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1.
Braz J Biol ; 83: e246194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468514

RESUMO

Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.


Assuntos
Anticonvulsivantes , Transtorno Depressivo Maior , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Encéfalo , Transtorno Depressivo Maior/tratamento farmacológico , Succinato de Desvenlafaxina/farmacologia , Camundongos , Estresse Oxidativo
2.
Trials ; 22(1): 585, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479619

RESUMO

BACKGROUND: Major depressive disorder is the second leading cause of years lost to disability worldwide. Anyu Peibo Capsule has been shown to be effective and safe in phase II trials. METHODS: This clinical study is a multi-center, randomized, double-blinded, placebo-controlled, parallel-group, phase III trial of Anyu Peibo Capsule in China. The aim is to test whether the administration of Anyu Peibo Capsule compared to placebo improves clinical outcomes in adults (aged 18 to 65 years) with MDD. Patients will receive an 8-week treatment of Anyu Peibo Capsule 1.6 g per day or placebo. The primary outcome will be the change from baseline in the total score for the Montgomery-Asberg Depression Rating Scale at the end of the 8-week treatment. DISCUSSION: The trial aims to provide pivotal evidence for the efficacy and safety of Anyu Peibo Capsule in patients with major depressive disorder. TRIAL REGISTRATION: ClinicalTrials.gov NCT04210973 . Registered on December 26, 2019.


Assuntos
Transtorno Depressivo Maior , Adulto , China , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
3.
J Psychosoc Nurs Ment Health Serv ; 59(9): 7-11, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34459676

RESUMO

Approximately 30% of people treated for a major depressive episode will not achieve remission after two or more treatment trials of first-line antidepressants and are considered to have treatment-resistant depression (TRD). Because the odds of remission decrease with every subsequent medication trial, it is important for clinicians to understand the characteristics and risk factors for TRD, subtypes of major depressive disorder that are more likely to be less responsive to first-line anti-depressants, and the available treatment options. In the current article, we review the approved treatments for TRD, including esketamine, and the evidence for psilocybin and pramipexole. Although limited in specificity, guidelines to help prescribers identify person-centered treatments for TRD are available. [Journal of Psychosocial Nursing and Mental Health Services, 59(9), 7-11.].


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Antidepressivos/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Quimioterapia Combinada , Humanos
4.
Syst Rev ; 10(1): 227, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389045

RESUMO

BACKGROUND: Major depressive disorder is a common psychiatric disorder causing great burden on patients and societies. Tricyclic antidepressants are frequently used worldwide to treat patients with major depressive disorder. It has repeatedly been shown that tricyclic antidepressants reduce depressive symptoms with a statistically significant effect, but the effect is small and of questionable clinical importance. Moreover, the beneficial and harmful effects of all types of tricyclic antidepressants have not previously been systematically assessed. Therefore, we aim to investigate the beneficial and harmful effects of tricyclic antidepressants versus 'active placebo', placebo or no intervention for adults with major depressive disorder. METHODS: This is a protocol for a systematic review with meta-analysis that will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, bias will be assessed with the Cochrane Risk of Bias tool-version 2, our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control random errors and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases and trial registers, such as CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov from their inception to 12 May 2021. Clinical study reports will be applied for from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results from the literature searches, extract data and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing tricyclic antidepressants with 'active placebo', placebo or no intervention for adults with major depressive disorder. The following interventions will be assessed: amineptine, amitriptyline, amoxapine, butriptyline, cianopramine, clomipramine, desipramine, demexiptiline, dibenzepin, dosulepin, dothiepin, doxepin, imipramine, iprindole, lofepramine, maprotiline, melitracen, metapramine, nortriptyline, noxiptiline, opipramol, protriptyline, tianeptine, trimipramine and quinupramine. Primary outcomes will be depressive symptoms, serious adverse events and quality of life. Secondary outcomes will be suicide or suicide-attempts and non-serious adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses. DISCUSSION: Tricyclic antidepressants are recommended by clinical guidelines and frequently used worldwide in the treatment of major depressive disorder. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021226161 .


Assuntos
Transtorno Depressivo Maior , Adulto , Antidepressivos Tricíclicos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Metanálise como Assunto , Qualidade de Vida , Literatura de Revisão como Assunto
5.
Expert Opin Pharmacother ; 22(13): 1651-1660, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34404290

RESUMO

Introduction: Pimavanserin is FDA-approved to treat hallucinations and delusions associated with Parkinson's disease psychosis. As a potent 5-HT2A inverse agonist/antagonist, it could be efficacious in other psychiatric disorders. Recently, several studies have investigated this potential.Areas covered: The authors review the efficacy and adverse effects of pimavanserin for hallucinations in dementia, major depression, and schizophrenia.Expert opinion: Two controlled studies suggest pimavanserin has potential as a treatment for hallucinations in dementia. In patients with depression who did not respond to antidepressant treatment, pimavanserin augmentation was efficacious in a phase 2 study. Pimavanserin augmentation also alleviated sexual side effects of SSRI and SSNI. However, Acadia Pharmaceuticals stated in a press release that it does not plan further antidepressant trials based on its phase 3 trial, which showed a nonsignificant trend toward an antidepressant effect. Since almost all existing antipsychotics fail to substantially benefit negative symptoms, better treatments are needed. Pimavanserin augmentation of antipsychotics did benefit negative symptoms (effect size≈0.2) but failed to reduce the total PANSS score significantly in two large, well-controlled double-blind studies. Pimavanserin has a good safety profile.


Assuntos
Antipsicóticos , Transtorno Depressivo Maior , Transtornos Psicóticos , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Ureia/análogos & derivados , Ureia/uso terapêutico
6.
Adv Ther ; 38(9): 4900-4916, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34368919

RESUMO

INTRODUCTION: Pre-existing conditions relevant for adverse events (AE) and the potential for drug-drug interactions (DDIs) may limit safe pharmacotherapeutic augmentation options for patients with major depressive disorder (MDD). This concern may be heightened among patients with treatment-resistant depression (TRD), who often have comorbid medical disorders. METHODS: Adults with MDD and ≥ 1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases. Those initiating a new regimen after two regimens at adequate dose and duration were considered to have TRD. The index date was defined at TRD onset or on a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions 12 months pre-index and potential DDIs 3 months pre/post-index associated with specific non-antidepressant augmentation therapies, including atypical antipsychotics (APs), buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts. RESULTS: Overall, 3414 patients with TRD and non-TRD MDD (mean age 39.7 years, 69% female) were matched. Relative to non-TRD MDD, patients with TRD had 33% higher likelihood of ≥ 1 pre-existing condition relevant for AEs listed in product labels of non-antidepressant augmentation therapies (p < 0.001). Patients with TRD vs. non-TRD MDD had 12.9 and 6.4 times higher likelihood of ≥ 2 and ≥ 3 DDIs, respectively, based on their medication regimen (all p < 0.001). CONCLUSION: Pre-existing conditions relevant for listed AEs and potential DDIs limit safe augmentation options in MDD, particularly among patients with TRD. Payer prior authorization policies requiring several augmentation therapy trials to access novel treatments may complicate clinical management of this population.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Preparações Farmacêuticas , Adulto , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Interações Medicamentosas , Feminino , Humanos , Masculino , Cobertura de Condição Pré-Existente , Prevalência , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 100(29): e26769, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398056

RESUMO

ABSTRACT: There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety and tolerability concerns arise regarding adverse drug reactions and specific subpopulations. This paper aims to investigate the relationship between dissociative and psychometric measures in course of intravenous ketamine treatment in TRD inpatients with major depressive disorder and bipolar disorder.This study result represents safety data in a population of 49 inpatients with major depressive disorder and bipolar disorder subjects receiving eight 0.5 mg/kg of ketamine intravenous infusions, with a duration of 40 min each, as an add-on treatment to standard-of-care pharmacotherapy, registered in the naturalistic observational protocol of the tertiary reference unit for mood disorders (NCT04226963). The safety psychometrics assessed dissociation and psychomimetic symptomatology with the Clinician-Administered Dissociative States Scale (CADSS) the Brief Psychiatric Rating Scale (BPRS).The significant differences in CADSS scores between measurements in course of the treatment were observed (P = .003). No significant differences between BPRS measurements were made after infusions. In each case, both BPRS and CADSS values dropped to the "absent" level within 1 hour from the infusion. Neither CADSS nor BPRS scores were associated with the treatment outcome.The study demonstrates a good safety profile of intravenous ketamine as an add-on intervention to current psychotropic medication in TRD. The abatement of dissociation was observed in time with no sequelae nor harm. The study provides no support for the association between dissociation and treatment outcome.This study may be underpowered due to the small sample size. The protocol was defined as a study on acute depressive symptomatology without blinding.


Assuntos
Anestésicos Dissociativos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Administração Intravenosa , Adolescente , Adulto , Idoso , Anestésicos Dissociativos/administração & dosagem , Transtornos Dissociativos , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
8.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360959

RESUMO

BACKGROUND: Rates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD. METHODS: Rats housed at 4500 ft were given dietary creatine monohydrate (CRMH, 4% w/w, 5 weeks) vs. un-supplemented diet, and impact on depression-like behavior, brain bioenergetics, serotonin and SSRI efficacy assessed. RESULTS: CRMH significantly improved brain creatine in a sex-based manner. At altitude, CRMH increased serotonin levels in the female prefrontal cortex and striatum but reduced male striatal and hippocampal serotonin. Dietary CRMH was antidepressant in the forced swim test and anti-anhedonic in the sucrose preference test in only females at altitude, with motor behavior unchanged. CRMH improved fluoxetine efficacy (20 mg/kg) in only males at altitude: CRMH + SSRI significantly improved male striatal creatine and serotonin vs. CRMH alone. CONCLUSIONS: Dietary CRMH exhibits sex-based efficacy in resolving altitude-related deficits in brain biomarkers, depression-like behavior and SSRI efficacy, and may be effective clinically for SSRI-resistant depression at altitude. This is the first study to link CRMH treatment to improving brain serotonin.


Assuntos
Encéfalo/efeitos dos fármacos , Creatina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Serotonina/metabolismo , Animais , Encéfalo/metabolismo , Creatina/administração & dosagem , Creatina/farmacologia , Suplementos Nutricionais , Sinergismo Farmacológico , Metabolismo Energético , Feminino , Fluoxetina/administração & dosagem , Fluoxetina/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/farmacologia , Fatores Sexuais
9.
Artigo em Russo | MEDLINE | ID: mdl-34283536

RESUMO

The article presents the literature data that determine the place of antidepressants in the relief and maintenance therapy for recurrent depression (RD) and depression in the framework of bipolar affective disorder (BPAD) and provides a justification for their use in the presence of residual depressive symptoms during remission. There are several ways to achieve complete remission: determination of the nature of residual symptoms; identification of adverse side-effects that have occurred as a result of the therapy; the establishment of those symptoms that are subjectively perceived by the patient as interfering with his/her full life. The data on the effective use of agomelatin for maintenance therapy, both as monotherapy and in combination with other antidepressants, anticonvulsants and neuroleptics, in RD and BPAD are presented. The authors have analyzed the case histories of 29 outpatients with depressions of various origins (RDD, BPAD, prolonged psychogenic depression, organic affective disorder), who received agomelatin as part of complex and monotherapy for a long time (1 to 13 years), and justified the predictors of its efficacy.


Assuntos
Antipsicóticos , Transtorno Bipolar , Transtorno Depressivo Maior , Transtornos Psicóticos , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Masculino , Transtornos Psicóticos/tratamento farmacológico
10.
Artigo em Russo | MEDLINE | ID: mdl-34283542

RESUMO

The review briefly summarizes experimental and preclinical data of the role of pro-inflammatory cytokines in triggering pathophysiological changes associated with depression, primarily major depressive disorder (MDD), as well as the possibility of using anti-inflammatory drugs as antidepressants.


Assuntos
Transtorno Depressivo Maior , Preparações Farmacêuticas , Anti-Inflamatórios/uso terapêutico , Antidepressivos/uso terapêutico , Citocinas , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos
11.
J Affect Disord ; 293: 429-434, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34246952

RESUMO

BACKGROUND: Inflammatory mechanisms are believed to contribute to the manifestation of major depressive disorder (MDD). Central cholinergic activity may moderate this effect. Here, we tested if volume of the cholinergic basal forebrain is associated with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglial activation in people with late life MDD. METHODS: Basal forebrain volume was determined from structural MRI scans and levels of CSF sTREM2 with immunoassay in 29 people with late-life MDD and 20 healthy older controls at baseline and 3 years follow-up. Associations were determined using Bayesian analysis of covariance. RESULTS: We found moderate level of evidence for an association of lower CSF levels of sTREM2 at 3 years follow up with MDD (Bayes factor in favor of an effect = 7.9). This level of evidence prevailed when controlling for overall antidepressant treatment and CSF levels of markers of AD pathology, i.e., Aß42/Aß40, ptau181 and total tau. Evidence was in favor of absence of an effect for baseline levels of CSF sTREM2 in MDD cases and for baseline and follow up data in controls. LIMITATIONS: The sample size of repeated CSF examinations was relatively small. Therefore, we used Bayesian sequential analysis to assess if effects were affected by sample size. Still, the number of cases was too small to stratify effects for different antidepressive treatments. CONCLUSIONS: Our data agree with the assumption that central cholinergic system integrity may contribute to regulation of microglia activity in late-life MDD.


Assuntos
Prosencéfalo Basal , Transtorno Depressivo Maior , Glicoproteínas de Membrana/líquido cefalorraquidiano , Peptídeos beta-Amiloides , Teorema de Bayes , Biomarcadores , Colinérgicos , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Microglia , Receptores Imunológicos
12.
J Psychiatr Res ; 141: 167-175, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34216945

RESUMO

Despite plenty of effective antidepressant (AD) treatments, the outcome of major depressive disorder (MDD) is often unsatisfactory, probably due to improvable exploitation of available therapies. This European, cross-sectional, naturalistic multicenter study investigated the frequency of additional psychotherapy in terms of a manual-driven psychotherapy (MDP) in 1410 adult in- and outpatients with MDD, who were primarily treated with AD psychopharmacotherapy. Socio-demographic and clinical patterns were compared between patients receiving both treatments and those lacking concomitant MDP. In a total of 1279 MDD patients (90.7%) with known status of additional MDP, those undergoing a psychopharmacotherapy-MDP combination (31.2%) were younger, higher educated, more often employed and less severely ill with lower odds for suicidality as compared to patients receiving exclusively psychopharmacotherapy (68.8%). They experienced an earlier mean age of MDD onset, melancholic features, comorbid asthma and migraine and received lower daily doses of their first-line ADs. While agomelatine was more often established in these patients, MDD patients without MDP received selective serotonin reuptake inhibitors more frequently. These two patient groups did not differ in terms of response, non-response and treatment resistant depression (TRD). Accordingly, the employment of additional MDP could not be related to better treatment outcomes in MDD. The fact that MDP was applied in a minority of patients with rather beneficial socio-demographic and clinical characteristics might reflect inferior accessibility of these psychotherapeutic techniques for socially and economically disadvantaged populations.


Assuntos
Transtorno Depressivo Maior , Adulto , Estudos Transversais , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Psicoterapia , Resultado do Tratamento
14.
Transl Psychiatry ; 11(1): 381, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238923

RESUMO

Major depressive disorder (MDD) is complex and multifactorial, posing a major challenge of tailoring the optimal medication for each patient. Current practice for MDD treatment mainly relies on trial and error, with an estimated 42-53% response rates for antidepressant use. Here, we sought to generate an accurate predictor of response to a panel of antidepressants and optimize treatment selection using a data-driven approach analyzing combinations of genetic, clinical, and demographic factors. We analyzed the response patterns of patients to three antidepressant medications in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, and employed state-of-the-art machine learning (ML) tools to generate a predictive algorithm. To validate our results, we assessed the algorithm's capacity to predict individualized antidepressant responses on a separate set of 530 patients in STAR*D, consisting of 271 patients in a validation set and 259 patients in the final test set. This assessment yielded an average balanced accuracy rate of 72.3% (SD 8.1) and 70.1% (SD 6.8) across the different medications in the validation and test set, respectively (p < 0.01 for all models). To further validate our design scheme, we obtained data from the Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) of patients treated with citalopram, and applied the algorithm's citalopram model. This external validation yielded highly similar results for STAR*D and PGRN-AMPS test sets, with a balanced accuracy of 60.5% and 61.3%, respectively (both p's < 0.01). These findings support the feasibility of using ML algorithms applied to large datasets with genetic, clinical, and demographic features to improve accuracy in antidepressant prescription.


Assuntos
Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Demografia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Humanos , Aprendizado de Máquina , Resultado do Tratamento
15.
BMJ Open ; 11(7): e049331, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244279

RESUMO

INTRODUCTION: Major depressive disorder (MDD) affects more than 264 million people worldwide and is associated with an impaired quality of life as well as a higher risk of mortality. Current routine treatments demonstrate limited effectiveness. Light therapy (LT) on its own or in combination with antidepressant treatments could be an effective treatment, but the use of conventional LT devices use is restrictive. Portable LT devices allow patients to continue with their day-to-day activities and therefore encourage better treatment compliance. They have not been evaluated in MDD. METHODS AND ANALYSIS: The study is a single-centre, double-blind, randomised controlled trial assessing the efficacy of LT delivered via a portable device in addition to usual care (medical care and drug treatment) for inpatients and outpatients with unipolar non-seasonal MDD. Over the course of 8 weeks, patients use the device daily for 30 min at medium intensity as soon as possible after waking up and preferably between 07:00 and 09:00. All patients continue their usual care with their referring physician. N=50 patients with MDD are included. The primary outcome measure is depressive symptom severity assessed using the Montgomery-Åsberg Depression Rating Scale between baseline and the eighth week. Secondary outcome measures are sleep quality assessed using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale and anxiety level assessed on the Hamilton Anxiety Rating Scale, between baseline and week 8. Further parameters relating to cognitive function are measured at baseline and after the intervention. An ancillary study aims to evaluate the impact of MDD on the retina and to follow its progression. Main limitations include risk of discontinuation or non-adherence and bias in patient selection. ETHICS AND DISSEMINATION: The study protocol was approved by Ile de France X's Ethics Committee (protocol number 34-2018). Findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03685942.


Assuntos
Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , França , Humanos , Fototerapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
16.
Neurosci Biobehav Rev ; 128: 693-708, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34265321

RESUMO

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) treat dyslipidaemia and cardiovascular disease by inhibiting cholesterol biosynthesis. They also have immunomodulatory and anti-inflammatory properties. Beyond cardiovascular disease, cholesterol and inflammation appear to be components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Statins may therefore afford some therapeutic benefit in mood disorders. In this paper, we review the pathophysiology of mood disorders with a focus on pharmacologically relevant pathways, using major depressive disorder and bipolar disorder as exemplars. Statins are discussed in the context of these disorders, with particular focus on the putative mechanisms involved in their anti-inflammatory and immunomodulatory effects. Recent clinical data suggest that statins may have antidepressant properties, however given their interactions with many known biological pathways, it has not been fully elucidated which of these are the major determinants of clinical outcomes in mood disorders. Moreover, it remains unclear what the appropriate dose, or appropriate patient phenotype for adjunctive treatment may be. High quality randomised control trials in concert with complementary biological investigations are needed if the potential clinical effects of statins on mood disorders, as well as their biological correlates, are to be better understood.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Inibidores de Hidroximetilglutaril-CoA Redutases , Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Transtornos do Humor/tratamento farmacológico
17.
Asian J Psychiatr ; 63: 102744, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34325252

RESUMO

BACKGROUND: Monopharmacy with antipsychotics and antidepressants is the first-line treatment for schizophrenia and major depressive disorder (MDD) in most clinical guidelines, while polypharmacy with psychotropic agents in the treatment of schizophrenia is common in clinical practice. There are no detailed data on the prescription patterns for inpatients with mental illness with reliable diagnoses made by treating psychiatrists. METHODS: We gathered prescription data at discharge from 2177 patients with schizophrenia and 1238 patients with MDD from October 2016 to March 2018. RESULTS: The patients with schizophrenia aged between 60 and 79 were prescribed lower doses of antipsychotics and hypnotics/anxiolytics than those aged between 40 and 59. There were significant differences between the prescription rate of antipsychotics in the patients with schizophrenia and that of antidepressants in the patients with MDD. The frequency of concomitant drugs such as anti-Parkinson drugs, anxiolytics/hypnotics and mood stabilizers in the subjects with schizophrenia prescribed antipsychotic polypharmacy was significantly higher than that with monotherapy. For the patients with schizophrenia, olanzapine, risperidone, aripiprazole, quetiapine, and blonanserin were the five most prescribed antipsychotics. For the patients with MDD, mirtazapine, duloxetine, escitalopram, trazodone and sertraline were the five most prescribed antidepressants. CONCLUSIONS: Our results showed the use of high doses of antipsychotics, high percentages of antipsychotic polypharmacy and concurrent use of hypnotics/anxiolytics in patients with schizophrenia. Notably, these data were collected before intensive instruction regarding the guidelines; therefore, we need to assess the change in the prescription pattern post guideline instruction.


Assuntos
Antipsicóticos , Transtorno Depressivo Maior , Esquizofrenia , Adulto , Idoso , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Alta do Paciente , Prescrições , Esquizofrenia/tratamento farmacológico
18.
Psychiatry Res ; 303: 114086, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34246008

RESUMO

Herein we evaluate the impact of COVID-19 restrictions on antidepressant effectiveness of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD). We conducted a case series analysis of adults with TRD (n = 267) who received four ketamine infusions at an outpatient clinic in Ontario, Canada, during COVID-19 restrictions (from March 2020 - February 2021; n = 107), compared to patients who received treatment in the previous year (March 2019 - February 2020; n = 160). Both groups experienced significant and comparable improvements in depressive symptoms, suicidal ideation, and anxiety with repeated ketamine infusions. Effectiveness of IV ketamine was not attenuated during the COVID-19 period.


Assuntos
COVID-19 , Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Adulto , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Infusões Intravenosas , Ketamina/uso terapêutico , Ontário , Pandemias , SARS-CoV-2
19.
J Affect Disord ; 293: 268-275, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34217965

RESUMO

BACKGROUND: Major depressive disorder (MDD) is one of the most prevalent mental disorders during adolescence, and early diagnosis and treatment are important. We aimed to characterize the microstructure of the brain in medication-naïve adolescents with first-episode MDD. METHODS: Patients with MDD (N = 31) and healthy controls (N = 27) participated in this study and severity of depressive symptoms, duration of untreated depressive episode, demographic data, and diffuse tensor imaging data were collected. A comparative analysis of patients and healthy controls was performed, and the effect of medication on the brain`s integrity was investigated through comparison before and after 3 months of treatment in the patient group. Tract-based spatial statistics was used for diffusion tensor image analysis. RESULTS: In the patient group, functional anisotropy (FA) values were significantly higher at the genu of the corpus callosum, body of the corpus callosum, and right anterior corona radiata than in healthy controls. After 3 months of treatment, FA values were significantly decreased in the left anterior limb of the internal capsule, left posterior limb of the internal capsule, and left superior longitudinal fasciculus. LIMITATIONS: The sample size is relatively small and 3-month treatment period was relatively short. CONCLUSION: FA values of patients with MDD were increased compared to healthy controls and decreased after treatment. These results suggested that pharmacological treatments in the early stages of MDD might restore the brain`s integrity.


Assuntos
Transtorno Depressivo Maior , Substância Branca , Adolescente , Anisotropia , Encéfalo/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Imagem de Tensor de Difusão , Humanos , Estudos Prospectivos , Substância Branca/diagnóstico por imagem
20.
J Affect Disord ; 293: 355-362, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34233228

RESUMO

BACKGROUND: Estrogen fluctuations throughout the lifespan may contribute to major depressive disorder (MDD) risk in women through effects on brain networks important in stress responding, and mood regulation. Although there is evidence to support ovarian hormone treatment for peri-menopausal depression, postmenopausal use has not been well examined. The objective of this study was to investigate whether estrogen modulation of the neural and emotional cognitive responses to stress differs between postmenopausal women with and without MDD history. METHODS: 60 postmenopausal women completed an fMRI psychosocial stress task, after receiving no drug or 3 months of daily estradiol (E2). fMRI activity and subjective mood response were examined. RESULTS: In women without a history of MDD, E2 was associated with a more negative mood response to stress and less activity in emotional regulation regions. In women with a history of MDD, E2 was associated with a less negative mood response to stress and less activity in emotion perception regions. LIMITATIONS: This study was limited by open-label estradiol administration and inclusion of participants using antidepressants. CONCLUSIONS: These results support a differential effect of estrogen on emotional and neural responses to psychosocial stress in postmenopausal women with MDD history and may reflect a shift in brain activity patterns related to emotion processing following menopause.


Assuntos
Transtorno Depressivo Maior , Angústia Psicológica , Transtorno Depressivo Maior/tratamento farmacológico , Emoções , Estradiol , Estrogênios , Feminino , Humanos , Pós-Menopausa , Estresse Psicológico
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