Escitalopram Treatment Research Articles

The Effect of Adding Agomelatine to Escitalopram in the Treatment of Major Depressive Disorder

Major Depressive Disorder (MDD) is a psychiatric illness that imposes a high cost on the patient and the community. Over the past few decades, a variety of treatments have been used to treat depression. One of the most common treatments for depression is medication. Today, specific serotonin reuptake inhibitors are the first line of treatment for major depression. Another drug that has been considered in the treatment of depression is agomelatine.Objective of this study was to evaluate the effect of adding agomelatine to Escitalopram in treatment of major depressive disorder.Materials and methods. This study was a double-blind randomized clinical trial with before and after designs (b and a). In this study, 70 patients with MDD referred to psychiatric clinics affiliated with Yazd University of Medical Sciences were studied. Patients were randomly divided into two groups of 35 patients (agomelatine + Escitalopram and Escitalopram + placebo) and were treated for 12 weeks. Depression Scale was the Hamilton Depression Inventory and was assessed before treatment, 1, 2, and 3 months after treatment. Variables such as gender, age, marital status, level of education, occupation, and duration of illness were also collected. The data were entered into SPSS version 18 software and analyzed using statistical tests.Results. Of the 70 patients studied, 31 (44.3%) were male and 39 (55.7%) were female. There was not significant difference between gender distribution (p=0.810), marital status(p=0.789), job (p=0.651) and educational level (p=0.794). Also, no significant difference was found between the mean variables: age (p=0.563) and duration of depression (p=0.958). There was a statistically significant difference between the mean score of depression 2 months after treatment (p=0.10) and 3 months after treatment (p=0.023) in the two groups. Also the mean depression score after treatment compared to before, was significantly lower in both groups (p=0.000). Also, no significant difference was found between the frequency of drug side effects in the two groups (p=0.970).Conclusion. Adding agomelatine to Escitalopram is more effective than mood-boosting depression as a result of depression or depressive disorder alone.Future researchers in the field of MDD treatment could consider investigating the long-term effects and comparative efficacy of combining agomelatine with other antidepressants beyond Escitalopram to further enhance treatment outcomes for patients with MDD.

Serotonin transporter 5-HTTLPR polymorphism and escitalopram treatment response in patients with major depressive disorder

BackgroundThere is no doubt that genetic factors have the potential to predict the therapeutic outcomes of antidepressants in patients with major depressive disorder (MDD). This study investigated the association between genetic variants involved in serotonin signaling and brain-derived neurotrophic factor (BDNF) with the response to escitalopram treatment in patients with MDD. We focused on examining the influence of 5-HTTLPR (ins/del), HTR2A rs9316233, BDNF rs962369, CYP2C19 and CYP2D6 on the clinical response to escitalopram.MethodsThe patients were recruited from outpatient psychiatric clinics in Košice between 2020 and 2022. Patients received escitalopram for 12 weeks at a fixed dose of 10 mg daily. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 21-item Hamilton Depression Rating Scale (HAMD-21).ResultsAt the end of week 12, 57 (65%) patients were defined as responders to escitalopram treatment, while 31 (35%) patients were non-responders. Genotyping revealed that carriers of the short allele (S) of 5-HTTLPR exhibit a significantly lower therapeutic response to escitalopram measured by HAMD-21 than the long allele (L) carriers (p = 0.01). Adjusting for CYP2C19 and CYP2D6 metabolizer genotypes did not modify the observed relationship between 5-HTTLPR and treatment response. No significant associations were found for HTR2A rs9316233 or BDNF rs962369 variants and the treatment response.ConclusionsThese findings underscore the utility of 5-HTTLPR genotyping in guiding escitalopram therapy for MDD patients. Further research with larger cohorts is warranted to validate these results and elucidate additional genetic determinants of antidepressant efficacy.

The impact of sleep disturbances on treatment efficacy and prognosis in patients with depressive and anxiety disorders.

Little was known about the relationship between sleep disturbances and depressive and anxiety disorders, as well as the efficacy of treatment regimens. During 2021 to 2023, a total of 417 participants were screened by Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA-14) for psychological status, and Pittsburgh sleep quality index (PSQI) assessment. 409 participants were finally enrolled, of which 188 (45.97%) were suffered from sleep disorders. All participants were received polysomnography (PSG) followed by six-week pharmacological treatment of escitalopram and zopiclone, and finally assessed by HAMD-17 and HAMA-14 for treatment efficacy. PSG monitoring indicated that participants with depression experienced prolonged rapid eye movement sleep latency (REMSL) and increased wakefulness after sleep onset (WASO) (P=0.030 and P=0.002, respectively). Those with anxiety disorders demonstrated a significantly higher percentage of non-rapid eye movement sleep (NREM%) and reduced WASO (P=0.013 and P=0.001, respectively). After six-weeks pharmacological treatment, participants with or without sleep disorders exhibited with similar efficacy outcomes of depression and anxiety disorders (P>0.05). However, every point of PSQI increment at baseline would decrease 0.78 and 0.85 times of probability of effective pharmacological treatment of depression and anxiety disorders. Moreover, participants with both effective outcomes of depression and anxiety disorders were found significant shorter sleep onset latency (SOL) (P<0.001). The insights gained underscore the necessity of considering sleep disturbances in enhancing the overall effectiveness of pharmacological treatments for depression and anxiety disorders.

Modulation of neural oscillations in escitalopram treatment: a Canadian biomarker integration network in depression study

Current pharmacological agents for depression have limited efficacy in achieving remission. Developing and validating new medications is challenging due to limited biological targets. This study aimed to link electrophysiological data and symptom improvement to better understand mechanisms underlying treatment response. Longitudinal changes in neural oscillations were assessed using resting-state electroencephalography (EEG) data from two Canadian Biomarker Integration Network in Depression studies, involving pharmacological and cognitive behavioral therapy (CBT) trials. Patients in the pharmacological trial received eight weeks of escitalopram, with treatment response defined as ≥ 50% decrease in Montgomery–Åsberg Depression Rating Scale (MADRS). Early (baseline to week 2) and late (baseline to week 8) changes in neural oscillation were investigated using relative power spectral measures. An association was found between an initial increase in theta and symptom improvement after 2 weeks. Additionally, late increases in delta and theta, along with a decrease in alpha, were linked to a reduction in MADRS after 8 weeks. These late changes were specifically observed in responders. To assess specificity, we extended our analysis to the independent CBT cohort. Responders exhibited an increase in delta and a decrease in alpha after 2 weeks. Furthermore, a late (baseline to week 16) decrease in alpha was associated with symptom improvement following CBT. Results suggest a common late decrease in alpha across both treatments, while modulatory effects in theta may be specific to escitalopram treatment. This study offers insights into electrophysiological markers indicating a favorable response to antidepressants, enhancing our comprehension of treatment response mechanisms in depression.

Intermittent escitalopram treatment and reactive aggression in women with premenstrual irritability and anger: A crossover study

BackgroundSelective serotonin reuptake inhibitors (SSRI) are the primary treatment for premenstrual mood symptoms and particularly effective in reducing reactive aggression in the forms of irritability and anger.The present study examined whether behavioral responses in laboratory measures of reactive aggression are influenced by medication with the SSRI escitalopram in women reporting high levels of premenstrual irritability/anger. MethodsParticipants (N = 34) rated the cardinal mood symptoms of premenstrual dysphoric disorder over three menstrual cycles. During the second and third cycles, participants received escitalopram (20 mg) or placebo in a single-blind, cross-over design. In the luteal phase of the intervention cycles, participants completed two aggression tasks: The Anger-Infused Ultimatum Game (AI-UG) and the Point Subtraction Aggression Paradigm (PSAP). Additionally, they rated expression and control of anger using the State-Trait Anger Expression Inventory-2 (STAXI-2) once in the luteal phase and once in the follicular phase. ResultsWhile irritability/anger was reduced in the treatment (vs. placebo) cycle, no effect of escitalopram was detected in the PSAP. Escitalopram decreased reactive aggressive behavior in the AI-UG but only for a subset of participants who experienced a sharp premenstrual rise in outwardly expressed anger and/or did not experience a premenstrual rise in inwardly expressed anger. LimitationsThe participants' symptoms were based on the severity of only premenstrual irritability/anger, limiting the generalizability to the broader group of PMDD patients. ConclusionThe results suggest that the behavioral consequences of severe premenstrual irritability/anger are not easily captured by traditional measures of reactive aggression and underline the importance of considering individual differences in symptom expression.

Positive Psychotic Symptoms after Escitalopram Treatment in a Female Adolescent with Peroxisome Spectrum Disorder Due to PEX-6 Gene Mutation

Introduction: In this case report, we present positive psychotic symptoms that developed after low-dose (5 mg/day) escitalopram treatment in a 16-year-old female adolescent with a peroxisome biogenesis disorder. Case presentation: Two weeks after starting escitalopram treatment for depression, the patient experienced vomiting attacks several times a day. About 2-3 days after the attacks began, the family stopped administering escitalopram. Five days after the onset of vomiting and 2-3 days after stopping escitalopram, the patient developed visual and auditory hallucinations and persecutory delusions. During the patient's follow-up period, the diversity of her hallucinations and delusions increased. When olanzapine treatment was gradually increased to 20 mg/day, the patient's psychotic symptoms disappeared. Conclusion: We discuss serotonin syndrome, drug-induced bipolar disorder, and psychotic disorder in the differential diagnosis. We believe that this case report is valuable as it is the first in the literature regarding the development of positive psychotic symptoms after SSRI use in a patient with a peroxisome biogenesis disorder.

DNA methylation of serotonin genes as predictive biomarkers of antidepressant treatment response

Selective serotonin reuptake inhibitors (SSRI) are frequently ineffective in treating depressive episodes and biomarkers are needed to optimize antidepressant treatment outcomes. DNA methylation levels of serotonin transporter (SLC6A4) and tryptophan hydroxylase 2 genes (TPH2) have been suggested to predict antidepressant clinical outcomes but their applicability remains uncertain. In this study, we: 1) evaluated SLC6A4/TPH2 methylation biomarker potential for predicting clinical outcomes after escitalopram treatment; 2) evaluated whether changes in SLC6A4/TPH2 methylation are informative of treatment mechanisms. We used a cohort of 90 unmedicated patients with major depressive disorder that were part of a 12-week open-label longitudinal trial and compared our observations with previous findings. Depressive symptoms were measured at baseline and after 8 and 12 weeks of treatment using the Hamilton Depression Rating Scale (HAMD6/17). We found an association between baseline TPH2 methylation and both clinical response (β:3.43; p = 0.01; 95 % CI:[0.80; 6.06]) and change in depressive symptoms after 8 weeks (β:−45.44; p = 0.01; 95 %CI:[− −78.58; −12.30]). However, we found no evidence for predictive value of any gene (TPH2 AUC: 0.74 95 % CI:[0.42;0.79]; SLC6A4: AUC: 0.61; 95 % CI: [0.48–0.78]). Methylation levels changed at the trend level for CpG sites of SLC6A4 and TPH2 over the course of 12 weeks of treatment. In addition, similar to previous observations, we found a trend for an association between methylation of SLC6A4 CpG2 (chr17:30,236,083) and HAMD17 change after 12 weeks. Our findings suggest that although TPH2 and SLC6A4 methylation may be informative of antidepressant treatment outcome, they are unlikely to prove useful as clinical predictor tools.

Impact of comorbid sleep-disordered breathing on escitalopram treatment in patients newly diagnosed with generalized anxiety disorder: A 12-week prospective observational study

We aimed to evaluate the presence of sleep-disordered breathing (SDB) in generalized anxiety disorder (GAD) patients and its impacts after 12-week of escitalopram treatment. In this prospective observational study, GAD patients were followed up to determine whether comorbid SDB affects their treatment response. They underwent a home sleep apnea test (HSAT), and oxygen desaturation index ≥5 was considered indicative of SDB. All participants were treated with escitalopram 5 mg in the first 2 weeks and 10 mg in the remaining 10 weeks. They underwent assessments of heart rate variability and completed questionnaires for sleep, mood, attention, and daytime sleepiness on the day of enrollment, and 2 weeks, 4 weeks, and 12 weeks later. A total of 45 GAD participants (mean age, 56.2 years) were included in the study. Of these, 53.3% had comorbid SDB. Participants with GAD and SDB had higher baseline Beck Anxiety Inventory (BAI) and STOP-BANG scores. Both groups of participants with GAD showed overall improvement in anxiety, depression, and insomnia symptoms after 12 weeks of escitalopram treatment. Additionally, there were no statistically significant differences in the changes in BAI, Beck Depression Inventory, and Epworth Sleepiness Scale scores between the two groups at the Week 2, Week 4, and Week 12 assessments compared to baseline. However, the GAD group with comorbid SDB seemed to have a lower tendency for improvement in depressive symptoms than the group with non-comorbid SDB. Compared with the GAD group without comorbid SDB, the GAD group with comorbid SDB exhibited more severe anxiety symptoms at baseline and tended to show less improvement in depressive symptoms after 12 weeks of escitalopram treatment.

Contribution of resting-state functional connectivity of the subgenual anterior cingulate to prediction of antidepressant efficacy in patients with major depressive disorder

This study investigated how resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) predicts antidepressant response in patients with major depressive disorder (MDD). Eighty-seven medication-free MDD patients underwent baseline resting-state functional MRI scans. After 12 weeks of escitalopram treatment, patients were classified into remission depression (RD, n = 42) and nonremission depression (NRD, n = 45) groups. We conducted two analyses: a voxel-wise rsFC analysis using sgACC as a seed to identify group differences, and a prediction model based on the sgACC rsFC map to predict treatment efficacy. Haufe transformation was used to interpret the predictive rsFC features. The RD group showed significantly higher rsFC between the sgACC and regions in the fronto-parietal network (FPN), including the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL), compared to the NRD group. These sgACC rsFC measures correlated positively with symptom improvement. Baseline sgACC rsFC also significantly predicted treatment response after 12 weeks, with a mean accuracy of 72.64% (p < 0.001), mean area under the curve of 0.74 (p < 0.001), mean specificity of 0.82, and mean sensitivity of 0.70 in 10-fold cross-validation. The predictive voxels were mainly within the FPN. The rsFC between the sgACC and FPN is a valuable predictor of antidepressant response in MDD patients. These findings enhance our understanding of the neurobiological mechanisms underlying treatment response and could help inform personalized treatment strategies for MDD.

Psychiatric assessment and therapy in an adolescent with ALG6-CDG: a six-month follow-up case report.

ALG6-congenital disorder of glycosylation (ALG6-CDG) is a complex of rare inherited disorders caused by mutations in the ALG6 gene, which encodes the α-1,3-glucosyltransferase enzyme required for N-glycosylation. ALG6-CDG affects multiple systems and exhibits clinical heterogeneity. Besides developmental delays and neurological signs and symptoms, behavioral and psychological symptoms are also an important group of clinical features of ALG6-CDG. Here, we present the case of a 17-year-old Chinese girl with ALG6-CDG who first visited the psychiatric department with apathy, language reduction, and substupor symptoms. The psychiatric assessments and treatment processes performed are described and discussed in this report. During diagnostic process, we found a novel mutation, c.849delT, in ALG6 by whole-exome sequencing. The patient's symptoms improved with escitalopram and risperidone treatment. However, above a certain dosage, she was sensitive to extrapyramidal side effects. This study accumulates clinical experience for diagnosing and treating ALG6-CDG and improves our understanding of this rare genetic disorder.

A target trial emulation comparing the antidepressant effectiveness of selective serotonin reuptake inhibitors (SSRIs) highlighting the importance of patent-related confounding by indication.

The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram. To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice. We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication. We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events. Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.

CYP2C19 polymorphisms on escitalopram treatment outcome in South Indian population with major depressive disorder

Various CYP2C19-mediated metabolizer groups may arise as a result of inter-individual variability, which potentially influences the efficacy and safety of escitalopram. Hence, it is crucial to establish a comprehensive collection of information relevant to each phenotype regarding the efficacy and tolerability of therapy. This will enable psychiatrists to make optimal decisions for individual patients. The aim of the study: The aim of this study is to classify MDD patients into various CYP2C19 metabolizer groups and to determine the association between phenotype and treatment outcome. Materials and Methods: The study enrolled 119 escitalopram monotherapy-treated MDD patients aged 18–58. MADRS, HDRS-17, and CGI were used to measure efficacy at baseline, weeks 4, 8, and 12. Safety and tolerability outcomes were examined from occurring ADRs. Clinical outcomes were compared among phenotypes based on changes in HDRS-17 and CGI scores from week 4 to week 12. Results: Subjects were categorized by CYP2C19 genotype: 20 poor (PM), 64 intermediate (IM), 24 extensive (EM), and 11 ultra-rapid (UM) metabolizers. Response and remission occurred in 67.2 % and 26.8 % of the 119 subjects at the end of the 12th week of the study. The response rate in PM was much lower (21.6 %) compared to EM. There were 312 adverse drug reactions (ADRs), and 88 (73.94 %) individuals had at least one. In safety data, nervousness was the most common ADR among the four groups 66 (55.4 %), followed by decreased appetite 48 (40.3 %). There were no severe ADRs. Men had more ADRs than women. Conclusion: CYP2C19 genotyping may help personalize escitalopram medication. The study found that the reduced ability of PM to metabolize escitalopram is probably associated with the decreased efficacy and tolerance shown in PM compared to EM and IM. The relationship between metabolizer status and treatment response followed the anticipated direction. Our findings should guide future clinical studies that include pharmacokinetic assessments

Integrative Genetic Variation, DNA Methylation, and Gene Expression Analysis of Escitalopram and Aripiprazole Treatment Outcomes in Depression: A CAN-BIND-1 Study.

Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19, CYP2D6, CYP3A4, and ABCB1, and its effect on these outcomes. The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects. Eleven cis-SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain (q=0.027) and serum concentrations of ESCadj (q<0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESCadj concentrations. CITs did not indicate that these effects were epigenetically mediated. These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment. Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.

A genome-wide association study of escitalopram treatment outcomes in patients with major depressive disorder

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e − 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e − 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression.

Atypical Brain Aging and Its Association With Working Memory Performance in Major Depressive Disorder

BackgroundPatients with major depressive disorder (MDD) can present with altered brain structure and deficits in cognitive function similar to those seen in aging. However, the interaction between age-related brain changes and brain development in MDD remains understudied. In a cohort of adolescents and adults with and without MDD, we assessed brain aging differences and associations through a newly developed tool that quantifies normative neurodevelopmental trajectories. MethodsA total of 304 participants with MDD and 236 control participants without depression were recruited and scanned from 3 studies under the Canadian Biomarker Integration Network for Depression. Volumetric data were used to generate brain centile scores, which were examined for 1) differences between participants with MDD and control participants; 2) differences between individuals with versus without severe childhood maltreatment; and 3) correlations with depressive symptom severity, neurocognitive assessment domains, and escitalopram treatment response. ResultsBrain centiles were significantly lower in the MDD group than in the control group. Brain centile was also significantly correlated with working memory in the control group but not the MDD group. No significant associations were observed between depression severity or antidepressant treatment response and brain centiles. Likewise, childhood maltreatment history did not significantly affect brain centiles. ConclusionsConsistent with previous work on machine learning models that predict brain age, brain centile scores differed in people diagnosed with MDD, and MDD was associated with differential relationships between centile scores and working memory. The results support the notion of atypical development and aging in MDD, with implications for neurocognitive deficits associated with aging-related cognitive function.

Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder

ObjectiveThe purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD).MethodsSeventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment.ResultsAt baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01).ConclusionsThe results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.

Association between escitalopram dose personalisation based on quantification of drug plasma levels and the outcome of escitalopram treatment

IntroductionGiven the negative impact of anxiety and depression on society and the shortage of new antidepressants, it is of paramount importance to make the best use of available treatment options. Therapeutic drug monitoring (TDM) in escitalopram treatment can potentially be clinically useful, as underexposed patients show reduced efficacy of escitalopram treatment and as adverse drug reactions (ADRs) of escitalopram are dose-dependent.ObjectivesThis prospective cohort study aimed to investigate whether escitalopram treatment efficacy or safety are associated with escitalopram dose adjustment based on TDM readouts.Methods89 included patients aged between 15 and 65 years who suffered from depression were enrolled in the study before starting treatment with escitalopram. Patients were assessed one day before starting treatment with the recommended dose of 10 mg/day escitalopram (baseline, visit 0) and at follow-up after four and eight weeks. Dose adjustment at four-week follow-up was based on the measured escitalopram plasma level two weeks after treatment initiation; patients who required dose increase to 15 or 20 mg/day comprised comparator group, patients who did not required dose increase comprised control group, while patients who did not reach optimal exposure at eight-week follow-up were characterized as non-compliers. Treatment efficacy was approximated by the relative change on the Hamilton Depression Rating Scale (HAMD), while safety was approximated based on the changes on the Scandinavian UKU side effect rating scale and ECG readouts. Changes in HAMD, UKU score and QTc interval were compared between groups by one-way ANOVA or chi-square tests.ResultsCompared to baseline, significant reductions in HAMD scores of 36% (95%CI, 30%-43%) and 53% (95%CI, 47%-60%) were observed at four- and eight-week follow-up, respectively; however, there were no significant differences between groups (p &gt; 0.1). In the groups adjusted to 15 and 20 mg, 15/26 and 19/33 patients, respectively, reported adverse effects, compared with 6/17 patients in the control group and 6/13 in the non-complier group (p&gt;0.1). A significant mean QTc prolongation of 6.40 ms (95%CI, 3.27-9.53) was observed between the baseline and eight-week follow-up (p=0.0013), without significant differences in QTc interval prolongation between groups (p &gt; 0.1).ConclusionsEscitalopram dose adjustment resulted in optimal drug exposure and solid treatment response in the majority of patients; however, no differences in efficacy were found between the patients who required dose adjustments, the ones who did not, and the ones who ultimately did not achieve optimal exposure. In addition, the selective increase of the dose to the patients who did not reach optimal drug exposure on the recommended dose of 10 mg/day did not lead to significant increase in adverse drug reactions and QTc prolongation.Disclosure of InterestNone Declared

Schizoaffective Disorder and Parkinson’s Disease: a case report

IntroductionWe present the case of a patient with schizoaffective disorder and Parkinson’s disease (PD), requiring treatment adjustment, with the use of high doses of quetiapine for the treatment of psychotic symptomatology.ObjectivesThe aim is to briefly review the treatment of dopaminergic psychosis in the elderly.Methods Patient aged 86 years, institutionalised, presenting severe episodes of behavioural alteration, high anxiety and delusions of harm, together with auditory and visual hallucinations. As relevant physical history, the patient has AHT, aortic insufficiency, and bladder cancer operated on in 2012. As psychiatric history of interest, the patient has been diagnosed since his 30s with schizoaffective disorder, Parkinson’s disease and moderate-severe cognitive impairment secondary to the previous two.As usual treatment, in addition to anticoagulation and antihypertensive therapy, the patient has been receiving L-dopa for his PD for years, antidepressant treatment with escitalopram 10mg, haloperidol 80 drops a day, divided into three doses, and lormetazepam 2mg as a hypnotic.In addition to the symptoms described above, the patient had episodes of confusional features, as well as marked stiffness in the cogwheel and significant gait disturbance, having suffered several falls without serious repercussions.Results Due to the comorbid neurological pathology, it was decided to progressively modify the treatment, withdrawing the benzodiazepine due to the risk of confusional disorder and replacing it with trazodone. Antipsychotic treatment was gradually replaced by extended-release quetiapine, reaching a maximum dose of 800mg. Likewise, escitalopram treatment is replaced by sertraline.With this adjustment, there was an improvement in the psychotic symptoms, as well as in the anxious symptoms. Episodes of distress are NOT observed, and the patient’s functionality improves, allowing him/her to participate in daily activities, both cognitive stimulation and physiotherapy.ConclusionsThe Spanish Society of Psychogeriatrics recommends that before using antipsychotics, it is advisable to first treat the underlying potentially treatable causes (pain, infections, toxic effects of drugs…), assess non-pharmacological interventions and always, if the use of antipsychotics is required, assess the risk-benefit ratio.In relation to the above, it is not surprising that in the elderly, the use of second-generation antipsychotics is recommended in the first place, as opposed to the classical ones. The latter are only recommended in emergency situations where an almost immediate effect is required.For dopaminergic psychosis, there are only controlled trials with clozapine. However, due to prescribing difficulties, aripiprazole or quetiapine is recommended in the first instance.Disclosure of InterestNone Declared

Unraveling the potential of Morinda officinalis oligosaccharides as an adjuvant of escitalopram in depression treatment and exploring the underlying mechanisms

Ethnophamacological relevanceMorinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. Aim of the studyWe aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. Materials and methodsDepressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors’ mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. ResultsMOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. ConclusionOur results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.