Escitalopram Treatment Research Articles

Generic escitalopram initiation and substitution among Medicare beneficiaries: A new user cohort study.

ObjectivesTo examine patterns of generic escitalopram initiation and substitution among Medicare beneficiaries.MethodsThis retrospective new user cohort used a 5% random sample of 2013–2015 Medicare administrative claims data. Fee-for-service Medicare beneficiaries continuously enrolled in Parts A, B, and D during a 6-month washout period prior to their initial generic or brand oral escitalopram prescriptions were included (n = 12,351). The primary outcomes were generic escitalopram treatment initiation, and among brand escitalopram initiators, generic substitution within 12 months. Patient demographics, health service utilization, and prescription level factors were measured and assessed.ResultsAmong all escitalopram initiators, about 88.2% Medicare beneficiaries initiated generic escitalopram. Beneficiaries who were younger age, male, residing in non-Northeast regions or urban area, in the Part D plan deductible benefit phase, and filling prescriptions at community/retail pharmacies were more likely to initiate generic treatment. Among brand escitalopram initiators (n = 1,464), about 20.7% switched to generic escitalopram, 31.2% switched to another alternative antidepressant, 25.1% discontinued treatment, and 8.7% were lost to follow up or passed away within 12 months after brand initiation. Factors associated with generic escitalopram substitution included region (Midwest vs. Northeast, adjusted hazard ratio (HR) = 1.46, 95% CI = 1.04–2.05), pre-index hospitalization (HR = 1.31; 95% CI = 1.16–1.48) and lower escitalopram average daily dosage (HR = 0.97; 95% CI = 0.95–0.99).ConclusionsIn 2013–2015, almost 90% Medicare beneficiaries initiated generic escitalopram treatment. Among brand escitalopram initiators, about 1 in 5 patients switched to generic escitalopram within 1 year, as compared to 1 in 4 or 1 in 3 who discontinued current or switched to alternative treatment, respectively. Medicare beneficiary’s geographic region was independently associated with generic escitalopram initiation and substitution. Findings from this study not only provide up-to-date evidence in generic escitalopram use patterns among Medicare population, but also can guide educational and practice interventions to further increase generic escitalopram use.

Potential depression and antidepressant-response biomarkers in human lymphoblast cell lines from treatment-responsive and treatment-resistant subjects: roles of SSRIs and omega-3 polyunsaturated fatty acids.

While several therapeutic strategies exist for depression, most antidepressant drugs require several weeks before reaching full biochemical efficacy and remission is not entirely achieved in many patients. Therefore, biomarkers for depression and drug-response would help tailor treatment strategies. This study made use of banked human lymphoblast cell lines (LCLs) from normal and depressed subjects; the latter divided into remitters and non-remitters. Due to the fact that previous studies have shown effects on growth factors, cytokines and elements of the cAMP generating system as potential biomarkers for depression and antidepressant action, these were examined in LCLs. Initial gene and protein expression profiles for signaling cascades related to neuroendocrine and inflammatory functions differ among the three groups. Growth factor genes, including VEGFA and BDNF were significantly down-regulated in cells from depressed subjects. In addition, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to act as both antidepressants and anti-inflammatories, but the mechanisms for these effects are not established. Here we showed that n-3 PUFAs and escitalopram (selective serotonin reuptake inhibitors, SSRIs) treatment increased adenylyl cyclase (AC) and BDNF gene expression in LCLs. These data are consistent with clinical observations showing that n-3 PUFA and SSRI have antidepressant affects, which may be additive. Contrary to observations made in neuronal and glial cells, n-3 PUFA treatment attenuated cAMP accumulation in LCLs. However, while lymphoblasts show paradoxical responses to neurons and glia, patient-derived lymphoblasts appear to carry potential depression biomarkers making them an important tool for studying precision medicine in depressive patients. Furthermore, these data validate usefulness of n-3 PUFAs in treatment for depression.

Association between functional polymorphisms in serotonin transporter gene (SLC6A4) and escitalopram treatment response in depressive patients in a South Indian population.

Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder. A total of 148 depressive patients receiving escitalopram 10-20mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student's t test or one-way ANOVA. Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value < 0.001) association between LL genotype, LALA haplotypes, and 2 LA functional group with better treatment response to escitalopram. The decline in HDRS17 and MADRS score from baseline was significantly higher (p value < 0.001) in LL genotypes and homozygous LA carriers compared with other groups. Results suggest that 5HTTLPR and rs-25531 polymorphisms can influence escitalopram treatment response in depressive patients in a South Indian population, LL genotypes and LALA haplotypes being the predictors of better treatment response.

Identification of early candidate urine biomarkers for measure Escitalopram treatment response from major depressive disorder

Major depressive disorder (MDD) is a common mental disorder that can cause substantial impairments in quality of life. Clinical treatment is usually built on trial and error method, which lasts about 12 weeks to evaluate whether the treatment is efficient or not, leading some inefficient treatment measures. We therefore identify early candidate urine biomarkers to predict efficient treatment response in MDD patients. In this study, urine samples were collected from 10 respondent and 10 non‐respondent to escitalopram MDD patients with 0‐, 2‐, and 12‐week treatment. Differential urinary proteins were then analyzed by liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS). On week 2, there were 14 differential proteins identified in response group when compared with week 0 and these proteins can’t be enriched by random allocation analysis, 10 among which have been associated with the mechanisms of MDD. While in non‐response group, there were 35 differential proteins identified on week 2, and 18 among which have been associated with the mechanisms of MDD. In addition, differential urinary proteins on week 2 between respondent and non‐response group can be distinguished clearly by using Orthogonal Partial Least Squares Discrimination Analysis (OPLS‐DA). Our small pilot results indicated that the urine proteome can reflect early changes between respondent and non‐respondent group to escitalopram therapy since on week 2, which will provide potential early candidate urine biomarkers to predict efficient treatment measures in MDD patients.Support or Funding InformationThis research was supported by the National Key Research and Development Program of China (2018YFC0910202, 2016 YFC 1306300), the Key Basic Research Program of the Ministry of Science and Technology of China (2013FY114100), the Beijing Natural Science Foundation (7173264, 7172076), the Beijing cooperative construction project (110651103), the Beijing Normal University (11100704), the Peking Union Medical College Hospital (2016–2.27), and Beijing Biobank of Clinical Resources‐‐Mental Disorders, BBCR‐MD.

Spatio-temporal dynamics of EEG features during sleep in major depressive disorder after treatment with escitalopram: a pilot study

BackgroundPrevious studies have shown escitalopram is related to sleep quality. However, effects of escitalopram on dynamics of electroencephalogram (EEG) features especially during different sleep stages have not been reported. This study may help to reveal pharmacological mechanism underlying escitalopram treatment.MethodsThe spatial and temporal responses of patients with major depressive disorder (MDD) to escitalopram treatment were analyzed in this study. Eleven MDD patients and eleven healthy control subjects who completed eight weeks’ treatment of escitalopram were included in the final statistics. Six-channel sleep EEG signals were acquired during sleep. Power spectrum and nonlinear dynamics were used to analyze the spatio-temporal dynamics features of the sleep EEG after escitalopram treatment.ResultsFor temporal dynamics: after treatment, there was a significant increase in the relative energy (RE) of δ1 band (0.5 - 2 Hz), accompanied by a significant decrease in the RE of β2 band (20 - 30 Hz). Lempel-Ziv complexity and Co - complexity values were significantly lower. EEG changes at different sleep stages also showed the same regulation as throughout the night sleep. For spatio dynamics: after treatment, the EEG response of the left and right hemisphere showed asymmetry. Regarding band-specific EEG complexity estimations, δ1 and β2 in stage-1 and δ1 in stage-2 sleep stage in frontal cortex is found to be much more sensitive to escitalopram treatment in comparison to central and occipital cortices.ConclusionsThe sleep quality of MDD patients improved, EEG response occurred asymmetry in left and right hemispheres due to escitalopram treatment, and frontal cortex is found to be much more sensitive to escitalopram treatment. These findings may contribute to a comprehensive understanding of the pharmacological mechanism of escitalopram in the treatment of depression.

MEMORY COMPLAINTS AND DEPRESSION TREATMENT IN OLDER ADULTS

Introduction Older adults with major depression (or late-life depression) often complain about problems with thinking and memory. Some evidence suggests that subjective cognitive complaints may be a useful prognostic indicator of response to antidepressant medication. In one prior study, older adults with major depression and executive functioning complaints responded more slowly to escitalopram treatment over 12 weeks compared with older depressed adults with no executive functioning complaints. It is unclear whether the potential association between subjective cognitive complaints and treatment response generalizes to other cognitive domains and whether there is a longer-term relationship between treatment response and subjective cognitive complaints. The aim of the current study is to understand the relationship between subjective memory complaints and late-life depression treatment response at 12 weeks and one-year. The mechanism explaining the potential association between subjective cognitive complaints and treatment responses is unclear. Subjective memory complaints may represent subtle changes in objective memory test performance. Better objective story memory at baseline was associated with better depression outcomes one-year later in older adults with major depression. However, a large body of research also suggests subjective memory complaints in older adults are related to the severity of depression, anxiety, and/or personality traits (e.g., neuroticism), all factors that detrimentally influence depression treatment in older adults. Given these findings, we expected to find an association between subjective memory complaints and treatment response in late-life depression but hypothesized that the association would no longer be significant when controlling for depression severity, state anxiety, neuroticism, and objective memory performance. Methods The Neurobiology of Late-Life Depression (NBOLD) is a naturalistic longitudinal observation study of late-life depression. Upon enrollment, all patients were offered open label treatment with sertraline but this was not a requirement of participation. Instead, patients could have received other SSRIs/SNRIs and psychological treatment from non-study providers. Moreover, in some cases of mild major depression, patients may have elected not to receive treatment at all. All subjects underwent annual cognitive evaluations and depression monitoring with the Montgomery Asberg Depression Rating Scale (MADRS) as clinically indicated (and at least every three months). At baseline, subjective memory complaints were measured with the Memory Abilities Scale (MAB), state anxiety was measured with State-Trait Anxiety Inventory (STAI), and neuroticism was measured with the NEO-PI-R. Statistical Analyses: We conducted regression models testing the association between 12 week and one-year MADRS and baseline subjective memory complaints, objective memory performance (Logical Memory Delayed Recall), state anxiety, neuroticism, antidepressant usage, and relevant demographics. We tested both linear (continuous MADRS score) and logistic (yes-no presence of remission defined as MADRS Results The sample consisted of 90 patients at 12 weeks and 85 at one year. Regarding antidepressant treatment, 47.5% of LLD patients (n=57) began treatment with sertraline upon enrollment, 27.5% (n=33) were on some other SSRI and/or SNRI combination, and 25% were not receiving antidepressants. Contrary to our hypotheses, linear regression models revealed that baseline subjective memory complaints were a significant predictor of 12 week (Coefficient = -.087 +- .038, p = .025) and one-year MADRS (Coefficient = -.097 +- .039, p = .014) scores even when accounting for objective memory performance (Logical Memory Delayed Recall), state anxiety, neuroticism, antidepressant usage, and relevant demographics. Using the same covariates, subjective memory complaints also predicted remission at 12 weeks (OR[95%CI] = 1.07 (1.02, 1.11) p Conclusions Subjective memory complaints seem to be a useful indicator of depression treatment response in older adults with major depression. Notably the relationship between subjective memory complaints and treatment response was present even when accounting for other important factors shown to be related to subjective cognitive complaints and treatment outcome. Future work should investigate the biological and cognitive correlates of subjective memory complaints in older adults with major depression. This research was funded by: The research was supported by the Leo and Anne Albert Charitable Trust & NIMH Grant R01 MH108578.

Could EEG Help Predict Antidepressant Response?

Could EEG Help Predict Antidepressant Response?

Prospective testing of a neurophysiologic biomarker for treatment decisions in major depressive disorder: The PRISE-MD trial

Management of Major Depressive Disorder (MDD) might be improved by a biomarker to predict whether a selected medication is likely to lead to remission. We previously reported on a quantitative electroencephalogram-based biomarker, the Antidepressant Treatment Response (ATR) index, that integrated recordings at baseline and after one week of treatment. The present study prospectively tested whether treatment directed by the biomarker increased the likelihood of remission; we hypothesized that continued treatment with a drug predicted to lead to remission (i.e., high ATR values) would be associated with better outcomes than if the drug was predicted not to lead to remission (i.e., low ATR values). We enrolled 180 adult outpatients with unipolar MDD from the community. After one week of escitalopram treatment to determine the biomarker, stratified randomization (high vs. low ATR) was used to assign subjects to either continued escitalopram or a switch to bupropion as a blinded control condition, for seven additional weeks. For the 73 evaluable subjects assigned to continued escitalopram treatment, the remission rate was significantly higher for those in whom ATR had predicted remission versus non-remission (60.4% vs. 30.0%, respectively, p = 0.01). Accuracy was enhanced by combining 1-week depressive symptom change with ATR (68.6% vs 28.9%). This prospective validation study supports further development of the ATR biomarker, alone or together with early symptom change, to improve care by identifying individuals unlikely to remit with their current treatment, and support the decision to change treatment after one week rather than after failing a full, prolonged course of medication.

Differences in cytokines between patients with generalised anxiety disorder and panic disorder

Objective: The purpose of this study was to evaluate the differences among panic disorder (PD), generalised anxiety disorder (GAD) and controls in inflammatory cytokines. We also analysed the correlation between inflammatory cytokines and response to escitalopram in PD and GAD patients.Methods: Eighty-six patients with PD, 86 patients with GAD and 86 healthy controls were recruited for this study. All participants were, respectively, assessed for severity of anxiety and panic symptoms using the Hamilton Anxiety Rating Scale (HAMA) and the Panic Disorder Severity Scale (PDSS); all patients in the study were also assessed after 4 weeks of treatment. The serum levels of cytokines were measured using a flow fluorescence microsphere assay.Results: Both PD and GAD patients had higher serum levels of interleukin 6 (IL-6) than controls, and patients with PD showed significantly higher IL-6 than GAD patients. Significant positive correlations were found between the IFN-γ levels and the severity of anxiety in GAD patients. Higher level of IL-6 was associated with better response to escitalopram treatment in PD patients. However, the baseline levels of cytokines were not associated with treatment responses in GAD patients.Conclusion: The present findings suggest that patients with PD may have higher levels of IL-6 than GAD, and higher baseline levels of IL-6 may be a better response to escitalopram in the treatment of PD.

Acute 5-HT2C Receptor Antagonist SB-242084 Treatment Affects EEG Gamma Band Activity Similarly to Chronic Escitalopram.

Serotonin 2C receptors (5-HT2CRs) are implicated in the pathomechanism and treatment of anxiety and depression. Recently, as a new biomarker of depression, alterations in the gamma power of the electroencephalogram (EEG) have been suggested. Chronic treatment with the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram has been shown to cause sleep-wake stage-dependent alterations in gamma power. However, despite the antidepressant potency of 5-HT2CR-antagonists, there is no data available regarding the effects of selective 5-HT2CR-antagonists on gamma activity. Therefore, we investigate the acute effect of the 5-HT2CR-antagonist SB-242084 on gamma power in different vigilance stages when given in monotherapy, or in combination with chronic escitalopram treatment. We administered SB-242084 (1 mg/kg, intraperitoneally) or vehicle to EEG-equipped rats after a 21-day-long pretreatment with escitalopram (10 mg/kg/day, via osmotic minipumps) or vehicle. Frontoparietal EEG, electromyogram, and motor activity were recorded during the first 3 h of passive phase, after the administration of SB-242084. Quantitative EEG analysis revealed that acute SB-242084 increased gamma power (30–60 Hz) in light and deep slow-wave sleep, and passive wakefulness. However, in active wakefulness, rapid eye movement sleep, and intermediate stage, no change was observed in gamma power. The profile of the effect of SB-242084 on gamma power was similar to that produced by chronic escitalopram. Moreover, SB-242084 did not alter chronic escitalopram-induced effects on gamma. In conclusion, the similarity in the effect of the 5-HT2CR-antagonist and chronic SSRI on gamma power provides further evidence for the therapeutic potential of 5-HT2CR-antagonists in the treatment of depression and/or anxiety.

The relationship between plasma serotonin and kynurenine pathway metabolite levels and the treatment response to escitalopram and desvenlafaxine

IntroductionThe response of patients with major depressive disorders (MDD) to antidepressant treatments have been shown to be affected by multiple factors, including disease severity and inflammation. Increasing evidence indicates that the kynurenine metabolic pathway is activated by inflammation in MDD patients and plays a role in the pathophysiology of depression. Antidepressant treatments have been reported to affect kynurenine pathway metabolite levels as well. This study investigates differential associations between the antidepressant treatment outcome to escitalopram versus desvenlafaxine with the pre-treatment and post-treatment-changes in serotonin and kynurenine pathway metabolite levels. MethodsThe levels of serotonin and of kynurenine pathway metabolites were measured in plasma using liquid chromatography-mass spectrometry (LC-MS) in 161 currently depressed patients with MDD at baseline and after 8 weeks of treatment with either escitalopram or desvenlafaxine. Treatment response was defined conventionally by a reduction of at least 50% in the Hamilton Depression Rating Scale 21 item (HAMD-21) total score from baseline; remission was defined by reaching a post-treatment HAMD-21 score ≤7. ResultsResponse to escitalopram treatment was associated with higher baseline serotonin levels (p = 0.022), lower baseline kynurenine (Kyn)/tryptophan (Trp) ratio (p = 0.008) and lower baseline quinolinic acid (QuinA)/tryptophan (Trp) ratio (p = 0.047), suggesting a lower inflammation state. Greater improvement in depression symptoms as measured by percent change of HAMD-21 score from baseline was also associated with higher baseline serotonin levels (p = 0.033) in escitalopram treatment arm. Furthermore, remitters to escitalopram treatment showed significant increases in the kynurenic acid (KynA)/3-hydroxykynurenine (3HK) ratio after treatment (p = 0.015). In contrast, response to desvenlafaxine treatment was not associated with any metabolite analyzed. We also confirmed a previous report that plasma serotonin levels are lower in MDD patients compared to healthy controls (p = 0.004) and that the kynurenine plasma level is negatively associated with depression symptom severity (p = 0.047). ConclusionsIn MDD patients the antidepressant response to escitalopram was positively associated with baseline serotonin levels and inversely associated with activation of the kynurenine pathway. These results appear consistent with previous literature showing that biomarker evidence of inflammation is associated with lower response to antidepressants from the selective serotonin reuptake inhibitor class. Moreover, increases in the kynurenic acid (KynA)/3-hydroxykynurenine (3HK) ratio, which previously has been characterized as a neuroprotective index, were associated with full remission under escitalopram treatment.

Effect of Escitalopram on Serum GDNF and BDNF Levels and 5-HT Level of Brain Tissue of Obsessive-Compulsive Disorder Rats.

The present study aims to discuss the effect of escitalopram in glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) levels, and 5-Hydroxytryptamine (5-HT) in obsessive-compulsive disorder rats. A total of 42 rats were divided into three groups randomly: control group (n = 14), model group (n = 14) (obsessive-compulsive disorder group), and escitalopram group (n = 14) (model + obsessive-compulsive disorder group + escitalopram treatment). The open-field method was used to test the rat behavior, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum GDNF and BDNF levels. In addition, Western blot was used to determine the brain tissue protein levels of GDNF and BDNF and high-performance liquid chromatography + electrochemistry method to determine the 5-HT level of brain tissue. Visiting place was changed, rotational frequency and fixed duration enhanced in escitalopram group compared to model group (P < 0.05). Besides, GDNF and BDNF levels of serum and brain tissue were decreased in model group and escitalopram group compared to control group (P < 0.05), while GDNF and BDNF levels of serum and brain tissue were increased in escitalopram group compared to model group (P < 0.05). Moreover, the 5-HT level of brain tissue in escitalopram group was higher than that in model group (P < 0.05). Escitalopram could increase GDNF and BDNF levels and 5-HT content in serum and brain tissue in obsessive-compulsive disorder rats, which contributes to a function on the treatment of obsessive-compulsive disorder.

Use of Machine Learning for Predicting Escitalopram Treatment Outcome From Electroencephalography Recordings in Adult Patients With Depression

Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an individual patient's response to treatment could significantly reduce the burden of depression. To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression. This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment. All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment. The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%. Of the 122 participants who completed a baseline EEG recording (mean [SD] age, 36.3 [12.7] years; 76 [62.3%] female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%). These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.

An Assessment of Crosstalk between Serotonin and Dopamine Systems after Escitalopram Treatment Using LC-MS Technique with Ion-trap Analyser

The present work was aimed at developing and validating a highly sensitive analytical method to estimate the levels of monoamines from mice brain and to apply the developed method to assess the effect of escitalopram treatment on the levels of serotonin, dopamine and noradrenaline in the mouse brain. Liquid chromatography-mass spectroscopy was optimized to achieve separation of selected neurotransmitters. Method validation was performed as per the ICH guidelines. Extraction of the neurotransmitters from mice brain tissue was optimized to achieve highest recovery. In vivo study involved behavioural profile assessment after 7 d pre-treatment with escitalopram and correlating the results with monoamines levels in their brain homogenate. Behavioural profiles showed a significant (p<0.05) change in all tested parameters. These values were in agreement with the significant rise in serotonin levels (p<0.05) seen on escitalopram treatment compared to vehicle control. Along with the elevation in serotonin levels, a significant increase in levels of dopamine and a mild increase in noradrenaline levels was observed due to the possible crosstalk between the neurotransmission pathways. Liquid chromatography-mass spectroscopy method was developed and validated for estimation of brain neurotransmitters which revealed a crosstalk resulting in the elevation in levels of various monoamines after escitalopram treatment.

Effect of antidepressants for cessation therapy in betel-quid use disorder: a randomised, double-blind, placebo-controlled trial.

More than one-half of betel-quid (BQ) chewers have betel-quid use disorder (BUD). However, no medication has been approved. We performed a randomised clinical trial to test the efficacy of taking escitalopram and moclobemide antidepressants on betel-quid chewing cessation (BQ-CC) treatment. We enrolled 111 eligible male BUD patients. They were double-blinded, placebo-controlled and randomised into three treatment groups: escitalopram 10 mg/tab daily, moclobemide 150 mg/tab daily and placebo. Patients were followed-up every 2 weeks and the length of the trial was 8 weeks. The primary outcome was BQ-CC, defined as BUD patients who continuously stopped BQ use for ⩾6 weeks. The secondary outcomes were the frequency and amount of BQ intake, and two psychological rating scales. Several clinical adverse effects were measured during the 8-week treatment. Intention-to-treat analysis shows that after 8 weeks, two (5.4%), 13 (34.2%) and 12 (33.3%) of BUD patients continuously quit BQ chewing for ⩾6 weeks among placebo, escitalopram, moclobemide groups, respectively. The adjusted proportion ratio of BQ-CC was 6.3 (95% CI 1.5-26.1) and 6.8 (95% CI 1.6-28.0) for BUD patients who used escitalopram and moclobemide, respectively, as compared with those who used placebo. BUD patients with escitalopram and moclobemide treatments both exhibited a significantly lower frequency and amount of BQ intake at the 8th week than those with placebo. Prescribing a fixed dose of moclobemide and escitalopram to BUD patients over 8 weeks demonstrated treatment benefits to BQ-CC. Given a relatively small sample, this study provides preliminary evidence and requires replication in larger trials.

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.

Association Between Side Effects and Blood microRNA Expression Levels and Their Targeted Pathways in Patients With Major Depressive Disorder Treated by a Selective Serotonin Reuptake Inhibitor, Escitalopram: A CAN-BIND-1 Report.

IntroductionAntidepressant drugs are effective therapies for major depressive disorder; however, they are frequently associated with side effects. Although there is some evidence for a relationship between genetic variation and side effects, little is known regarding the role of dynamic molecular factors as moderators of side effects. The aim of this study was to assess microRNA (miRNA) changes associated with side effects during escitalopram treatment and their downstream effects on target gene expression.MethodsA total 160 patients with major depressive disorder from the CAN-BIND-1 cohort were included. Side effects were assessed with the Toronto Side Effect Scale after 2 weeks of treatment with escitalopram. We assessed the relationship between side effects and changes in peripheral expression of miRNAs between baseline and week 2. For miRNA whose expression changed, we used target prediction algorithms to identify putative messenger RNA (mRNA) targets and assessed their expression.ResultsNausea was experienced by 42.5% of patients. We identified 45 miRNAs whose expression changed on initiation of escitalopram treatment, of which 10 displayed a negative association with intensity of nausea (miR15b-5p, miR17-5p, miR20a-5p, miR20b-5p, miR103a-3p, miR103b, miR106a-5p, miR182-5p, miR185-5p, and miR660-5p). Additionally, we found negative associations between 4 microRNAs (miR20a-5p, miR106a-5p, miR185-5p, miR660-5p) and mRNA targets. The expression of the miR185-5p target, CAMK2δ was significantly decreased [log 2 mean = −0.048 (0.233)] between weeks 0 and 2 (P = .01)].ConclusionsWe identified an overexpression of miR185-5p during escitalopram treatment of major depressive disorder, which was negatively associated with intensity of nausea, and identified a potential mRNA target that may mediate this effect.

Cognitive changes after tDCS and escitalopram treatment in major depressive disorder: Results from the placebo-controlled ELECT-TDCS trial

BackgroundCognitive deficits in major depressive disorder (MDD) are associated with low quality of life and higher suicide risk. Antidepressant drugs have modest to null effects in improving such deficits. Therefore, we investigated the cognitive effects of transcranial direct current stimulation (tDCS), which is a promising antidepressant non-pharmacological intervention, in MDD. MethodsAn exploratory analysis on cognitive performance was conducted in 243 depressed patients from the Escitalopram vs. Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS), a sham-controlled study comparing the efficacy of tDCS vs. escitalopram. A neuropsychological battery was applied at baseline and endpoint (10 weeks of treatment) to create composite cognitive scores (processing speed, working memory, and verbal fluency). Linear mixed regression models were used to evaluate changes according to intervention groups, adjusted for confounding variables (age, years of schooling, gender, and benzodiazepine use) and depression improvement. ResultsNo cognitive deterioration was observed in any group. Patients receiving tDCS presented reduced practice gains compared to placebo in processing speed. In patients receiving escitalopram vs. placebo and in the subgroup of clinical responders (>50% depression improvement from baseline), those receiving tDCS vs. placebo presented increased performance in verbal fluency. No significant differences between tDCS and escitalopram groups were detected. LimitationsAbsence of healthy controls. ConclusionPrefrontal tDCS did not lead to cognitive deficits in depressed patients, although it reduced practice effects in processing speed. tDCS responders presented increased performance in verbal fluency. Further investigation of tDCS cognitive effects in depression is warranted.

The impact of oral escitalopram treatment on the function of retinal interneurons in the rat model of retinal ischemia – a pilot study

AbstractPurposeTo evaluate the impact of oral treatment with SSRI – escitalopram (EC) on the function of interneurons (IN) assessed in electroretinography.MethodsSix Long Evans rats were treated orally with SSRI‐escitalopram (n=3) or phosphate buffered saline‐PBS (n=3) for 6 weeks daily. After 4 weeks transient elevation of intraocular pressure (IOP) was inducted in the right eye of every rat in order to induce retinal ischemia (IC). Electroretinography (ERG) was performed using Celeris device and oscillatory potentials were analysed (OPs) in 4 time points ‐ before drug administration, before IC induction and 7 &amp; 14 days after it. After 6 weeks rats were sacrificed, retinas were isolated in order to conduct the histological assessment and cell counts. Western Blot analysis was performed in order to assess BDNF and connexin 36 content in retinas and brains.ResultsThe mean peak IOP was 24 mmHg in the right eye and 12 mmHg in the left eye and was similar in treated and control groups. In both groups no loss of RGC density was noted between the eye with induced IC and the healthy one (80 ± 31 vs 76 ± 20 cells/visual field for EC and 55 ± 10 vs 55 ± 11 for PBS; p &gt; 0.05). In the functional measurements in the EC group amplitudes of all scotopic OPs (OP1‐5) were significantly higher 14 days after IC induction when compared to control group (p &lt; 0.05), where deep disturbance of IN function was observed, specifically for OP2‐4, expressed in significant reduction of OP amplitudes (p &lt; 0.05). Similar changes were not observed in photopic conditions.ConclusionsOral treatment with EC prevents desynchronization of retinal IN function during ischemic conditions in a rat. Observations presented above may become crucial for new therapeutic methods for vascular pathologies of the retina.

Predicting escitalopram monotherapy response in depression: The role of anterior cingulate cortex.

Neuroimaging biomarkers of treatment efficacy can be used to guide personalized treatment in major depressive disorder (MDD). Escitalopram is recommended as first‐line therapy for MDD and severe depression. An interesting hypothesis suggests that the reconfiguration of dynamic brain networks might provide important insights into antidepressant mechanisms. The present study assesses whether the spatiotemporal modulation across functional brain networks could serve as a predictor of effective antidepressant treatment with escitalopram. A total of 106 first‐episode, drug‐naïve patients and 109 healthy controls from three different multicenters underwent resting‐state functional magnetic resonance imaging. Patients were considered as responders if they had a reduction of at least 50% in Hamilton Rating Scale for Depression scores at endpoint (>2 weeks). Multilayer modularity framework was applied on the whole brain to construct features in relation to network dynamic characters that were used for multivariate pattern analysis. Linear soft‐threshold support vector machine models were used to separate responders from nonresponders. The permutation tests demonstrated the robustness of discrimination performances. The discriminative regions formed a spatially distributed pattern with anterior cingulate cortex (ACC) as the hub in the default mode subnetwork. Interestingly, a significantly larger module allegiance of ACC was also found in treatment responders compared to nonresponders, suggesting high interactivities of ACC to other regions may be beneficial for the recovery after treatment. Consistent results across multicenters confirmed that ACC could serve as a predictor of escitalopram monotherapy treatment outcome, implying strong likelihood of replication in the future.