Escitalopram Treatment Research Articles

Escitalopram ameliorates differences in neural activity between healthy comparison and major depressive disorder groups on an fMRI Emotional conflict task: A CAN-BIND-1 study

BackgroundIdentifying objective biomarkers can assist in predicting remission/non-remission to treatment, improving remission rates, and reducing illness burden in major depressive disorder (MDD). MethodsSixteen MDD 8-week remitters (MDD-8), twelve 16-week remitters (MDD-16), 14 non-remitters (MDD-NR) and 30 healthy comparison participants (HC) completed a functional magnetic resonance imaging emotional conflict task at baseline, prior to treatment with escitalopram, and 8 weeks after treatment initiation. Patients were followed 16 weeks to assess remitter status. ResultsAll groups demonstrated emotional Stroop in reaction time (RT) at baseline and Week 8. There were no baseline differences between HC and MDD-8, MDD-16, or MDD-NR in RT or accuracy. By Week 8, MDD-8 demonstrated poorer accuracy compared to HC. Compared to HC, the baseline blood-oxygen level dependent (BOLD) signal was decreased in MDD-8 in brain-stem and thalamus; in MDD-16 in lateral occipital cortex, middle temporal gyrus, and cuneal cortex; in MDD-NR in lingual and occipital fusiform gyri, thalamus, putamen, caudate, cingulate gyrus, insula, cuneal cortex, and middle temporal gyrus. By Week 8, there were no BOLD activity differences between MDD groups and HC. LimitationsThe Emotional Conflict Task lacks a neutral (non-emotional) condition, restricting interpretation of how mood may influence perception of non-emotionally valenced stimuli. ConclusionsThe Emotional Conflict Task is not an objective biomarker for remission trajectory in patients with MDD receiving escitalopram treatment. Escitalopram may have influenced emotion recognition in MDD groups in terms of augmented accuracy and BOLD signal in response to an Emotional Conflict Task, following 8 weeks of escitalopram treatment.

Preventive Effects of Escitalopram Against Anxiety-Like Depressive Behaviors in Monosodium Glutamate-Teated Rats Subjected to Partial Hepatectomy.

The reasons for the relationship between depression and chronic liver disease (CLD) are complex and multifactorial. Further research is needed to decipher the etiology and establish an optimal management approach for depression in patients, including the potential role of non-pharmacological treatments. monosodium glutamate (MSG)-treated rats are more likely to develop anxiogenic- and depressive-like behaviors, which could be related to the dysfunction of serotonergic system. In this study, partial hepatectomy (PH) was performed in MSG-treated rats and the histopathological changes were observed in orbitofrontal cortex (OFC) and liver. The effect of escitalopram, a widely used antidepressant, on neural and liver injury in this model was also examined. The MSG + PH-treated rats displayed decreased distances traveled in total, in center arena, and in the left side of arena in inner open field test (OFT), as compared to saline, saline + PH, and MSG-treated animals. The present study established that PH aggravated anxiety-like depressive behaviors in MSG-treated rats, concordant with damaged Nissl bodies (and neurites), decreased IBA-1 and Sox-2 expression in OFC and neurotransmitter disorder. Escitalopram treatment could alleviate these pathological changes as well as reduce hepatic steatosis and lipid metabolism.

Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants

Major depressive disorder (MDD) is primarily treated with antidepressants, yet many patients fail to respond adequately, and identifying antidepressant response biomarkers is thus of clinical significance. Some hypothesis-driven investigations of epigenetic markers for treatment response have been previously made, but genome-wide approaches remain unexplored. Healthy participants (n = 112) and MDD patients (n = 211) between 18–60 years old were recruited for an 8-week trial of escitalopram treatment. Responders and non-responders were identified using differential Montgomery-Åsberg Depression Rating Scale scores before and after treatment. Genome-wide DNA methylation and gene expression analyses were assessed using the Infinium MethylationEPIC Beadchip and HumanHT-12 v4 Expression Beadchip, respectively, on pre-treatment peripheral blood DNA and RNA samples. Differentially methylated positions (DMPs) located in regions of differentially expressed genes between responders (n = 82) and non-responders (n = 95) were identified, and technically validated using a targeted sequencing approach. Three DMPs located in the genes CHN2 (cg23687322, p = 0.00043 and cg06926818, p = 0.0014) and JAK2 (cg08339825, p = 0.00021) were the most significantly associated with mRNA expression changes and subsequently validated. Replication was then conducted with non-responders (n = 76) and responders (n = 71) in an external cohort that underwent a similar antidepressant trial. One CHN2 site (cg06926818; p = 0.03) was successfully replicated. Our findings indicate that differential methylation at CpG sites upstream of the CHN2 and JAK2 TSS regions are possible peripheral predictors of antidepressant treatment response. Future studies can provide further insight on robustness of our candidate biomarkers, and greater characterization of functional components.

Personality as a Predictor of Treatment Response to Escitalopram in Adults With Body Dysmorphic Disorder.

Serotonin reuptake inhibitors (SRIs) are the first-line pharmacotherapy for body dysmorphic disorder (BDD), a common and severe disorder. However, predictors and correlates of treatment response are not well understood. A closer examination of baseline personality dimensions and disorders and of changes in personality during SRI treatment is needed to advance knowledge of this clinically important issue. We conducted a secondary analysis of data from a pharmacotherapy relapse prevention trial of the SRI escitalopram in adults with BDD to examine personality dimensions and traits, as well as whether these variables predict and correlate with treatment response. A total of 65 participants with BDD completed the Revised NEO Personality Inventory (NEO PI-R) before starting open-label treatment with escitalopram and 42 participants completed the NEO PI-R after treatment. At baseline, participants with BDD displayed higher levels of neuroticism and lower levels of extraversion than a normed reference group. Higher baseline neuroticism was a significant predictor of nonresponse to escitalopram treatment, even when baseline depression severity was controlled for. Changes in neuroticism were not associated with treatment response. Our findings underscore the relationship between BDD and neuroticism, and they suggest a link between neuroticism and SRI treatment response.

Normalization of EEG in depression after antidepressant treatment with sertraline? A preliminary report

BackgroundMDD patients with abnormal EEG patterns seem more likely to be non-responsive to the antidepressants escitalopram and venlafaxine, but not sertraline, than patients without EEG abnormalities. This finding suggests that patients with both MDD and abnormal EEGs may differentially respond to antidepressant treatment. In the current study, we investigated whether depressed patients with an abnormal EEG show a normalization of the EEG related to antidepressant treatment and response and whether such effect is drug specific, and whether having had early life stress (ELS) increases the chance of abnormal activity. MethodsBaseline and week 8 EEGs and depression symptoms were extracted from a large multicenter study (iSPOT-D, n = 1008) where depressed patients were randomized to escitalopram, sertraline, or venlafaxine-XR treatment. We calculated Odds Ratios of EEG normalization and depression response in patients with an abnormal EEG at baseline, comparing sertraline versus other antidepressants. ResultsFifty seven patients with abnormal EEGs were included. EEGs did not normalize significantly more with sertraline compared to other antidepressants (OR = 1.9, p = .280). However, patients with a normalized EEG taking sertraline were 5.2 times more likely to respond than subjects taking other antidepressants (p = .019). ELS was not significantly related to abnormal activity. LimitationsNeurophysiological recordings were limited in time (two times 2-minute EEGs) and statistical power (n = 57 abnormal EEGs). ConclusionsResponse rates in patients with normalized EEG taking sertraline were significantly larger than in subjects treated with escitalopram/venlafaxine. This adds to personalized medicine and suggests a possible drug repurposing for sertraline.

Collaborative Care to Relieve Psychological Distress in Patients with Medically Inoperable Lung Cancer: Design and Rationale for a Clinical Trial.

Psychological distress is common in lung cancer patients with a poor prognosis. The present study aims to investigate the efficacy of collaborative care for patients with newly diagnosed inoperable lung cancer in South Korea. The study is a three-arm parallel-groups nonrandomized clinical trial with an active arm that includes distressed patients who receive collaborative care, one comparison arm that includes distressed patients who receive enhanced usual care, and another comparison arm that includes non-distressed patients. In total, 267 consecutive patients newly diagnosed with medically inoperative lung cancer will be recruited. The primary outcomes are the changes in Hospital Anxiety and Depression Scale-depression and the Distress Thermometer at 12 and 32 weeks after enrollment. Sub-analyses of patients in the active arm of the study will include a comparison of the efficacy of a combination of oral antidepressant (escitalopram) treatment and collaborative care versus that of collaborative care alone.

Trajectories of Suicidal Ideation During 12 Weeks of Escitalopram or Nortriptyline Antidepressant Treatment Among 811 Patients With Major Depressive Disorder.

Suicidal ideation is a frequent and difficult-to-treat clinical challenge among patients with major depressive disorder (MDD). However, little is known regarding the differential development during antidepressant treatment and whether some patients may suffer from persistent suicidal ideation. Among 811 patients with Schedules for Clinical Assessment in Neuropsychiatry (SCAN)-verified MDD from 2004-2007 assessed weekly for 12 weeks of escitalopram or nortriptyline antidepressant treatment, we applied item response theory to integrate a suicidality score based on 3 rating scales. We performed latent growth mixture modeling analysis to empirically identify trajectories. Multinomial logistic regression analyses estimated associations with potential predictors. We identified 5 distinct classes of suicidal ideation. The Persistent-low class (53.7%) showed no suicidal ideation whereas the Persistent-high class (9.8%) had high suicidal ideation throughout 12 weeks. Two classes showed a fluctuating course: the Fluctuating class (5.2%) ended at a low level of suicidal ideation, whereas the Slow-response-relapse class (4.8%) initially responded slowly but then experienced a large increase to a high level of suicidal ideation after 12 weeks. The Fast-response class (26.5%) had a high baseline severity similar to the Persistent-high class but responded quickly within a few weeks and remained at a low level. Previous suicide attempts and higher mood symptom severity were associated with worse suicidal ideation trajectories, whereas living with a partner showed a trend toward better response. Approximately 1 of 5 patients with MDD showed high or fluctuating suicidal ideation despite antidepressant treatment. Studies should investigate whether suicidal ideation may persist for longer periods and more targeted treatment possibilities. ISRCTN​​ identifier: ISRCTN03693000​​​​.

Catechin ameliorates depressive symptoms in Sprague Dawley rats subjected to chronic unpredictable mild stress by decreasing oxidative stress.

Catechin is an active ingredient of green tea. It is reported to inhibit corticosteroid-induced anxiety and depression-like symptoms. Considering the complex nature of depression, effects of catechin need to be studied in a clinically relevant depression model. The present study was designed to explore the antidepressant effect of catechin in Sprague Dawley rats subjected to chronic unpredictable mild stress (CUMS). Animals were subjected to CUMS and treated with (+)-catechin (50 mg/kg) or escitalopram (10 mg/kg) orally; a CUMS control and a vehicle control that was not exposed to CUMS were also established. Various stressors were applied daily in an unpredictable manner for 8 weeks achieve CUMS. Sucrose preference test were performed after 4 and 8 weeks and forced swim tests (FSTs) were conducted at weeks 4, 6 and 8. At the end of week 8, animals were sacrificed and the brain homogenate was studied for antioxidant parameters. Compared with the vehicle control, animals of the CUMS control group showed a significant decrease in sucrose intake. Catechin and escitalopram treatment significantly improved the sucrose intake compared with the CUMS control. A similar trend was observed in the FSTs, where catechin and escitalopram treatment significantly reduced the immobility time, and antioxidant parameters, including catalase, glutathione and superoxide dismutase levels were recovered in treated animals compared with the CUMS control. Thus, it was concluded that catechin reverses CUMS-induced depression in rats by ameliorating oxidative stress, which may help to develop a novel treatment for major depressive disorder.

Associations between cognitions and functional decline in patients with major depressive disorder

Associations between cognitions and functional decline in patients with major depressive disorder

Antidepressant-resistant depression is characterized by reduced short- and long-interval cortical inhibition.

Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram. Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = - 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD. TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.

Brain neurochemistry in unmedicated obsessive-compulsive disorder patients and effects of 12-week escitalopram treatment: 1 H-magnetic resonance spectroscopy study.

The purpose of this study was to examine treatment-related neurochemical changes in 28 unmedicated obsessive-compulsive disorder (OCD) patients using 1 H-magnetic resonance spectroscopy (1 H-MRS). We included subjects diagnosed with OCD (n = 28), each with a total duration of illness of less than 5 years, as a study group and age- and sex-matched healthy controls (n = 26). The inclusion criteria for the OCD group were right-handed individuals aged 18 years or older who had not been on any specific treatment for OCD for the last at least 8 weeks and who had no other psychiatric comorbidity. A pre-post and case-control design was employed in which OCD patients underwent 1 H-MRS at baseline and 12 weeks after treatment with escitalopram (n = 21). Clinical assessment was carried out using a semi-structured pro forma Yale-Brown Obsessive Compulsive Scale and the World Health Organization Disability Assessment Scale 2.0 before and after treatment. Volume-localized 1 H-MRS was carried out with a 3-Tesla Philips MR scanner. Our data suggested higher levels of myoinositol (mI), total choline (tCho), and glutamate+glutamine (Glx) in the medial thalamus at pre-assessment in OCD subjects as compared to healthy controls and a significant reduction in tCho and Glx after treatment in OCD subjects. The mI levels in the caudate nucleus and Glx levels in the anterior cingulate cortex were significantly correlated with disease severity on the Yale-Brown Obsessive Compulsive Scale. Our study supports the hypothesis of a hyper-glutaminergic state (as suggested by increased Glx levels) and neurodegeneration (as suggested by increased tCho and mI in the thalamus) in cortico-striato-thalamocortical circuitry in OCD patients as suggested by previous studies using MRS as well as other functional imaging studies.

Cognitive-functional relationships in major depressive disorder: Crucial data from a Ukrainian open-label study of vortioxetine versus escitalopram

BackgroundMajor depressive disorder (MDD) is one of the most prevalent mental illnesses associated with impairments in different spheres of functioning. Cognitive deficits are currently investigated as a possible factor of functional decline. We aimed: 1) to assess the influence of cognitive domains among other MDD symptoms on functional impairment; 2) to compare effects of eight weeks` vortioxetine versus escitalopram treatments on cognitions and consequent influence on various domains of functioning. MethodsAt baseline, 119 MDD (according to DSM-5, MADRS ≥ 7) patients and 71 healthy controls completed neurocognitive tests (RAVLT, TMT-B, DSST) and Sheehan Disability Scale. After 8 weeks of vortioxetine/escitalopram treatment, 56 patients had repeated clinical and neuropsychological evaluations. Linear regression analyses were performed to find significant predictors of impairment (at baseline) and improvement (after treatment) of functioning. Differences between groups after treatment were analyzed using mixed models for repeated measurements. ResultsCognitive impairments predominantly affected social functioning and were crucial for working productivity and total functioning along with anhedonia, hypothymia. Working memory disturbances impaired all aspects of functioning. Executive dysfunction made an additional contribution to workplace performance disturbances. At week 8, vortioxetine compared with escitalopram greater improved all impaired cognitive parameters and aspects of functioning and had higher remission rates. Cognitive improvement was the most significant factor for total functioning recovery and among crucial contributors to workplace performance recovery. LimitationsNo placebo group. ConclusionCognitions play a key role in social, working, overall functioning in Ukrainian MDD patients. Compared to escitalopram, vortioxetine treatment greater improves all cognitive and functioning domains, which leads to higher remission rates.

Effects of Cytochrome P450 2C19 Genetic Polymorphisms on Responses to Escitalopram and Levels of Brain-Derived Neurotrophic Factor in Patients With Panic Disorder.

The purpose of this study was to examine the relationships between ytochrome P450 family 2 subfamily C member 19 (CYP2C19) polymorphisms, brain-derived neurotrophic factor (BDNF) plasma levels, and treatment responses to escitalopram in Chinese patients with panic disorder (PD). Ninety patients with PD were administered the Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Scale (HAMA-14) from baseline to 8 weeks. Escitalopram treatment (10 mg/d) was administered for 8 consecutive weeks. Three CYP2C19 metabolizers, including extensive metabolizers, intermediate metabolizers, and poor metabolizers (PMs), and 5 CYP2C19 genotypes were detected by polymerase chain reaction-genotyping microarray analysis. Baseline plasma BDNF levels were tested using human BDNF enzyme-linked immunosorbent assay kits. Our findings showed no significant differences in demographic data, baseline PDSS-CV scores, or HAMA-14 scores between the 3 CYP2C19 metabolizer groups (P's > 0.05). Repeated-measures analysis showed a significant reduction in PDSS-CV (F = 221.49, df = 3, P < 0.001) and HAMA-14 (F = 260.47, df = 3, P < 0.001) scores over 8 weeks in PD patients. In addition, patients with PMs had a greater reduction in HAMA-14 scores (F = 2.14, P = 0.049) than did those with extensive metabolizers and intermediate metabolizers. Moreover, our findings showed that patients with *2/*2 genotypes had a greater reduction in PDSS-CV scores than did those with other genotypes (F = 2.14, df = 12, P = 0.015). Our study provides preliminary evidence of the effects of CYP2C19 PMs on treatment responses to escitalopram in Chinese PD patients, but no significant correlation between treatment responses and BDNF levels was found.

Prefrontal networks dynamically related to recovery from major depressive disorder: a longitudinal pharmacological fMRI study

Due to lacking predictors of depression recovery, successful treatment of major depressive disorder (MDD) is frequently only achieved after therapeutic optimization leading to a prolonged suffering of patients. This study aimed to determine neural prognostic predictors identifying non-remitters prior or early after treatment initiation. Moreover, it intended to detect time-sensitive neural mediators indicating depression recovery. This longitudinal, interventional, single-arm, open-label, phase IV, pharmacological functional magnetic resonance imaging (fMRI) study comprised four scans at important stages prior (day 0) and after escitalopram treatment initiation (day 1, 28, and 56). Totally, 22 treatment-free MDD patients (age mean ± SD: 31.5 ± 7.7; females: 50%) suffering from a concurrent major depressive episode without any comorbid DSM-IV axis I diagnosis completed the study protocol. Primary outcome were neural prognostic predictors of depression recovery. Enhanced de-activation of anterior medial prefrontal cortex (amPFC, single neural mediator) indicated depression recovery correlating with MADRS score and working memory improvements. Strong dorsolateral PFC (dlPFC) activation and weak dlPFC-amPFC, dlPFC-posterior cingulate cortex (PCC), dlPFC-parietal lobe (PL) coupling (three prognostic predictors) hinted at depression recovery at day 0 and 1. Preresponse prediction of continuous (dlPFC-PL: R2day1 = 55.9%, 95% CI: 22.6–79%, P < 0.005) and dichotomous (specificity/sensitivity: SP/SNday1 = 0.91/0.82) recovery definitions remained significant after leave-one-out cross-validation. Identified prefrontal neural predictors might propel the future development of fMRI markers for clinical decision making, which could lead to increased response rates and adherence during acute phase treatment periods. Moreover, this study underscores the importance of the amPFC in depression recovery.

Scopolamine augmentation of a newly initiated escitalopram treatment for major depressive disorder: study protocol for a randomized controlled trial

BackgroundMajor depressive disorder (MDD) is a prevalent and disabling disorder that can lead to heavy individual, familial, and societal burdens. Although pharmaceutical interventions still play an essential role in therapeutic measures, limitations, including effects that are delayed for weeks, are noteworthy. Antidepressants with rapid efficacy and acceptable tolerance have been investigated for many years; rapid antidepressant effects and promising clinical applications have been obtained with intravenous and oral scopolamine. This study aims to evaluate the efficacy of repeated intramuscular scopolamine as an add-on treatment to escitalopram.MethodsThis is a single-center, saline-controlled, double-blind, three-armed, randomized trial. Sixty-six participants diagnosed with MDD will be recruited at Beijing Anding Hospital and randomly assigned to one of three groups: a high-dose intramuscular scopolamine augmentation group; a low-dose intramuscular scopolamine augmentation group; and a placebo control group. Our primary endpoint is improvement in the 17-Item Hamilton Rating Scale for Depression (HRSD17) score from the baseline (at least a 20% reduction). Prespecified secondary endpoints include response rates and remission rates as well as changes in the total or subscale scores between the baseline and week 4.DiscussionThis study will provide the first insight regarding the rapid antidepressant efficacy and tolerability of an intramuscular scopolamine add-on to the usual treatment in Chinese MDD patients. The first discussion concerns whether augmentation can accelerate early antidepressant efficacy. A pilot study of intramuscular scopolamine is performed.The limitations of this study include its small sample size and it being a single-center study, suggesting the need for further confirmation with trials enrolling larger populations.Ethics and disseminationThe study protocol and all related materials have been approved by the Institutional Ethics Committee of the Beijing Anding Hospital (No. 2016–106, Beijing, China). The findings will be disseminated through peer-reviewed journals and at national and international conferences.Trial registrationClinicalTrials.gov, NCT03131050. Registered on 18 April 2017.

Pharmacokinetic-Pharmacodynamic interaction associated with venlafaxine-XR remission in patients with major depressive disorder with history of citalopram / escitalopram treatment failure.

The purpose of this study was to identify specific pharmacokinetic (PK) and pharmacodynamics (PD) factors that affect the likelihood of treatment remission with a serotonin norepinephrine reuptake inhibitor (SNRI) in depressed patients whose initial selective serotonin reuptake inhibitor (SSRI) failed. Multiple logistic regression modeling of PK and PD variation hypothesized to contribute to SNRI (i.e. duloxetine or venlafaxine) treatment remission in prior SSRI (i.e. citalopram or escitalopram) failure was conducted on 139 subjects from the Pharmacogenomics Research Network (PGRN) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies. Depressive symptoms were assessed with the Quick Inventory of Depressive Symptomatology Clinician-rated (QIDS-C16). Venlafaxine-XR remission was associated with a significant interaction between CYP2D6 ultra-rapid metabolizer (URM) phenotype and SLC6A4 5-HTTLPR L/L genotype. A similar significant interaction effect was observed between CYP2D6 URM and SLC6A2 G1287A GA genotype. Stratifying by transporter genotypes, venlafaxine-XR remission was associated with CYP2D6 URM in patients with SLC6A4 L/L (p = 0.001) and SLC6A2 G1287A GA genotypes. The primary limitation of this post hoc study was small sample size. Our results suggest that CYP2D6 ultra-rapid metabolizer status contributes to venlafaxine-XR treatment remission in MDD patients; in particular, there is a PK-PD interaction with treatment remission associated with CYP2D6 URM phenotype and SLC6A4 5-HTTLPR L/L or SLC6A2 G1287A G/A genotype, respectively. These preliminary data are encouraging and support larger pharmacogenomics studies differentiating treatment response to mechanistically different antidepressants in addition to further PK-PD interactive analyses.

Diminished responses to monoaminergic antidepressants but not ketamine in a mouse model for neuropsychiatric lupus.

A significant proportion of patients suffering from major depression fail to remit following treatment and develop treatment-resistant depression. Developing novel treatments requires animal models with good predictive validity. MRL/lpr mice, an established model of systemic lupus erythematosus, show depression-like behavior. We evaluated responses to classical antidepressants, and associated immunological and biochemical changes in MRL/lpr mice. MRL/lpr mice showed increased immobility in the forced swim test, decreased wheel running and sucrose preference when compared with the controls, MRL/MpJ mice. In MRL/lpr mice, acute fluoxetine (30 mg/kg, intraperitoneally (i.p.)), imipramine (10 mg/kg, i.p.) or duloxetine (10 mg/kg, i.p.) did not decrease the immobility time in the Forced Swim Test. Interestingly, acute administration of combinations of olanzapine (0.03 mg/kg, subcutaneously)+fluoxetine (30 mg/kg, i.p.) or bupropion (10 mg/kg, i.p.)+fluoxetine (30 mg/kg, i.p.) retained efficacy. A single dose of ketamine but not three weeks of imipramine (10 mg/kg, i.p.) or escitalopram (5 mg/kg, i.p.) treatment in MRL/lpr mice restored sucrose preference. Further, we evaluated inflammatory, immune-mediated and neuronal mechanisms. In MRL/lpr mice, there was an increase in autoantibodies' titers, [3H]PK11195 binding and immune complex deposition. There was a significant infiltration of the brain by macrophages, neutrophils and T-lymphocytes. p11 mRNA expression was decreased in the prefrontal cortex. Further, there was an increase in the 5-HT2aR expression, plasma corticosterone and indoleamine 2,3-dioxygenase activity. In summary, the MRL/lpr mice could be a useful model for Treatment Resistant Depression associated with immune dysfunction with potential to expedite antidepressant drug discovery.

Escitalopram lowers risk of cardiac events in patients with acute coronary syndrome

Use of escitalopram for 24 weeks in patients with depression following acute coronary syndrome (ACS) resulted in a reduced long‐term risk of major adverse cardiac events, a placebo‐controlled study has found. Although the study found no association between escitalopram treatment and mortality outcomes, reduced mortality was associated instead with depressed patients' remission status. Study results were published in the July 24/31 issue of JAMA.

Safety and effectiveness of escitalopram in an 8-week open study in Chinese patients with depression and anxiety.

BackgroundAnxiety symptoms usually worsen depression and functional impairment. The present study was aimed to evaluate the impact of escitalopram on social function and quality of life in major depressive disorder (MDD) patients with anxiety symptoms.Patients and methodsAdult MDD patients with functional impairment (Sheehan Disability Scale [SDS] score ≥9) and anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] score ≥14) received escitalopram (10–20 mg/day) for 8 weeks. Symptom status was assessed by SDS, Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A, and Quick Inventory of Depressive Symptomatology-Self Report scales. Safety was evaluated by treatment-emergent adverse events (TEAEs).ResultsOverall, 208 (79.7%) of 261 enrolled patients completed the 8-week treatment. Mean (SD) SDS and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form total scores were 17.4 (5.87) and 39.3 (14.43) at baseline, which improved to 7.6 (6.71) and 61.6 (15.80), respectively, at week 8. Totally, 59.2% of patients achieved functional remission (SDS≤6) and 61.7% of patients achieved depression remission (MADRS≤10) at week 8; 48.1% of patients achieved both functional and depression remission (SDS≤6 and MADRS≤10). The change in SDS total score was positively correlated with the change in MADRS and HAM-A total scores at each visit. Patient’s baseline SDS score was related with depression score (regression coefficient=0.40582, p=0.0005); remission of SDS was statistically related to a reduction of week 2 and week 6 HAM-A score (p<0.0001) and reduction of MADRS score (p<0.0001). Overall, 25.7% of patients reported ≥1 TEAEs. Most frequently reported TEAEs were nausea (5.8%), diarrhea (2.3%), and dizziness (2.7%). Most TEAEs were mild to moderate in severity. Four patients reported serious TEAEs, two patients reported suicide attempts, and one patient completed suicide.ConclusionEscitalopram (10–20 mg/day) treatment was efficacious in reducing depression, improving social function, and quality of life in MDD patients with anxiety symptoms. No new safety signals were identified.

Update on Randomized Placebo-Controlled Trials in the Past Decade for Treatment of Major Depressive Disorder in Child and Adolescent Patients: A Systematic Review.

Objectives: Antidepressant treatment for major depressive disorder (MDD) has been a topic of continued interest with a number of placebo randomized-controlled trials (RCTs) being published in the past decade. We review the updated literature since the 2007 Bridge meta-analysis, and reassess safety data looking at signals of treatment-emergent suicidality with the Columbia Suicide Severity Rating Scale (CSSR-S). Methods: PubMed literature review was performed searching for RCTs published since the 2007 article and supplemented with manual search. Results: Findings from seven trials (five industry sponsored, one NIMH funded, and one other) were included in this systematic review, which showed high medication and placebo response rates, with only fluoxetine and escitalopram treatment reaching statistical significance. Fluoxetine was also shown to prevent relapse of MDD with continued treatment with an odds ratio of 3.2 for prevention of relapse compared with placebo. There were no increases in treatment-emergent suicidality associated with antidepressant medication in any trial measuring suicidality systematically using the CSSR-S. Conclusions: Depressed pediatric patients respond similarly in these trials to antidepressant intervention and placebo, with recent studies showing that newer agents did not clearly demonstrate benefit above placebo. The evidence continues to support fluoxetine and escitalopram as first-line treatment and demonstrated effect to prevent relapse. Use of newer rating scales reveals similar rates of treatment-emergent suicidality in patients on antidepressants as placebo, in contrast to increased suicide signal suggested by past research using adverse events data. Antidepressant treatment is generally safe and well tolerated in this age group.