Increased frequency of first-episode poststroke depression after discontinuation of escitalopram.
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ABSTRACT:
SUBMITTER: Mikami K
PROVIDER: S-EPMC3223021 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
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Increased frequency of first-episode poststroke depression after discontinuation of escitalopram.
Mikami Katsunaka K Jorge Ricardo E RE Moser David J DJ Arndt Stephan S Jang Mijin M Solodkin Ana A Small Steven L SL Fonzetti Pasquale P Hegel Mark T MT Robinson Robert G RG
Stroke 20110825 11
<h4>Background and purpose</h4>The purpose of this study was to compare escitalopram, problem-solving therapy, and placebo to prevent poststroke depression during 6 months after discontinuation of treatment.<h4>Methods</h4>We examined for depression 33 patients assigned to placebo, 34 to escitalopram, and 41 to problem-solving therapy.<h4>Results</h4>After controlling for age, gender, prior mood disorder, and severity of stroke, new-onset major depression and Hamilton Depression scores were sign ...[more]
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Project description:ContextDepression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal.ObjectiveTo determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication.Design, setting, and participantsA multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59).Main outcome measuresThe main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria).ResultsPatients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups.ConclusionsIn this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis.Trial registrationclinicaltrials.gov Identifier: NCT00071643.
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Project description:BackgroundReelin is an extracellular glycoprotein involved in several functions of brain development, synaptogenesis and dendritic proliferation. Numerous studies found perturbation in the reelin system and altered serum reelin levels in neuropsychiatric patients using the western blot procedure. In the international literature, this is the first study that made use of an enzyme-linked immunosorbent assay to analyze serum reelin protein concentration quantitatively.RationaleIn order to study possible alterations in reelin blood levels in schizophrenia, we analyzed this signal in schizophrenic patients with a first episode hallucinatory and paranoid syndrome and control subjects in a pilot study design.ResultsWe found increased blood reelin protein concentration in schizophrenic patients compared to healthy controls.DiscussionOur findings point to a relevant role of reelin metabolism in the pathogenesis of schizophrenia.Reelin could be a biomarker for the course of disease or psychopharmacological treatment.ConclusionWe conclude that the reelin protein blood concentration might be a relevant signal with respect to the pathophysiology of schizophrenia.
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Project description:BackgroundUnderstanding the relative risks of maintenance treatment versus discontinuation of antipsychotics following remission in first episode psychosis (FEP) is an important area of practice.MethodA systematic review and meta-analysis. Prospective experimental studies including a parallel control group were identified to compare maintenance antipsychotic treatment with total discontinuation or medication discontinuation strategies following remission in FEP.ResultsSeven studies were included. Relapse rates were higher in the discontinuation group (53%; 95% CIs: 39%, 68%; N = 290) compared with maintenance treatment group (19%; 95% CIs: 0.05%, 37%; N = 230). In subgroup analyses, risk difference of relapse was lower in studies with a longer follow-up period, a targeted discontinuation strategy, a higher relapse threshold, a larger sample size, and samples with patients excluded for drug or alcohol dependency. Insufficient studies included psychosocial functioning outcomes for a meta-analysis.ConclusionsThere is a higher risk of relapse for those who undergo total or targeted discontinuation strategies compared with maintenance antipsychotics in FEP samples. The effect size is moderate and the risk difference is lower in trials of targeted discontinuation strategies.Declaration of interestA.T. has received honoraria and support from Janssen-Cilag and Otsuka Pharmaceuticals for meetings and has been has been an investigator on unrestricted investigator-initiated trials funded by AstraZeneca and Janssen-Cilag. He has also previously held a Pfizer Neurosciences Research Grant. S.M. has received sponsorship from Otsuka and Lundbeck to attend an academic congress and owns shares in GlaxoSmithKline and AstraZeneca. J.H. has attended meetings supported by Sunovion Pharmaceuticals.
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Project description:BackgroundSchizophrenia has long been suggested to represent a disorder with prominent neural dysconnectivity. Gamma-band oscillations are highly relevant in this context, due both to their proposed involvement in neuronal synchronization and to their association with neurotransmitter systems relevant for schizophrenia. Several task-related studies have confirmed reduced power and synchronization of gamma-band oscillations in schizophrenia, but it has been suggested that these findings might not apply to the resting state. The present study aimed to investigate resting-state gamma-band connectivity in patients with schizophrenia.MethodsSixty-four channel resting-state electroencephalography (eyes closed) was recorded in 22 patients with first-episode schizophrenia and 22 healthy controls matched for age and gender. Orthogonalized power envelope correlation was used as a measure of connectivity across 80 cortical regions at 40 Hz. Mean connectivity at each region was compared across groups using the nonparametric randomization approach. Additionally, the network-based statistic was applied to identify affected networks in patients.ResultsPatients displayed increased mean functional gamma-band connectivity compared to controls in the left rolandic operculum. Network-based analyses indicated increased connectivity in patients within a strongly lateralized network consisting mainly of left inferior frontal/orbitofrontal, lateral and medial temporal, and inferior parietal areas. Within this network, gamma-band connectivity was higher in patients with low positive and disorganization symptom levels.ConclusionsThe present study provides a link between resting-state gamma-band connectivity and the core symptoms of schizophrenia. The observed findings are different than those reported by task-related studies, suggesting that resting-state studies might reveal new aspects in the pathophysiology of schizophrenia.
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Project description:Tissue plasminogen activator (tPA) is a serine protease involved in cleavage of neurotrophic factors. In addition, tPA and neuroserpin can also directly bind to low density lipoprotein receptor-related protein 1 (LRP1), promoting neurogenesis and neurite outgrowth. Given both the cleavage and non-cleavage actions of the fibrinolytic system are crucial in neurological functions, the present study, for the first time, systematically detected the changes of fibrinolytic system factors in rats exposed to chronic unpredictable mild stress (CUMS) or lipopolysaccharide (LPS) and patients with depression. In general, our data demonstrated that both CUMS and LPS reduced tPA but elevated plasminogen activator inhibitor-1 (PAI-1; SERPINE1) mRNA expression. Intriguingly, decreased expression of neuroserpin and LRP1 was also observed in rats exposed to CUMS or LPS. The down-regulated neuroserpin and LRP1 signaling were confirmed by western blotting and immunoflurence data. Likewise, elevated PAI-1 but a significant reduction of neuroserpin and LRP1 mRNA expression were observed in the peripheral blood mononuclear cells (PBMCs) of patients with first-episode depression, and the mRNA levels of PAI-1, neuroserpin and LRP1 were correlated with the Beck Depression inventory (BDI) scores, further strengthening the clinical significance and involvement of the fibrinolytic system in depression. Collectively, the present study demonstrated the alterations of fibrinolytic system in stressed and inflamed brain and in patients with first-episode depression, firstly showing that not only the cleavage actions, but also the non-cleavage actions of the system may play an essential role in the development of depression.
| S-EPMC6692056 | biostudies-literature
Project description:BackgroundMajor Depressive Disorder (MDD) is a heterogenous brain disorder, with potentially multiple psychosocial and biological disease mechanisms. This is also a plausible explanation for why patients do not respond equally well to treatment with first- or second-line antidepressants, i.e., one-third to one-half of patients do not remit in response to first- or second-line treatment. To map MDD heterogeneity and markers of treatment response to enable a precision medicine approach, we will acquire several possible predictive markers across several domains, e.g., psychosocial, biochemical, and neuroimaging.MethodsAll patients are examined before receiving a standardised treatment package for adults aged 18-65 with first-episode depression in six public outpatient clinics in the Capital Region of Denmark. From this population, we will recruit a cohort of 800 patients for whom we will acquire clinical, cognitive, psychometric, and biological data. A subgroup (subcohort I, n = 600) will additionally provide neuroimaging data, i.e., Magnetic Resonance Imaging, and Electroencephalogram, and a subgroup of patients from subcohort I unmedicated at inclusion (subcohort II, n = 60) will also undergo a brain Positron Emission Tomography with the [11C]-UCB-J tracer binding to the presynaptic glycoprotein-SV2A. Subcohort allocation is based on eligibility and willingness to participate. The treatment package typically lasts six months. Depression severity is assessed with the Quick Inventory of Depressive Symptomatology (QIDS) at baseline, and 6, 12 and 18 months after treatment initiation. The primary outcome is remission (QIDS ≤ 5) and clinical improvement (≥ 50% reduction in QIDS) after 6 months. Secondary endpoints include remission at 12 and 18 months and %-change in QIDS, 10-item Symptom Checklist, 5-item WHO Well-Being Index, and modified Disability Scale from baseline through follow-up. We also assess psychotherapy and medication side-effects. We will use machine learning to determine a combination of characteristics that best predict treatment outcomes and statistical models to investigate the association between individual measures and clinical outcomes. We will assess associations between patient characteristics, treatment choices, and clinical outcomes using path analysis, enabling us to estimate the effect of treatment choices and timing on the clinical outcome.DiscussionThe BrainDrugs-Depression study is a real-world deep-phenotyping clinical cohort study of first-episode MDD patients.Trial registrationRegistered at clinicaltrials.gov November 15th, 2022 (NCT05616559).
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Project description:ObjectiveTo report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects.Methods188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10-20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2-10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate-adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD-7 ≥ 10) and number of side effects. Covariate-adjusted logistic regression and chi-square tests explored the association between anxious depression and specific side effects.ResultsFor both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p = .010) or had trouble with (IRR = 1.34, p = .026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p < .05).ConclusionPatients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety.
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Project description:Most schizophrenia patients experience psychotic relapses, which may compromise long-term outcome. However, it is difficult to objectively assess the actual risk of relapse for each patient as the biological changes underlying relapse remain unknown. The present study used magnetic resonance imaging (MRI) to investigate the relationship between brain gyrification pattern and subsequent relapse in patients with first-episode schizophrenia. The subjects consisted of 19 patients with and 33 patients without relapse during a 3-year clinical follow-up after baseline MRI scanning. Using FreeSurfer software, we compared the local gyrification index (LGI) between the relapsed and non-relapsed groups. In the relapsed group, we also explored the relationship among LGI and the number of relapses and time to first relapse after MRI scanning. Relapsed patients exhibited a significantly higher LGI in the bilateral parietal and left occipital areas than non-relapsed patients. In addition, the time to first relapse was negatively correlated with LGI in the right inferior temporal cortex. These findings suggest that increased LGI in the temporo-parieto-occipital regions in first-episode schizophrenia patients may be a potential prognostic biomarker that reflects relapse susceptibility in the early course of the illness.
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Project description:BackgroundRecent functional connectivity (FC) studies have proved the potential value of resting-state functional magnetic resonance imaging (rs-fMRI) in the study of major depressive disorder (MDD); yet, the rs-fMRI-based individualized diagnosis of MDD is still challenging.MethodsWe enrolled 82 treatment-naïve first episode depression (FED) adults and 72 matched normal control (NC). A computer-aided diagnosis framework was utilized to classify the FEDs from the NCs based on the features extracted from not only traditional "low-order" FC networks (LON) based on temporal synchronization of original rs-fMRI signals, but also "high-order" FC networks (HON) that characterize more complex functional interactions via correlation of the dynamic (time-varying) FCs. We contrasted a classifier using HON feature (CHON) and compared its performance with using LON only (CLON). Finally, an integrated classification model with both features was proposed to further enhance FED classification.ResultsThe CHON had significantly improved diagnostic accuracy compared to the CLON (82.47% vs. 67.53%). Joint classification further improved the performance (83.77%). The brain regions with potential diagnostic values mainly encompass the high-order cognitive function-related networks. Importantly, we found previously less-reported potential imaging biomarkers that involve the vermis and the crus II in the cerebellum.LimitationsWe only used one imaging modality and did not examine data from different subtypes of depression.ConclusionsDepression classification could be significantly improved by using HON features that better capture the higher-level brain functional interactions. The findings suggest the importance of higher-level cerebro-cerebellar interactions in the pathophysiology of MDD.
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