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Effect of Chronic Escitalopram versus Placebo on Personality Traits in Healthy First-Degree Relatives of Patients with Depression: A Randomized Trial  [PDF]
Ulla Knorr, Maj Vinberg, Erik Lykke Mortensen, Per Winkel, Christian Gluud, J?rn Wetterslev, Ulrik Gether, Lars Vedel Kessing
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031980
Abstract: Introduction The serotonergic neurotransmitter system is closely linked to depression and personality traits. It is not known if selective serotonin reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of their effect on depression. Healthy individuals with a genetic liability for depression represent a group of particular interest when investigating if intervention with SSRIs affects personality. The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD). Methods The trial used a randomized, blinded, placebo-controlled parallel-group design. We examined the effect of four weeks escitalopram 10 mg daily versus matching placebo on personality in 80 people who had a biological parent or sibling with a history of MD. The outcome measure on personality traits was change in self-reported neuroticism scores on the Revised Neuroticism-Extroversion-Openness-Person?alityInventory (NEO-PI-R) and the Eysenck Personality Inventory (EPQ) from entry until end of four weeks of intervention. Results When compared with placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R agreeableness scores significantly compared with placebo (mean; SD) (2.38; 8.09) versus (?1.32; 7.94), p = 0.046), but not following correction for multiplicity. A trend was shown for increased conscientiousness (p = 0.07). There was no significant effect on subclinical depressive symptoms (p = 0.6). Conclusion In healthy first-degree relatives of patients with MD, there is no effect of escitalopram on neuroticism, but it is possible that escitalopram may increase the personality traits of agreeableness and conscientiousness. Trial Registration Clinicaltrials.gov NCT00386841
Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression
Ulla Knorr, Maj Vinberg, Marianne Klose, Ulla Feldt-Rasmussen, Linda Hilsted, Anders Gade, Eva Haastrup, Olaf Paulson, J?rn Wetterslev, Christian Gluud, Ulrik Gether, Lars Kessing
Trials , 2009, DOI: 10.1186/1745-6215-10-66
Abstract: The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.Local Ethics Committee: H-KF 307413Danish Medicines Agency: 2612-3162.EudraCT: 2006-001750-28.Danish Data Agency: 2006-41-6737.ClinicalTrials.gov: NCT 00386841Robins and Guze described five phases in the development of a valid classification of psychiatric illness: clinical description, laboratory studies, delimitation from other disorders, follow-up studies and family studies [1]. Later, response to treatment was added as a sixth phase [2]. Recently, the endophenotype concept has emerged as a strategic tool in neuropsychiatric research [3].Endophenotypes are quantifiable components in the "genes-to-behaviours" pathways distinct from psychiatric symptoms [3]. In parallel with the classification of psychiatric diseases, endophenotypes are validated by specificity, state independence, heritability,
Investigation Of Early Suicide-Related Symptoms In A Non-Suicidal Depressed Patient Population After Escitalopram Administration: A Pilot Study.
Eugenia L. R. Knops,Gilbert M.D. Lemmens,Cornelis van Heeringen,Kurt Audenaert
The Internet Journal of Mental Health , 2010,
Abstract: Background: The efficacy of selective serotonin reuptake inhibitors (SSRIs) is well established in the treatment of major depression. However, an important delay in the onset of global action relative to placebo is described within the first weeks after their administration. Little is known about the experience over time on specific and suicide-related symptoms. Aims: This study aimed at investigating the experience over time of escitalopram on depression-related symptoms that are also associated with increased risk for suicidal behaviour. Methods: In an 8-week prospective uncontrolled open-label design, escitalopram was administered to 18 patients with a current major depressive episode. Mood, state anxiety, state anger and hopelessness were assessed at baseline and after 2, 4 and 8 weeks of treatment with escitalopram in a flexible dose regimen up to 20 mg. Results: Mood (p < 0.001), state anxiety (p = 0.002), state anger (p = 0.002) and hopelessness (p = 0.002) significantly improved after 8 weeks of treatment with escitalopram. However, symptom improvement varied over time. Mood and anger significantly improved after 2 weeks of treatment, whereas significant reductions of state anxiety and hopelessness were noticed only by the end of the study. Conclusions: This study underlines the early beneficial experience of treatment with escitalopram on mood and different suicide-related symptoms in a non-suicidal depressed patient group.
Rationale, design and methodology of a double-blind, randomized, placebo-controlled study of escitalopram in prevention of Depression in Acute Coronary Syndrome (DECARD)
Baiba Hansen, Jamal Hanash, Alice Rasmussen, J?rgen Hansen, Morten Birket-Smith
Trials , 2009, DOI: 10.1186/1745-6215-10-20
Abstract: Two hundred forty non-depressed patients with acute coronary syndrome are randomized to treatment with either escitalopram or placebo for 1 year. Psychiatric and cardiac assessment of patients is performed to evaluate the possibility of preventing depression. Diagnosis of depression and Hamilton Depression Scale are the primary outcome measures.This is the first study of prevention of depression in patients after acute coronary syndrome with a selective serotonin reuptake inhibitor.http://www.ClinicalTrials.gov. webcite Identifier: NCT00140257The prevalence of depression in patients recovering from acute coronary syndrome (ACS) defined as acute myocardial infarction (AMI) and unstable angina pectoris (UAP) has been reported to be 10–40% [1-5]. Depression after ACS is associated with increased mortality and morbidity [6]. Furthermore, cardiac patients with depression have an increased number of visits to general practitioners and are less likely to return to work [5]. Among patients who survive the first post-AMI year, depression is also associated with increased health care costs linked to both hospital readmissions and out-patient contacts [7]. The negative impact of depression has been observed not only in patients with an established diagnosis of depression, but also in patients who reported symptoms of depression during hospitalization [8].Anxiety often occurs simultaneously with depression, and mixed anxiety-depression is found to be present in 90% of depressed patients after AMI [9]. After percutaneous coronary intervention (PCI) patients, who had symptoms of both anxiety and depression, reported poorer health status compared to patients, who only had anxiety or depression or no symptoms [10]. Furthermore, post-AMI anxiety is an independent predictor for both cardiac events and rehospitalizations [11,12]. A history of depression is associated with more frequent angina and poor quality of life after ACS [13]. Depression is related to severity of cardiac disease
Relief of hot flashes with escitalopram in non-depressed menopausal women in Japan: Results of a retrospective analysis  [PDF]
Chikako Mori, Atsushi Imai
Health (Health) , 2012, DOI: 10.4236/health.2012.410136
Abstract: Purpose: Hormone therapy (estrogen with or without progestin) remains the gold standard treatment for hot flashes in menopausal women, but concerns for the risk of hormone therapy have resulted in its decline and a demand for nonhormonal treatments with demonstrated efficacy for hot flashes. Aim of this study was to examine the efficacy of selective serotonin reuptake inhibitor escitalopram on hot flashes in a healthy sample of non-depressant menopausal women in Japan. Methods: We retrospectively analyzed the medical records of 11 menopausal patients with hot flashes, who received escitalopram (10 mg daily) for 2 weeks between March and August 2012. Hot flashes severities and scores were recorded on a scale of 0 to 10 points, at beginning and end of 2 weeks treatment. Results: At 2 weeks of therapy, 9 of 11 patients reported significant decreases in hot flash frequency and severity, but the remission of the symptom was not observed in 2 patients. Speed of relief from hot flashes was rapid (within one week). Conclusions: Escitalopram 10 mg/day may be a prompt and effective option for treating hot flashes in menopausal women who do not want to use hormone replacement therapy.
Burden, Health and Sense of Coherence among Relatives of Depressed Inpatients  [PDF]
Hege Skundberg-Kletthagen, Birgitta Hedelin, Sigrid Wangensteen, Marie Louise Hall-Lord
Open Journal of Nursing (OJN) , 2015, DOI: 10.4236/ojn.2015.53020
Abstract: In Europe, there are an increasing number of persons suffering from depression, which also affects many relatives. The burden and health when being the relative of an inpatient suffering from severe depression has been less examined. The aim of the study was to describe burden, health and sense of coherence among relatives of inpatients with severe depression. Furthermore, the aim was to investigate relatives’ burden in relation to their health and sense of coherence. A cross-sectional design was performed, with a questionnaire consisting of background questions and three instruments; Burden Assessment Scale, General Health Questionnaire and Sense of Coherence scale. The participants consisted of 68 relatives recruited from a sample of inpatients diagnosed with depression in the psychiatric specialist health services in one hospital trust in Norway. The Regional Committee for Medical and Health Research Ethics, Norway South East, gave approval to the study. The relatives reported burden to a various degree, with some reporting a significantly greater burden, poorer health and a weaker sense of coherence than others. With regard to subjective burden eight out of ten relatives reported “Worry about future”, and almost six out of ten were “Upset by change in patient”. Regarding objective burden, more than half the relatives reported having “Less time for friends” and “Reduced leisure time”. In conclusion the relatives with a high level of burden reported more mental distress, poorer health and weaker sense of coherence than those with lower level of burden. Further research should focus on identification of factors predicting burden and health of relatives of inpatients with severe depression.
Inverse Effects of Oxytocin on Attributing Mental Activity to Others in Depressed and Healthy Subjects: A Double-Blind Placebo Controlled fMRI Study  [PDF]
David Pincus,Samet Kose,Ashley Arana,Kevin Johnson,Paul S. Morgan,Jeffrey Borckardt,Tal Herbsman,Fran Hardaway,Mark S. George,Jaak Panksepp,Ziad Nahas
Frontiers in Psychiatry , 2010, DOI: 10.3389/fpsyt.2010.00134
Abstract: Background: Oxytocin is a stress-attenuating and pro-social neuropeptide. To date, no study has looked at the effects of oxytocin in modulating brain activity in depressed individuals nor attempted to correlate this activity with attribution of mental activity in others. Method: We enrolled 10 unmedicated depressed adults and 10 matched healthy controls in a crossover, double blind placebo controlled fMRI 40 i.u. intra-nasal oxytocin study (20 i.u. per nostril). Each subject performed reading the mind in the eyes task (RMET) before and after inhalation of oxytocin or placebo control for a total of 80 scans. Results: Before oxytocin administration, RMET engaged the medial and lateral prefrontal cortex, amygdala, insula and associative areas. Depressed subjects showed increased anterior ventral activation for the RMET minus gender identification contrast whereas matched controls showed increased dorsal and frontal activity. Compared to placebo, oxytocin in depressed subjects showed increased activity in the superior middle frontal gyrus and insula, while controls exhibited more activity in ventral regions. Oxytocin also led to inverse effects in reaction times on attribution task between groups, with controls getting faster and depressed individuals slower to respond. Conclusion: Depression is associated with increased paralimbic activity during emotional mental attribution of others, appearing to be distinctly modulated by oxytocin when compared to healthy controls. Further studies are needed to explore long-term exposure to pro-social neuropeptides on mood in depressed populations and assess their clinical relevance.
Oxybutynin reduces sweating in depressed patients treated with sertraline: a double-blind, placebo-controlled, clinical study
Ghaleiha A, Jahangard L, Sherafat Z, Ahmadpanah M, Brand S, Holsboer-Trachsler E, Bajoghli H, Haghighi M
Neuropsychiatric Disease and Treatment , 2012, DOI: http://dx.doi.org/10.2147/NDT.S36329
Abstract: utynin reduces sweating in depressed patients treated with sertraline: a double-blind, placebo-controlled, clinical study Original Research (1763) Total Article Views Authors: Ghaleiha A, Jahangard L, Sherafat Z, Ahmadpanah M, Brand S, Holsboer-Trachsler E, Bajoghli H, Haghighi M Published Date September 2012 Volume 2012:8 Pages 407 - 412 DOI: http://dx.doi.org/10.2147/NDT.S36329 Received: 24 July 2012 Accepted: 10 August 2012 Published: 14 September 2012 Ali Ghaleiha,1 Leila Jahangard,1 Zahra Sherafat,1 Mohammad Ahmadpanah,1 Serge Brand,2 Edith Holsboer-Trachsler,2 Hafez Bajoghli,3 Mohammad Haghighi1 1Research Center for Behavioral Disorders and Substances Abuse, Hamadan University of Medical Sciences, Hamadan, Iran; 2Psychiatric Hospital of the University of Basel, Center for Affective, Stress and Sleep Disorders, University of Basel, Basel, Switzerland; 3Psychiatry and Psychology Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran Background: Selective serotonin reuptake inhibitors are primarily used in the pharmacological treatment of patients experiencing a major depressive disorder. However, one of the common unwanted effects is excessive sweating or hyperhidrosis. Oxybutynin is an anticholinergic medication which reduces sweating. The aim of this double-blind study was to examine the effect of administration of oxybutynin on subjective sweating in patients treated with sertraline. Methods: A total of 140 patients experiencing a major depressive disorder (mean age 37.69 ± 10.44 years, 86 females [61.4%]) treated with sertraline (mean dose 83 mg/day) were consecutively enrolled in the study, and all reported excessive sweating as a side effect. Thereafter, the patients were randomly assigned to either an oxybutynin 5 mg/day group or to a placebo group. At the beginning and end of the 2-week trial, the patients completed questionnaires related to sweating and medication-related side effects. Results: Over time, subjective sweating reduced significantly in the treatment group as compared with the control group. Oxybutynin-induced side effects were uncommon. Relative to male patients, female patients reported less subjective sweating. Conclusion: Administration of oxybutynin successfully reduced excessive sweating in patients experiencing a major depressive disorder and treated with sertraline. However, possible gender effects should be taken into account.
Comparative efficacy of escitalopram in the treatment of major depressive disorder
Mazen K Ali,Raymond W Lam
Neuropsychiatric Disease and Treatment , 2011,
Abstract: Mazen K Ali, Raymond W LamDepartment of Psychiatry, University of British Columbia, and Mood Disorders Centre, University of British Columbia Hospital, Vancouver, CanadaBackground: Escitalopram is an allosteric selective serotonin reuptake inhibitor (SSRI) with some indication of superior efficacy in the treatment of major depressive disorder. In this systematic review, we critically evaluate the evidence for comparative efficacy and tolerability of escitalopram, focusing on pooled and meta-analysis studies.Methods: A literature search was conducted for escitalopram studies that quantitatively synthesized data from comparative randomized controlled trials in MDD. Studies were excluded if they did not focus on efficacy, involved primarily subgroups of patients, or synthesized data included in subsequent studies. Outcomes extracted from the included studies were weighted mean difference or standard mean difference, response and remission rates, and withdrawal rate owing to adverse events.Results: The search initially identified 24 eligible studies, of which 12 (six pooled analysis and six meta-analysis studies) met the criteria for review. The pooled and meta-analysis studies with citalopram showed significant but modest differences in favor of escitalopram, with weighted mean differences ranging from 1.13 to 1.73 points on the Montgomery Asberg Depression Rating Scale, response rate differences of 7.0%–8.3%, and remission rate differences of 5.1%–17.6%. Pooled analysis studies showed efficacy differences compared with duloxetine and with serotonin noradrenaline reuptake inhibitors combined, but meta-analysis studies did not. The effect sizes of the efficacy differences increased in the severely depressed patient subgroups.Conclusion: Based on pooled and meta-analysis studies, escitalopram demonstrates superior efficacy compared with citalopram and with SSRIs combined. Escitalopram shows similar efficacy to serotonin noradrenaline reuptake inhibitors but the number of trials in these comparisons is limited. Efficacy differences are modest but clinically relevant, especially in more severely depressed patients.Keywords: escitalopram, depressive disorders, meta-analysis, pooled analysis, efficacy, antidepressants
Effect of escitalopram on the processing of emotional faces
Alves-Neto, W.C.;Guapo, V.G.;Graeff, F.G.;Deakin, J.F.W.;Del-Ben, C.M.;
Brazilian Journal of Medical and Biological Research , 2010, DOI: 10.1590/S0100-879X2010005000007
Abstract: serotonin has been implicated in the neurobiology of depressive and anxiety disorders, but little is known about its role in the modulation of basic emotional processing. the aim of this study was to determine the effect of the selective serotonin reuptake inhibitor, escitalopram, on the perception of facial emotional expressions. twelve healthy male volunteers completed two experimental sessions each, in a randomized, balanced order, double-blind design. a single oral dose of escitalopram (10 mg) or placebo was administered 3 h before the task. participants were presented to a task composed of six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) that were morphed between neutral and each standard emotion in 10% steps. escitalopram facilitated the recognition of sadness and inhibited the recognition of happiness in male, but not female faces. no drug effect on subjective measures was detected. these results confirm that serotonin modulates the recognition of emotional faces, and suggest that the gender of the face can have a role in this modulation. further studies including female volunteers are needed.
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