Weeks Of Escitalopram Treatment Research Articles

Effects of escitalopram therapy on effective connectivity among core brain networks in major depressive disorder

BackgroundPatients with major depressive disorder (MDD) have abnormal functional interaction among large-scale brain networks, indicated by aberrant effective connectivity of the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). However, it remains unclear whether antidepressants can normalize the altered effective connectivity in MDD. MethodsIn this study, we collected resting-state functional magnetic resonance imaging data from 46 unmedicated patients with MDD at baseline and after 12 weeks of escitalopram treatment. We also collected data from 58 healthy controls (HCs) at the same time point with the same interval. Using spectral dynamic causal modeling and parametric empirical Bayes, we examined group differences, time effect and their interaction on the casual interactions among the regions of interest in the three networks. ResultsCompared with HCs, patients with MDD showed increased positive (excitatory) connections within the DMN, decreased positive connections within the SN and DAN, decreased absolute value of negative (inhibitory) connectivity from the SN and DAN to the DMN, and decreased positive connections between the DAN and the SN. Furthermore, we found that six connections related to the DAN showed decreased group differences in effective connectivity between MDD and HCs during follow-up compared to the baseline. ConclusionsOur findings suggest that escitalopram therapy can partly improve the disrupted effective connectivity among high-order brain functional networks in MDD. These findings deepened our understanding of the neural basis of antidepressants' effect on brain function in patients with MDD.

Psychoneuroendocrine profiles of unmedicated men with major depressive disorder and associations to treatment effects and sexual side-effects

Sex hormones are potentially involved in major depressive disorder (MDD) as there are sex differences in risk for depression, symptomatology and treatment efficacy. Such hormonal contributions to MDD have mainly been studied in women and scarcely in men. We, therefore, investigate whether testosterone and estradiol levels in unmedicated men with MDD are associated with depressive symptom profiles, SSRI treatment response, and sexual side-effects. Pretreatment plasma testosterone and estradiol were available from 26 unmedicated men (age 18–49). The patients were treated with 10–20 mg escitalopram for 12 weeks. Depression severity was measured by Hamilton Depression Rating Scale 17 (HAMD17), and treatment response was the change in HAMD6 from baseline. Sexual side-effects were assessed with a standardized clinician-rated scale. Pretreatment testosterone was positively associated with depression severity (p = 0.016), the association was primarily driven by vegetative symptoms: weight loss, gastrointestinal symptoms, and insomnia (p ≤ 0.027). Pretreatment sex hormone levels were not associated with antidepressant treatment outcome. However, pretreatment sex hormones were lower in patients who experienced sexual side-effects after 8–12 weeks of escitalopram treatment; low estradiol was associated with erectile and ejaculatory dysfunction (p = 0.039) and low testosterone and low estradiol were both associated with decreased libido (p ≤ 0.004). In conclusion, we find low testosterone in men with MDD coupled with depression severity, particularly vegetative symptoms. However, pretreatment sex hormone levels were not associated with treatment efficacy but with sexual side-effects. Taken together, our findings highlight sex hormone profiles as potential prognostic biomarkers of SSRI-induced sexual dysfunction. Data fromClinical study (NCT02869035).

Hyperconnecitivity between dorsal attention and frontoparietal networks predicts treatment response in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) presented with repetitive obsessions and/or compulsions were associated with disrupted resting-state functional connectivity (rs-FC). To investigate the pharmacological treatment effect on rs-FC changes in OCD patients we conducted the seed-to-voxel FC analyses using dorsal attention network (DAN), default mode network (DMN), salience network (SN) and frontoparietal network (FPN) and basal ganglia seeds. Twenty-two healthy subjects and twenty-four unmedicated OCD patients underwent resting-state functional magnetic resonance imaging. Patients were rescanned after 12 weeks of escitalopram treatment. We found increased FC both within the DAN and between the DAN and the FPN which was ameliorated after medication and correlated significantly with the clinical improvement in obsession scores. We also observed an anticorrelation between the left caudate and the supplementary motor area in unmedicated OCD patients which also normalized with treatment. Results further showed treatment related normalization of orbitofrontal cortex hyperconnectivity with DMN and hypoconnectivity with DAN whereas aberrant FC between the SN and visual areas appears to be a medication effect. We suggest that DAN to FPN hyperconnectivity which is positively correlated with clinical improvement in obsession scores at pre-treatment stage in present study has a potential for being a neuroimaging marker to predict the treatment response in OCD.

Longer term benefits of exercise and escitalopram in the treatment of anxiety in patients with coronary heart disease: Six month follow-up of the UNWIND randomized clinical trial

Anxiety is a common comorbidity in patients with coronary heart disease (CHD) and is associated with worse prognosis. However, effective treatment for anxiety in CHD patients is uncertain. The UNWIND randomized clinical trial showed that 12-week treatment of escitalopram was better than exercise training or placebo in reducing anxiety in anxious CHD patients. The longer-term benefits of treatment for anxiety are not known. Patients were randomized to 12 weeks of Escitalopram (up to 20 mg), Exercise (3 times/wk), or placebo pill. At the conclusion of treatment, participants were followed for 6-months to determine the persistence of benefit on the primary anxiety endpoint assessed by the Hospital Anxiety and Depression Scale-Anxiety scale (HADS-A) and to assess the effects of treatment on major adverse cardiac events over a follow-up period of up to 6 years. Of the 128 participants initially randomized, 120 (94%) were available for follow-up. Participants randomized to the Escitalopram condition exhibited lower HADS-A scores (3.9 [3.1, 4.7]) compared to those randomized to Exercise (5.5 [4.6, 6.3]) (P = .007) and Placebo (5.3 [4.1, 6.5]) (P = .053). Over a median follow-up of 3.2 years (IQR: 2.3, 4.5), there were 29 adverse events but no significant between-group differences. In the UNWIND trial, 12 weeks of escitalopram treatment was effective in reducing anxiety. These beneficial effects were sustained for 6 months posttreatment. Although moderate or vigorous physical activity has a number of health benefits, exercise was not an effective treatment for anxiety in patients with CHD.

Identification of antisense lncRNAs targetingGSK3β as a regulator in major depressive disorder.

Aim: To identify lncRNAs targeting GSK3β in MDD. Materials & methods: The levels of GSK3β and its three targeting lncRNAs (gsk3β antisense AS1, AS2 and AS3) were detected in 52 patients with major depressive disorder (MDD)before and after 8weeks of escitalopram treatment. The functional study was evaluated using the silence of lncR-gsk3βAS2/3. The correlation between lncRNA-gsk3β and 89 MDD patients was analyzed. Human neuron progenitor cellswere used to investigate the functional role of lncRNA-gsk3β in MDD. Results: All three lncRNAs were downregulated in MDD patients but upregulated after treatment. Inhibition of gsk3βAS2/3 reduced GSK3β expression and its phosphorylation levels in the neuron progenitor cells. Conclusion: Our findings suggestthat lncRNA-gsk3βAS3 regulates GSK3β activity in MDD and has potential as a novel therapeutic target.

Cortical Thickness of the Salience Network and Change in Apathy Following Antidepressant Treatment for Late-Life Depression

ObjectiveApathy is common in late-life depression and is associated with poor response to antidepressant drugs. In depressed older adults, apathy may be characterized by neuroanatomical abnormalities of the salience network. The current study examined whether cortical thickness of select salience network structures predicted change in apathy following a 12-week treatment with escitalopram. MethodsA sample of 46 older adults with major depressive disorder received 12 weeks of escitalopram treatment at a daily target dose of 20 mg. All participants underwent a structural brain MRI scan at baseline, and cortical thickness was estimated in key cortical nodes of the salience network: the caudal anterior cingulate cortex and the insula. We measured baseline and post-treatment symptoms using the Apathy Evaluation Scale and the Hamilton Depression Rating Scale. ResultsA thicker insula at baseline predicted reduction in apathy symptoms following 12 weeks of treatment with escitalopram, even when controlling for age, baseline depression severity and change in depressive symptoms. ConclusionReduced insular thickness predicted residual apathetic symptoms following escitalopram treatment. These results converge with our previous findings of abnormal functional connectivity of the insular cortex in older depressed individuals with apathy. Older depressed adults with apathy may benefit from alternative treatment approaches or augmentative interventions that target abnormalities of the salience network.

An investigation of cortical thickness and antidepressant response in major depressive disorder: A CAN-BIND study report

Major depressive disorder (MDD) is considered a highly heterogeneous clinical and neurobiological mental disorder. We employed a novel layered treatment design to investigate whether cortical thickness features at baseline differentiated treatment responders from non-responders after 8 and 16 weeks of a standardized sequential antidepressant treatment. Secondary analyses examined baseline differences between MDD and controls as a replication analysis and longitudinal changes in thickness after 8 weeks of escitalopram treatment. 181 MDD and 95 healthy comparison (HC) participants were studied. After 8 weeks of escitalopram treatment (10-20mg/d, flexible dosage), responders (>50% decrease in Montgomery-Åsberg Depression Scale score) were continued on escitalopram; non-responders received adjunctive aripiprazole (2-10mg/d, flexible dosage). MDD participants were classified into subgroups according to their response profiles at weeks 8 and 16. Baseline group differences in cortical thickness were analyzed with FreeSurfer between HC and MDD groups as well as between response groups. Two-stage longitudinal processing was used to investigate 8-week escitalopram treatment-related changes in cortical thickness. Compared to HC, the MDD group exhibited thinner cortex in the left rostral middle frontal cortex [MNI(X,Y,Z=-29,9,54.5,-7.7); CWP=0.0002]. No baseline differences in cortical thickness were observed between responders and non-responders based on week-8 or week-16 response profile. No changes in cortical thickness was observed after 8 weeks of escitalopram monotherapy. In a two-step 16-week sequential clinical trial we found that baseline cortical thickness does not appear to be associated to clinical response to pharmacotherapy at 8 or 16 weeks.

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.

Whole-genome expression analysis reveals genes associated with treatment response to escitalopram in major depression

The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1±11.6 years, 68% females) treated with escitalopram 10–20mg/day for 12 weeks, from which 87 patients (55 females) were included in gene expression analyzing. The gene expression profiles were measured on peripheral blood cells at baseline, at week 4 and at the end of treatment (week 12) using BeadChips Illumina. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). The most interesting gene, which showed the predictive effect on treatment outcome by delineating low dose responders and treatment-resistant patients at the beginning of medication, was NLGN2, belonging to a family of neuronal cell surface proteins and involving in synapse formation. In addition, the several gene clusters, related to immune response, signal transduction and neurotrophin pathway, have distinguished responders from non-responders at the week 4 of treatment. After 4 weeks of escitalopram treatment (10mg/day), the YWHAZ gene has showed the highest transcriptional change in responders as compared with non-responders. Finally, at the end of the treatment we noticed that at least three genes (NR2C2, ZNF641, FKBP1A) have been strongly associated with resistance to escitalopram. Thus the results of this study support that exploration of peripheral gene expression is a useful tool in the further identification of novel genetic biomarkers for antidepressant treatment response.

Long-term administration of escitalopram in patients with social anxiety disorder in Japan.

PurposeTo investigate the safety, tolerability, and effectiveness of escitalopram in patients with social anxiety disorder in Japan.MethodsA 52-week, open-label study was conducted in Japanese patients with social anxiety disorder with a total score ≥60 on the Liebowitz Social Anxiety Scale – Japanese Version (LSAS-J) and ≥4 on the Clinical Global Impression – Severity Scale. Escitalopram 10 mg/day was administered for the first week and could be increased to 20 mg/day.ResultsThe study included 158 patients: 81.0% (128/158) completed 52 weeks of escitalopram treatment, 68.4% (108/158) increased their dose to 20 mg/day, and 56.3% (89/158) remained on 20 mg/day. Adverse drug reactions were reported by 57.6% (91/158) of patients. The most common (incidence ≥10%) were somnolence and nausea. The incidence of adverse drug reactions was similar in extensive and poor metabolizers of cytochrome P450 2C19. No adverse drug reactions increased in incidence by >5% after week 12. The incidence of serious adverse events was 1.3% (2/158). No deaths occurred. The LSAS-J total scores improved until week 52. The LSAS-J response rate (≥30% improvement in LSAS-J) was 69.0%, the Clinical Global Impression – Improvement Scale response rate (≤2) was 73.0%, and the LSAS-J remission rate (≤30) was 27.0%.ConclusionIn this first 52-week clinical study of social anxiety disorder, escitalopram 10–20 mg/day was safe, well tolerated, and effective in Japanese patients.

Serotonin-Related Polymorphisms in TPH1 and HTR5A Genes Are Not Associated with Escitalopram Treatment Response in Korean Patients with Major Depression

Background/Aims: The genetic variations in serotonin-related genes may be associated with antidepressant treatment response in major depressive disorder (MDD). The tryptophan hydroxylase-1 (TPH1) gene and serotonin 5A receptor (HTR5A) gene are known to be involved in serotonin biosynthesis and signal transduction, respectively. The purpose of this study was to investigate a possible interaction between the TPH1 gene and the HTR5A gene in the treatment outcome of escitalopram in MDD. Methods: In total, 245 patients diagnosed with MDD were recruited, and their symptoms were evaluated using the 17-item Hamilton Depression Rating scale (HAMD-17). The association between the TPH1 218A/C and HTR5A 12A/T polymorphisms and the clinical outcomes (remission, response and changes in HAMD-17 score) was investigated after 2, 4 and 8 weeks of escitalopram treatment using multiple logistic regression or multiple linear regression analysis. Results: No significant associations of TPH1 or HTR5A gene polymorphisms were observed with either response rate or remission rate at 2, 4 and 8 weeks after escitalopram treatment. In addition, the gene-gene interaction between TPH1 and HTR5A genes was not associated with the treatment outcome. Conclusions: Our results suggest that TPH1 218A/C and HTR5A 12A/T polymorphisms cannot predict treatment response in major depression.

ATP-binding cassette sub-family F member 1 (ABCF1) is identified as a putative therapeutic target of escitalopram in the inflammatory cytokine pathway

The inflammatory cytokine pathway may be a potential therapeutic target for major depressive disorder (MDD). Previous reports suggest that antidepressants have anti-inflammatory properties and can cause a reduction in proinflammatory cytokines. Recent evidence suggests this might be mediated at the level of the transcriptome. The current study investigated the transcription of 86 genes in the inflammatory cytokine pathway both at baseline and after eight weeks of escitalopram treatment in MDD patients who were either clinical responders (n=25) or non-responders (n=21), using a subset of samples in the Genome-Based Therapeutic Drugs for Depression project (GENDEP). Changes in expression between baseline and eight weeks of treatment were assessed using two-tailed t-tests. To establish if any significant expression changes related to clinical response, the magnitude of the relative expression change between baseline and eight weeks of treatment was established and binary logistic regressions were used to compare differences between responders and non-responders. ATP-binding cassette sub-family F member 1 (ABCF1), a translational regulator of the inflammatory cytokine pathway showed a significant increase in expression after escitalopram treatment which was significantly greater in responders compared to non-responders, suggesting that ABCF1 may play a role in mediating antidepressant response.

Effect of Escitalopram on Mental Stress–Induced Myocardial Ischemia

Mental stress can induce myocardial ischemia and also has been implicated in triggering cardiac events. However, pharmacological interventions aimed at reducing mental stress-induced myocardial ischemia (MSIMI) have not been well studied. To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters. The REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) study, a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center. Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg/d, with titration to 20 mg/d in 3 weeks) or placebo over 6 weeks. Occurrence of MSIMI, defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in 2 or more leads, lasting for 3 or more consecutive beats, during 1 or more of 3 mental stressor tasks. Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed end point assessments (n = 56 in each group). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4%-43.0%]) had absence of MSIMI during the 3 mental stressor tasks compared with patients taking placebo (17.5% [95% CI, 10.4%-24.5%]), based on the unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (odds ratio, 2.62 [95% CI, 1.06-6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6%-55.0%]) than in patients receiving placebo (52.5% [95% CI, 43.3%-61.8%]), but this difference was not statistically significant (adjusted odds ratio; 1.24 [95% CI, 0.60-2.58]; P = .56). Among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI. There was no statistically significant difference in exercise-induced ischemia. Replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed. clinicaltrials.gov Identifier: NCT00574847.

Escitalopram for antipsychotic nonresponsive visual hallucinosis: eight patients suffering from Charles Bonnet syndrome

The Charles Bonnet syndrome (CBS) is characterized by distinct visual hallucinations and ocularpathology causing visual impairment in patients with insight and the absence of psychiatric comorbidity. The number of reported cases of CBS is expanding as the population ages and the prevalence of vision disorders increases. Antipsychotic medications are often prescribed. However, their efficacy in CBS has been based on sketchy evidence. The use of serotonin selective reuptake inhibitor (SSRI) for CBS was anecdotally reported. We herein describe effectiveness of escitalopram in a series of patients suffering from CBS who were unresponsive to antipsychotic treatment. Eight consecutive patients suffering from CBS who did not respond to standard antipsychotic treatment were switched to escitalopram. CBS severity prior to escitalopram treatment was quantified using the Clinical Global Impression (CGI) scale and again after eight weeks of treatment. All had undergone brain CT and cognitive assessment. Brain CT imaging was normal except for an incidental finding of a small frontal meningioma in one patient. All had Mini-Mental Status Examination scores of ≥ 27/30. There were four men and four women, with a mean age of 81.7 ± 7.3 years. Previous antipsychotic treatment was mostly with risperidone, 1.0 to 3.0 mg/daily. Mean CGI-severity upon switching to escitalopram treatment was 5.7. This was significantly reduced to 1.8 (p < 0.001) after eight weeks of escitalopram treatment (mean dose: 11.8 mg/daily). There were no side effects, nor any adverse events were reported. This is the first case-series to show that SSRI is an effective and well-tolerated treatment for visual hallucinations associated with vision impairment such as in CBS.

CYP2D6 P34S Polymorphism and Outcomes of Escitalopram Treatment in Koreans with Major Depression

ObjectiveCytochrome P450 (CYP) enzymatic activity, which is influenced by CYP genetic polymorphism, is known to affect the inter-individual variation in the efficacy and tolerability of antidepressants in major depressive disorder (MDD). Escitalopram is metabolized by CYP2D6, and recent studies have reported a correlation between clinical outcomes and CYP2D6 genetic polymorphism. The purpose of this study was to determine the relationship between the CYP2D6 P34S polymorphism (C188T, rs1065852) and the efficacy of escitalopram treatment in Korean patients with MDD.MethodsA total of 94 patients diagnosed with MDD were recruited for the study and their symptoms were evaluated using the 21-item Hamilton Depression Rating scale (HAMD-21). The association between the CYP2D6 P34S polymorphism and the clinical outcomes (remission and response) was investigated after 1, 2, 4, 8, and 12 weeks of escitalopram treatment using multiple logistic regression analysis and χ2 test.ResultsThe proportion of P allele carriers (PP, PS) in remission status was greater than that of S allele homozygotes (SS) after 8 and 12 weeks of escitalopram treatment. Similarly, P allele carriers exhibited a greater treatment response after 8 and 12 weeks of escitalopram treatment than S allele homozygotes.ConclusionOur results suggest that the P allele of the CYP2D6 P34S polymorphism is a favorable factor in escitalopram treatment for MDD, and that the CYP2D6 P34S polymorphism may be a good genetic marker for predicting escitalopram treatment outcomes.

2218 – Brain-derived neurotrophic factor gene polymorphism (val66met) and the response to escitalopram in depression

Introduction The Brain-derived neurotrophic factor (BDNF) gene is a candidate gene for influencing the clinical response to treatment with antidepressants. Objective The aim of the study was to determine the effects of 3 and 6 weeks of escitalopram treatment in depressed patients subdivided according to the treatment response. Methods We included 188 French subjects with depression, 153 completed a 6-week treatment with escitalopram (10–20 mg/d). Clinical evaluation was performed using the Montgomery and Asberg Depression Rating Scale (MADRS) before treatment and after 3 and 6 weeks of treatment. Results At 3 weeks of escitalopram treatment, the Met carriers had increased antidepressant response in comparison to Val/Val homozygotes. No significant clinical difference between genotype groups remained at 6 weeks of escitalopram treatment. Conclusions Our findings further support that the Brain-Derived Neurotrophic Factor gene polymorphism (Val66Met) may play a role in antidepressant treatment response phenotypes in mood depressive episode.

Association between Serotonin Transporter-Linked Polymorphic Region and Escitalopram Antidepressant Treatment Response in Korean Patients with Major Depressive Disorder

Objective: Various studies have shown that short (s)/long (l) polymorphisms of the serotonin transporter-linked polymorphic region (5-HTTLPR) might predict treatment outcome to selective serotonin reuptake inhibitors. The purpose of this study was to evaluate the association between 5-HTTLPR and clinical response to escitalopram treatment in Korean subjects with major depressive disorder. Methods: One hundred and fifteen Korean patients diagnosed with major depressive disorder were evaluated during 8 weeks of escitalopram treatment at a dose of 5–20 mg/day. Patients were genotyped for 5-HTTLPR using polymerase chain reaction. Clinical symptoms were evaluated by the 21-item Hamilton Depression Rating (HAMD-21) scale during the 8 weeks of treatment. Results: Therapeutic response to antidepressant escitalopram was better in s allele carriers (ss, sl) than in l allele homozygotes (ll) at 8 weeks of treatment (OR = 6.24, p = 0.026). The proportion of s allele carriers in responders was higher than that in non-responders (96.6 vs. 85.7%). The percentile decline in HAMD-21 in s allele carriers (59.86 ± 3.23%) was larger than that in HAMD-21 in l allele homozygotes (43.13 ± 11.49%; p = 0.029). However, 5-HTTLPR genotypes were not significantly associated with remission (p > 0.05). Conclusions: Our results show that treatment response to escitalopram at 8 weeks was moderated by 5-HTTLPR, with better response rates for s allele carriers than for l allele homozygotes. Although the role of 5-HTTLPR as a definite predictor of selective serotonin reuptake inhibitor treatment response cannot be confirmed from current results, they do suggest a trend for better response in s allele carriers.

Changes in gray matter volume of remitted first-episode, drug-naïve, panic disorder patients after 6-week antidepressant therapy

ObjectiveThis study aimed to investigate changes in the gray matter volume (GMV) of first-episode, remitted drug-naïve patients under 6 weeks of escitalopram treatment for panic disorder (PD). We also determined any persistent GMV deficits after remission to assess for “state-dependent brain changes” and “trait-like brain changes” for PD. Method3-Tesla magnetic resonance imaging structural scans were performed on 21 PD patients at baseline and in their remitted state at week 6 of the study. To account for the inter-scanner bias, 21 healthy controls were also scanned twice within 6 weeks. All structural images were processed and analyzed to estimate GMV differences between patients and controls. We utilized optimized voxel-based morphometry with global brain volume, age, and gender as covariates. We also estimated the correlation between improvements in clinical rating scale scores and changes in total gray matter volumes to confirm the results of optimized voxel-based morphometry. ResultsRating scales of panic symptoms improved significantly (corrected p < 0.001). Remitted patients showed increased GMV in the left superior frontal gyrus (corrected p < 0.05) after escitalopram therapy. There were significant GMV deficits in the right precentral gyrus (corrected p < 0.05) after remission of PD symptoms. Changes in total GMV after remission were correlated with changes in clinical scores (r = 0.638; Spearman's rho p = 0.002). ConclusionThe left superior frontal gyrus (state-dependent brain changes) and the right precentral gyrus (trait-like brain changes) might be implicated in the underlying pathophysiology of PD.

Different levels of lack of improvement at 4 weeks of escitalopram treatment as predictors of poor 8-week outcome in MDD

BackgroundSeveral post-hoc studies have shown that lack of early improvement reduces the chance of later response or remission. This post-hoc analysis evaluates different cut-off points of non-improvement at 4 weeks of escitalopram treatment to predict 8-week non-response and non-remission. MethodThis study consisted of MDD patients with an absence of improvement (<30% reduction in baseline score of the HAMD-17) at Week 4 of escitalopram treatment (10mg/day) that continued escitalopram treatment (10–20mg/day) for a further 4-week period (n=251). Predictive, sensitivity and specificity values for the several definitions of non-improvement (≤25%, ≤20% and ≤15% reduction in the HAMD-17 baseline total score) at 4 weeks were calculated. ResultsOverall, 70.1% (176/251) of patients did not achieve response at Week 8 and 84.5% (212/251) did not achieve remission. The predictive value for non-response was high (71.4–74.3%) for all cut-off points of non-improvement tested. The respective values for non-remission were placed between 85.0% and 87.2%. LimitationsThis was a post-hoc subgroup analysis. The only drug assessed was escitalopram. ConclusionsOur data indicate that an absence of improvement, <30% reduction in the HAMD-17, after 4 weeks of escitalopram treatment should prompt clinicians to consider a change in treatment strategy. Similar findings were previously reported for other antidepressants.

Regional Brain Metabolism and Treatment Response in Panic Disorder Patients: An [18F]FDG-PET Study

Background: Panic disorder (PD) is a common and often chronic psychiatric condition that can lead to considerable disability in daily life. Using [¹⁸F]fluorodeoxyglucose-PET, we examined brain baseline glucose metabolism in PD patients in comparison with normal controls and the changes in glucose metabolism after 12 weeks of escitalopram treatment. Methods: Fifteen patients with PD were compared to 20 normal controls using [¹⁸F]FDG-PET at baseline and brain metabolism after 12 weeks of escitalopram treatment was compared to pretreatment in the patient group using voxel-based statistical analysis and post hoc region-of-interest analysis. Results: Patients with PD showed decreased metabolism in both the frontal, right temporal, and left posterior cingulate gyruses. After 12 weeks of escitalopram treatment, treatment responders showed metabolic increases in global neocortical areas as well as limbic areas whereas nonresponders did not. Conclusion: Abnormal neocortical function appears to be associated with the pathophysiology of PD and escitalopram exerts its therapeutic action by modulating brain activity at the level of the neocortex and limbic system, notably the amygdala and parahippocampal gyrus.