924

RESUMO

While over 240,000 American students experienced a school shooting in the last two decades, little is known about the impacts of these events on the mental health of surviving youth. Using large-scale prescription data from 2006 to 2015, we examine the effects of 44 school shootings on youth antidepressant use. Our empirical strategy compares the number of antidepressant prescriptions written by providers practicing 0 to 5 miles from a school that experienced a shooting (treatment areas) to the number of prescriptions written by providers practicing 10 to 15 miles away (reference areas), both before and after the shooting. We include month-by-year and school-by-area fixed effects in all specifications, thereby controlling for overall trends in antidepressant use and all time-invariant differences across locations. We find that local exposure to fatal school shootings increases youth antidepressant use by 21.4% in the following 2 y. These effects are smaller in areas with a higher density of mental health providers who focus on behavioral, rather than pharmacological, interventions.


Assuntos
Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Exposição à Violência/psicologia , Saúde Mental/estatística & dados numéricos , Estudantes/psicologia , Adolescente , Saúde do Adolescente/estatística & dados numéricos , Adulto , Depressão/psicologia , Exposição à Violência/estatística & dados numéricos , Feminino , Humanos , Masculino , Instituições Acadêmicas/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Estados Unidos , Adulto Jovem
3.
Drugs Aging ; 37(9): 691-701, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32691329

RESUMO

BACKGROUND: According to previous studies, older patients frequently have serum concentrations of antidepressant medication above the recommended reference range. OBJECTIVE: The aim of this study was to investigate whether prescribed doses of antidepressants and the proportion of individuals with serum concentrations above the recommended reference range in older individuals (≥ 65 years) have changed over a 10-year period in Norway. METHODS: Serum concentration measurements and prescribed daily doses of antidepressants in 2007 and 2017 were extracted from a therapeutic drug monitoring (TDM) database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. The database contains routine follow-up serum concentration measurements of psychotropic drugs for patients from all parts of the country. For citalopram, escitalopram, sertraline, mirtazapine and venlafaxine, the differences between 2007 and 2017 in mean prescribed doses and the proportion of patients with at least one serum concentration above the reference range, according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guidelines, were compared. For the proportion of patients with serum concentrations above the recommended reference range, differences between individuals aged 65-79 and ≥ 80 years were also examined. RESULTS: The analyses of prescribed doses included 806 patients from 2007 and 1932 patients from 2017, with 972 and 2441 TDM samples, respectively. Between 2007 and 2017, modest reductions in prescribed daily doses were observed for citalopram (20 vs. 17 mg/day) and escitalopram (11 vs. 10 mg/day), but the proportion of patients with serum concentrations above the recommended reference range was unchanged for both drugs, i.e. 11.5% vs. 12.4% for citalopram and 3.6% vs. 2.9% for escitalopram. For mirtazapine and venlafaxine, prescribed doses were reduced from 28 to 25 mg/day and 150 to 125 mg/day, respectively. A significant reduction in the proportion of individuals with serum concentrations above the recommended reference range was observed for mirtazapine (27.1% vs. 11.5%) and for individuals aged ≥ 80 years using venlafaxine (60.0% vs. 30.0%). For sertraline, no differences in prescribed doses or serum concentrations above the recommended reference range were observed. CONCLUSIONS: Over a 10-year period, prescribed doses of antidepressants have been slightly reduced in older Norwegian patients, but a considerable proportion is still exposed to high serum concentrations of antidepressants.


Assuntos
Antidepressivos/administração & dosagem , Antidepressivos/sangue , Monitoramento de Medicamentos/tendências , Prescrições de Medicamentos/normas , Guias de Prática Clínica como Assunto/normas , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Bases de Dados Factuais , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/normas , Feminino , Humanos , Masculino , Noruega
4.
Life Sci ; 256: 117892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502538

RESUMO

BACKGROUND: Organophosphorus pesticides exert their toxic effects mainly by the inhibition of acetylcholinesterase (AChE), which is related to emotional disorders, such as depression. Atropine-oximes therapy is commonly used; however, the efficacy of oximes in the reactivation of AChE has been inconsistent. The objective of this study was to investigate the possible neuroprotective effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that combines the isatin and oxime functional groups, in rats exposed to malathion. The effect of Cℓ-HIN on the AChE activity and the BDNF-Trkß pathway in the prefrontal cortex of malathion-exposed rats were tested. METHODS: Wistar male rats were co-treated with Cℓ-HIN [50 mg/kg (p.o.) (3 mL/kg)] and/or malathion [250 mg/kg (i.p.) (5 mL/kg)] and performed behavioral tests twelve hours after these exposures. RESULTS: The Cℓ-HIN reversed the increased immobility time in the forced swimming test and the decreased grooming time in the splash test induced by malathion, but any significant difference was observed in locomotion analysis. These results demonstrate the antidepressant-like effect of Cℓ-HIN. The cortical AChE activity was reactivated by Cℓ-HIN in rats exposed to malathion. Malathion induced an increase in Trkß and a decrease in BDNF levels in the prefrontal cortex of rats, which were avoided by Cℓ-HIN. CONCLUSION: These findings support the hypothesis that Cℓ-HIN is an AChE reactivator with antidepressant-like properties, which is related to the improvement of BDNF-Trkß signaling after acute exposure to malathion in rats. Thus, the results allow suggesting the potential use of Cℓ-HIN as an oxime-based therapy against the neurotoxic effects of malathion.


Assuntos
Acetilcolinesterase/metabolismo , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Indóis/farmacologia , Malation/toxicidade , Oxindois/farmacologia , Receptor trkB/metabolismo , Transdução de Sinais , Animais , Antidepressivos/administração & dosagem , Antidepressivos/química , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Indóis/administração & dosagem , Indóis/química , Indóis/uso terapêutico , Masculino , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Oxindois/administração & dosagem , Oxindois/química , Oxindois/uso terapêutico , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
5.
Expert Opin Pharmacother ; 21(14): 1699-1711, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32543949

RESUMO

Introduction: A substantial number of patients with PD experience relapse after the discontinuation of effective pharmacotherapy, leading to detrimental effects on the individuals and considerable societal costs. This suggests the need to optimize pharmacotherapy to minimize relapse risk. Area covered: The present systematic review examines randomized, double-blind, placebo-controlled relapse prevention studies published over the last 20 years involving recommended medications. The authors aim to provide an overview of this topic and evaluate whether recent advances were achieved. Only seven studies were included, providing limited results. One-year maintenance pharmacotherapy with constant doses had protective effects against relapse in patients who had previously exhibited satisfactory responses to the same medication at the same doses. The duration of maintenance treatment did not influence relapse risk. No data were available concerning the use of lower doses or the predictors of relapse. Expert opinion: Relapse prevention in PD has received limited attention. Recent progress and conclusive indications are lacking. Rethinking pharmacological research in PD may be productive. Collecting a wide range of clinical and individual features/biomarkers in large-scale, multicenter long-term naturalistic studies, and implementing recent technological innovations (e.g., electronic medical records/'big data' platforms, wearable devices, and machine learning techniques) may help identify reliable predictive models.


Assuntos
Antidepressivos/uso terapêutico , Transtorno de Pânico/tratamento farmacológico , Prevenção Secundária/métodos , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/administração & dosagem , Esquema de Medicação , Humanos , Transtorno de Pânico/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/administração & dosagem , Resultado do Tratamento
6.
Expert Opin Pharmacother ; 21(14): 1685-1698, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32584616

RESUMO

Introduction: Postpartum depressive disorder (PPD) is a burdensome medical condition. To date, only one treatment (Brexanolone) has undergone registrational trials and is approved in the United States with an indication for the treatment of PPD. However, other treatments are prescribed and have been tested for this condition. Herein, the authors review the available scientific evidence pertaining to the somatic treatments of PPD. Areas covered: The authors evaluate the published open-label and randomized controlled trials (RCTs), examine the biological mechanisms of PPD treatments, and evaluate how the available data translates into information that may be useful for clinical practice. Expert opinion: Antidepressants have long been the mainstay of PPD treatment, despite the limited evidence from randomized clinical trials that supports this practice. Brexanolone improves treatment options for women with PPD. However, the relatively burdensome administration and monitoring protocol, along with the high cost of the medication, limit the possibility for an extensive use of this medication. Large, randomized, controlled trials of hormonal treatments in patients with PPD are warranted. Also, treatment with mood stabilizers and/or antipsychotics in women with major depressive disorder, who meet the DSM-5 mixed features specifiers in the post-partum period, should be tested in controlled clinical trials.


Assuntos
Antidepressivos/uso terapêutico , Depressão Pós-Parto/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Pregnanolona/uso terapêutico , beta-Ciclodextrinas/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Depressão Pós-Parto/metabolismo , Transtorno Depressivo Maior/metabolismo , Combinação de Medicamentos , Monitoramento de Medicamentos , Estrogênios/sangue , Feminino , Humanos , Ocitocina/sangue , Pregnanolona/administração & dosagem , Pregnanolona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Magnética Transcraniana , Resultado do Tratamento , Estados Unidos , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/efeitos adversos
7.
J Clin Psychiatry ; 81(4)2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32558401

RESUMO

OBJECTIVE: The aim of this systematic review and meta-analysis was to determine the effect of antidepressant discontinuation on the risk of relapse of depression during pregnancy. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and PsycInfo were searched from the inception of each database through March 2019 using keywords such as antidepressants, pregnancy, preconception, discontinuation, stop, recurrence, reintroduction, and relapse. STUDY SELECTION: Original studies that involved pregnant women who discontinued antidepressants during preconception (ie, 3 months prior to pregnancy) or pregnancy and examined the relapse of depression during pregnancy (ie, the reemergence of depression or reintroduction of medication) and published in English were included. A total of 2,172 records were identified, and the full texts of 37 articles were reviewed. Eight studies met the inclusion criteria, 6 of which fulfilled the quality criteria, with 4 studies providing data for the meta-analysis. DATA EXTRACTION: Data were extracted using a data extraction form developed for the purpose of this study. The Cochrane Collaboration Review Manager software version 5.3 was used to conduct the meta-analysis. RESULTS: Pooled data did not show higher risk of relapse of depression during pregnancy for women who discontinued antidepressants than for those who continued antidepressants (risk ratio [RR] = 1.74; 95% CI, 0.97 to 3.10; P = .06). In the subanalysis based on the severity and recurrence of depression in the study populations, the risk of relapse was significantly higher for populations suggestive of severe or recurrent depression (RR = 2.30; 95% CI, 1.58 to 3.35) but not for populations suggestive of mild or moderate depression severity (RR = 1.59; 95% CI, 0.83 to 3.04). CONCLUSIONS: Women with severe or recurrent depression should be informed about the increased risk of relapse following antidepressant discontinuation, and those who discontinue antidepressants should be monitored for relapse.


Assuntos
Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Suspensão de Tratamento , Antidepressivos/uso terapêutico , Feminino , Humanos , Gravidez , Recidiva
8.
Medicine (Baltimore) ; 99(22): e20185, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481383

RESUMO

The risk of colorectal cancer associated to antidepressant use remains unclear. The purpose of this meta-analysis was to investigate the risk of colorectal cancer associated to antidepressant use.Medline, Embase, Web of Science, and Cochrane Database were accessed from the dates of their establishment to October 2018, to collect study of antidepressant use and colorectal cancer morbidity and mortality. Then a meta-analysis was conducted using Stata 12.0 software.A total of 11 publications involving 109,506 participants were included. The meta-analysis showed that antidepressant use was not associated with colorectal cancer morbidity (relevant risk (RR): 0.97; 95% confidence interval (CI): 0.94-1.01) and mortality (RR: 1.08; 95% CI: 0.99-1.17). Subgroup analysis showed selective serotonin reuptake inhibitor (RR: 0.99; 95% CI: 0.96-1.03) or serotonin norepinephrine reuptake inhibitor (RR: 1.04; 95% CI: 0.86-1.26) were not associated with colorectal cancer risk; however, TCA was associated with colorectal cancer risk decrement (RR: 0.92; 95% CI: 0.87-0.98). Furthermore, the results also showed that antidepressant use was not associated with colorectal cancer risk in Europe and North America (RR: 0.97; 95% CI: 0.92-1.02) and Asia (RR: 1.00; 95% CI: 0.95-1.26). Additionally, a dose-response showed per 1 year of duration of antidepressant use incremental increase was not associated with colorectal cancer risk (RR: 0.96; 95% CI: 0.87-1.09).Evidence suggests that antidepressant use was not associated with colorectal cancer morbidity and mortality. The cumulative duration of antidepressant use did not utilized played critical roles.


Assuntos
Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Neoplasias Colorretais/epidemiologia , Transtorno Depressivo/tratamento farmacológico , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/psicologia , Relação Dose-Resposta a Droga , Humanos , Fatores de Risco , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos
9.
Psychopharmacology (Berl) ; 237(7): 2173-2185, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388621

RESUMO

RATIONALE: We have previously shown that in rats, capsaicin (Cap) has antidepressant-like properties when assessed using the forced swimming test (FST) and that a sub-threshold dose of amitriptyline potentiates the effects of Cap. However, synergistic antidepressant-like effects of the joint administration of Cap and the selective serotonin reuptake inhibitor citalopram (Cit) have not been reported. OBJECTIVES: To assess whether combined administration of Cap and Cit has synergistic effects in the FST and to determine whether this combination prevents the side effects of Cit. METHODS: Cap, Cit, and the co-administration of both substances were evaluated in a modified version of the FST (30-cm water depth) conducted in rats, as well as in the open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM). RESULTS: In line with previous studies, independent administration of Cap and Cit displayed antidepressant-like properties in the FST, while the combined injection had synergistic effects. In the OFT, neither treatment caused significant increments in locomotion. In the EPM, the time spent in the closed arms was lower in groups administered either only Cap or a combination of Cap and Cit than in groups treated with Cit alone. In the MWM, both Cap and the joint treatment (Cap and Cit) improved the working memory of rats in comparison with animals treated only with Cit. CONCLUSION: Combined administration of Cap and Cit produces a synergistic antidepressant-like effect in the FST and reduces the detrimental effects of Cit on anxiety and working memory.


Assuntos
Antidepressivos/administração & dosagem , Ansiedade/tratamento farmacológico , Capsaicina/administração & dosagem , Citalopram/administração & dosagem , Depressão/tratamento farmacológico , Memória de Curto Prazo/efeitos dos fármacos , Amitriptilina/uso terapêutico , Animais , Ansiedade/psicologia , Depressão/psicologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Memória de Curto Prazo/fisiologia , Ratos , Ratos Wistar , Inibidores de Captação de Serotonina/administração & dosagem , Natação/psicologia
10.
Psychopharmacology (Berl) ; 237(8): 2381-2394, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32435818

RESUMO

RATIONALE: Reward-related impairments are common in major depressive disorder (MDD) and may contribute to the loss of interest in pleasurable activities. A novel approach to studying reward-related decision-making are effort-based tasks; however, direct comparisons between delayed-onset and rapid-acting antidepressants (ADs) have not yet been carried out. OBJECTIVES: To investigate the effects of conventional delayed-onset ADs versus rapid-acting ADs, ketamine and scopolamine, on effort-related choice behaviour. METHODS: Female Lister hooded rats were trained in an operant effort for reward task (EfRT) where animals choose between working for a high value-high effort reward and consuming low value-low effort chow. Using a within-subject study design, animals were then tested following acute treatment with different monoaminergic ADs, and the rapid-acting ADs ketamine or scopolamine. RESULTS: Consistent with previous findings, we found choice behaviour was sensitive to dopaminergic manipulations. We observed that pre-feeding altered choice behaviour and that the use of high or low value reward differentially affected behaviour. Monoamine re-uptake inhibitors and rapid-acting ADs resulted in similar, general patterns of reduced motivation without any evidence for specific effects, and we did not observe any clear differences between these classes of antidepressant. CONCLUSIONS: Motivational changes induced by dopaminergic manipulations and pre-feeding differentially affect effort choice behaviour. However, both conventional delayed-onset ADs and ketamine and scopolamine appear to have detrimental effects on motivation in this task at the higher doses tested without any evidence of specificity for effort-related choice behaviour, in contrast to their specificity in tasks which look at more cognitive aspects of reward processing.


Assuntos
Antidepressivos/administração & dosagem , Comportamento de Escolha/efeitos dos fármacos , Motivação/efeitos dos fármacos , Recompensa , Animais , Comportamento de Escolha/fisiologia , Tomada de Decisões/efeitos dos fármacos , Tomada de Decisões/fisiologia , Preparações de Ação Retardada/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Motivação/fisiologia , Ratos , Fatores de Tempo
11.
J Clin Psychiatry ; 81(3)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32412697

RESUMO

​​​​ About 30%-50% of patients experience inadequate response to antidepressant therapy, and treatment choices for these patients include augmenting the antidepressant with another therapy, increasing the dose, switching to a different antidepressant, or combining antidepressants. Clinicians should tailor treatment strategies based on patients' response, tolerability, and disease severity. In this activity, augmentation and adjunctive strategies involving atypical antipsychotics, as well as off-label options including buspirone, stimulants, thyroid hormone, and lithium, are reviewed.​ ​.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/diagnóstico , Substituição de Medicamentos , Humanos , Escalas de Graduação Psiquiátrica , Falha de Tratamento
12.
J Clin Psychiatry ; 81(3)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32412700

RESUMO

OBJECTIVE: To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation. METHODS: This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria, active suicidal ideation with intent, and need for psychiatric hospitalization. Patients were randomized 1:1 to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care treatment (initial psychiatric hospitalization and newly initiated or optimized oral antidepressant[s] therapy). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score (primary endpoint) was analyzed using analysis of covariance (ANCOVA), and change in Clinical Global Impression of Severity of Suicidality Revised version (CGI-SS-r; key secondary endpoint) score was analyzed using ANCOVA on ranks with treatment difference estimated using the Hodges-Lehmann estimate. RESULTS: Greater improvement in MADRS total score was observed with esketamine + standard-of-care versus placebo + standard-of-care at 24 hours (least-squares mean difference [SE]: -3.8 [1.39]; 95% CI, -6.56 to -1.09; 2-sided P = .006), as well as at earlier (4 hours) and later time points during 4-week double-blind treatment. The difference between groups in the severity of suicidality was not statistically significant (median of treatment difference [95% CI]: 0.0 [-1.00 to 0.00]; 2-sided P = .107). The most common adverse events among esketamine-treated patients were dizziness, dissociation, headache, nausea, and somnolence. CONCLUSIONS: These findings demonstrate rapid and robust efficacy of esketamine nasal spray in reducing depressive symptoms in severely ill patients with major depressive disorder who have active suicidal ideation with intent. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03039192.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ketamina/uso terapêutico , Ideação Suicida , Administração Intranasal , Adolescente , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Feminino , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Adulto Jovem
13.
J Clin Psychiatry ; 81(4)2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32459407

RESUMO

OBJECTIVE: Esketamine, the S-enantiomer of ketamine, was recently approved as a rapid-acting intranasal therapy for depression and is currently under development for suicidality. The authors sought to determine the efficacy of adjunctive intranasal esketamine in major depressive disorder (MDD). DATA SOURCES: A systematic search of PubMed/MEDLINE was conducted up to January 2019, in addition to abstracts of major psychiatric meetings held since 2010. Searches were conducted by cross-referencing the term intranasal with the term esketamine. Where necessary, authors and/or study sponsors were contacted in order to obtain a copy of the presentation as well as any pertinent study details. STUDY SELECTION: 241 study abstracts were initially identified and reviewed. Selected studies were randomized, double-blind clinical trials comparing adjunctive intranasal esketamine to adjunctive placebo for MDD. DATA EXTRACTION: Data were extracted independently by two of the authors. A random effects model was used to calculate the standardized mean difference (SMD) between esketamine and placebo (intranasal saline) in the Montgomery-Asberg Depression Rating Scale (MADRS) score change from baseline to endpoint, serving as the primary outcome of the study. RESULTS: Five trials with 774 patients were pooled. Adjunctive esketamine was significantly more effective than placebo for MADRS score change, response, and remission (N = 774, SMD = 0.36, 95% CI = 0.24-0.49, P < .0001; response: risk ratio [RR] = 1.40, 95% CI = 1.22-1.61, P < .0001; remission: RR = 1.45, 95% CI = 1.20-1.75, P < .0001). Results remained statistically significant regardless of differences in the study sample, fixed vs new/optimized baseline antidepressants. CONCLUSIONS: Adjunctive intranasal esketamine for patients with MDD who are either treatment-resistant or acutely suicidal appears to be an effective treatment strategy.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Ketamina/uso terapêutico , Administração Intranasal , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Quimioterapia Combinada/métodos , Humanos , Ketamina/administração & dosagem , Resultado do Tratamento
14.
Medicine (Baltimore) ; 99(18): e19999, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358376

RESUMO

BACKGROUND: Depression is a common affective disorder characterized by marked and lasting melancholia, with corresponding thought and behavior changes. Due to an accelerated pace of life and increased work pressure, the incidence of depression has risen sharply, causing great harm to family and social life. Jiaotai pill (JTP) is a Chinese herbal formula that is commonly prescribed for depression and insomnia in clinical treatment, and exhibits antidepressant effects as shown in animal experimental research. However, there are no standard clinical trials to confirm its efficacy in treating depression. OBJECTIVE: This study aims to assess the efficacy and safety of JTP in the treatment of depression, so as to tap the clinical efficacy advantages of JTP and provide data support for its clinical application. METHODS: A randomized, multicenter clinical trial with parallel groups was designed in this study. A total of 40 patients with depression were included and randomly divided to either the treatment or the control group with a ratio of 1:1. The patients received JTP plus fluoxetine or fluoxetine alone once per day for 8 weeks. The primary outcome included the Hamilton Depression Rating Scale score for patients and brain structure and function by functional magnetic resonance imaging. The secondary outcomes included Traditional Chinese medicine syndrome integral scale scores, Wisconsin Card Sorting Test, blood metabonomics, urine metabonomics. CONCLUSION: The results of this trial will find changes in brain structure, brain function, and metabolism in patients with depression, and provide critical evidence for JTP in the treatment of depression.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adolescente , Adulto , Idoso , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Método Duplo-Cego , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Adulto Jovem
16.
Psiquiatr. biol. (Internet) ; 27(1): 9-15, ene.-abr. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-193255

RESUMO

Los trastornos depresivos representan la principal causa de discapacidad en el mundo, siendo una de las enfermedades que requieren mayor número de bajas laborales y costes asociados. Los antidepresivos pueden tardar incluso meses en lograr respuesta y remisión. De hecho, se estima que el 30% de pacientes con trastorno depresivo mayor son resistentes al tratamiento. Recientemente se ha aprobado la esketamina intranasal como tratamiento de este tipo de pacientes. El desarrollo de este medicamento incluye numerosos estudios que apoyan su seguridad a corto y largo plazo en pacientes con depresión resistente al tratamiento. Por ello, el objetivo del presente estudio es realizar una revisión sistemática de estudios de fase III con esketamina intranasal. Tras realizar una búsqueda en Medline en la que se obtuvieron 5 estudios, 3 a corto plazo y 2 a largo, el tratamiento de esketamina intranasal en combinación con un antidepresivo oral ha demostrado ser eficaz y seguro en pacientes con depresión resistente al tratamiento. Los resultados de seguridad fueron consistentes en todos los estudios sin presentar efectos adversos inesperados a largo plazo


Depressive disorders are the main cause of incapacity at a world level on being one of the illnesses that require a large number of days off work and associated costs. Antidepressants may even take months to achieve a response and remission. In fact, it is estimated that 30% of patients with a Major Depressive Disorder are resistant to the treatment. Intranasal eskatamine has recently been approved as treatment for this type of patient. The development of this drug includes numerous studies that support its safety in the short- and long-term in patients with Treatment-Resistant Depression. For this reason, the aim of the present article is to perform a systematic review of phase III studies with intranasal eskatamine. After carrying out a search on Medline, in which 5 studies were obtained. Three of them were short-term, and 2 long-term. The intranasal esketamine treatment in combination with an oral antidepressant was shown to be effective and safe in patients with treatment-resistant depression. The safety results were consistent in all the studies, without there being any unexpected adverse effects in the long-term


Assuntos
Humanos , Depressão/tratamento farmacológico , Administração Intranasal , Antidepressivos/administração & dosagem , Ketamina/administração & dosagem
17.
Nat Commun ; 11(1): 1635, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32242018

RESUMO

It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N = 424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress-induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behavior, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists have antidepressant-like effects and upregulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.


Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Receptores Acoplados a Proteínas-G/metabolismo , Adulto , Animais , Estudos de Coortes , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Feminino , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Receptores Acoplados a Proteínas-G/genética , Inibidores de Captação de Serotonina/administração & dosagem , Resultado do Tratamento
18.
J Clin Psychiatry ; 81(3)2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32316080

RESUMO

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase. RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]). CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Administração Intranasal , Administração Oral , Adolescente , Adulto , Idoso , Antidepressivos/administração & dosagem , Cognição/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Adulto Jovem
19.
Life Sci ; 252: 117669, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298740

RESUMO

Chronic social defeat stress (CSDS) is an ethologically relevant psychosocial stress animal model and has been widely used in depression studies. Ginsenoside Rg1 (Rg1) is the major active ingredients of ginseng with low toxicity and neuroprotective effects. The present study aims to investigate the antidepressant effects of Rg1 in CSDS mice and explore its molecular mechanism. We found that Rg1 (20 or 40 mg/kg, i.g.) administration significantly alleviated depressive-like behaviors caused by 4-week CSDS exposure, as measured by social interaction test and sucrose preference test, tail suspension test and forced swim test. Additionally, Rg1 treatment inhibited CSDS-induced production of IL-6, TNF-α and IL-1ß, decreased the expression of iNOS, COX2, and caspase-9 and -3, and inhibited microglial activation (Iba1) in the hippocampus. Rg1 was found to significantly downregulate p-JNK1/2 and p-P38 MAPK levels, upregulate p-ERK1/2 levels and inhibit the expression of phosphorylated NF-κB in the hippocampus. Meanwhile, Rg1 regulated SIRT1 and decreased the levels of acetylated p65 (ac-p65) in the hippocampus. Moreover, the reduction in adult hippocampal neurogenesis in CSDS mice was reversed by Rg1 treatment. In conclusion, our findings suggest that Rg1 prevents depressive-like behavior in CSDS-exposed mice, partially through the downregulation of hippocampal neuroinflammation and the upregulation of adult hippocampal neurogenesis and that these changes presumably occur through increased anti-inflammatory effects and the inhibition of proinflammatory cytokine and neurotoxic mediator expression and microglial activation, which is partly mediated by the regulation of the MAPK and SIRT1 signaling pathways and results in the inhibition of NF-κB transcriptional activity.


Assuntos
Antidepressivos/farmacologia , Depressão/prevenção & controle , Ginsenosídeos/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ginsenosídeos/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Neurogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
20.
Rev Saude Publica ; 54: 40, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294666

RESUMO

OBJECTIVE: In recent decades there has been an increase in the use of antidepressants (AD) and a decrease in the use of benzodiazepines (BDZ). Prevalence, cumulative incidence, and factors associated with the incidence of AD and BDZ use in a Brazilian population were estimated in this article. METHODS: Data were collected with a self-administered questionnaire in a cohort of employees from a university in Rio de Janeiro. The prevalence of the use of AD and BDZ was calculated for 1999 (4,030), 2001 (3,574), 2006-07 (3,058), and 2012 (2,933). The cumulative incidences of the use of AD and BDZ between 1999 and 2007 were estimated by the Poisson models with robust variance estimates. RESULTS: In 1999, the prevalence of the use of AD and BDZ were 1.4% (95%CI: 1.1-1.8) and 4.7% (95%CI: 4.1-5.4), respectively; in 2012, they were 5.4% (95%CI: 5.5-6.2) and 6.8% (95%CI: 6.0-7.8). The incidence of use, between 1999 and 2007, was 4.9% (95%CI: 4.2-5.7) for AD and 8.3% (95%CI: 7.3-9.3) for BDZ. The incidences of AD and BDZ use were higher among women and participants with a positive General Health Questionnaire. CONCLUSION: In this population, the increase in the use of AD was not accompanied by a decrease in the use of BDZ, showing the prescriptions for psychotropic medication do not follow the currently recommended guidelines for treatment of common mental health disorders.


Assuntos
Antidepressivos/administração & dosagem , Benzodiazepinas/administração & dosagem , Uso de Medicamentos/tendências , Adulto , Fatores Etários , Brasil , Estudos de Coortes , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicotrópicos , Fatores Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
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