Antidepressant Treatment In Patients Research Articles

Habenular volume changes after venlafaxine treatment in patients with major depression.

Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement. Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant-free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment. A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness. Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes.

Validation of the predictive value of BDNF -87 methylation for antidepressant treatment success in severely depressed patients—a randomized rater-blinded trial

BackgroundBrain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE).MethodsThe BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study’s main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE.Ethics and disseminationThe trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals.Trial registrationGerman Clinical Trial Register DRKS00032503. Registered on 17 August 2023.

Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms

Objective: Depression is a mood disorder characterized by a set of emotional, cognitive, physical and behavioral symptoms. Low response rate to antidepressant treatment in patients with depression, late onset of action, side effects due to long-term drug use, and pharmacogenetic variations limit the effectiveness and tolerability of these drugs and lead to compliance problems in patients. Therefore, studies on the discovery and development of new antidepressant drugs continue, and molecules of natural origin are becoming the focus of attention of researchers. Tangeretin, which is commonly found in citrus peels and has a pentamethoxyflavone structure, is an important member of flavonoids. Since it lacks a glycoside structure, it is easily absorbed from the intestines and can easily pass through the blood-brain barrier due to its lipophilic structure. Previous studies indicating that tangeretin may be effective on the central nervous system suggest that it may be possible for this phytochemical to have an effect on mood. Based on this idea, this study aimed to investigate the possible antidepressant-like effects of tangeretin and to elucidate the pharmacological mechanisms mediating this effect. Methods: Male Balb/c mice of the same age, weighing 30-35 g, were used for the experiments. The antidepressant-like effect of tangeretin (10, 20 ve 40 mg/kg, p.o.) was examined by tail suspension and modified forced swimming tests, while its effect on the motor coordination of experimental animals was evaluated using the Rota-rod method. Results: The data obtained revealed that doses of 10 and 20 mg/kg tangeretin decreased the immobility time of mice in tail suspension test and immobility number of mice in modified forced swimming tests compared to control animals not receiving tangeretin. These findings indicated that tangeretin showed an antidepressant-like activity comparable to the reference drug fluoxetine (30 mg/kg) when administered at doses of 10 and 20 mg/kg. Tangeretin, at the same doses, did not alter the climbing number of mice in modified forced swimming tests, but significantly increased their swimming number. The 40 mg/kg dose of this flavonoid did not cause a statistically significant effect in either test. While α-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis; 100 mg/kg i.p.) and ondansetron (a 5-HT3 receptor antagonist; 0.3 mg/kg i.p.) pretreatments did not change the antidepressant-like activity induced by 20 mg/kg dose of this flavonoid in the tail suspension tests; pretreatment of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis; 100 mg/kg i.p., administered for 4-consecutive days), NAN-190 (a 5-HT1A receptor antagonist; 0.5 mg/kg i.p.) and ketanserin (a 5-HT2A/2C receptor antagonist; 1 mg/kg i.p.), reversed this activity. These findings indicated that tangeretin has antidepressant-like activity mediated by the serotonergic system and that 5-HT1A and 5-HT2A/5-HT2C serotonergic receptor subtypes participate in this effect. Conclusion: The findings of this study suggest that tangeretin may be a useful drug candidate in the treatment of depression. However, it is clear that for tangeretin to be considered an antidepressant agent, the antidepressant-like activity presented in this preclinical study must be confirmed by well-designed clinical studies conducted on various groups of patients with depressive disorders.

Machine Learning Prediction of Quality of Life Improvement During Antidepressant Treatment of Patients With Major Depressive Disorder: A STAR*D and CAN-BIND-1 Report.

Machine Learning Prediction of Quality of Life Improvement During Antidepressant Treatment of Patients With Major Depressive Disorder: A STAR*D and CAN-BIND-1 Report.

Prediction of Early Antidepressant Efficacy in Patients with Major Depressive Disorder Based on Multidimensional Features of rs-fMRI and P11 Gene DNA Methylation: Prédiction de l'efficacité précoce d'un antidépresseur chez des patients souffrant du trouble dépressif majeur d'après les caractéristiques multidimensionnelles de la méthylation de l'ADN du gène P11 et de la IRMf-rs.

This study established a machine learning model based on the multidimensional data of resting-state functional activity of the brain and P11 gene DNA methylation to predict the early efficacy of antidepressant treatment in patients with major depressive disorder (MDD). A total of 98 Han Chinese MDD were analysed in this study. Patients were divided into 51 responders and 47 nonresponders according to whether the Hamilton Depression Rating Scale-17 items (HAMD-17) reduction rate was ≥50% after 2 weeks of antidepressant treatment. At baseline, the Illumina HiSeq Platform was used to detect the methylation of 74 CpG sites of the P11 gene in peripheral blood samples. Resting-state functional magnetic resonance imaging (rs-fMRI) scan detected the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in 116 brain regions. The least absolute shrinkage and selection operator analysis method was used to perform feature reduction and feature selection. Four typical machine learning methods were used to establish support vector machine (SVM), random forest (RF), Naïve Bayes (NB), and logistic regression (LR) prediction models based on different combinations of functional activity of the brain, P11 gene DNA methylation and clinical/demographic features after screening. The SVM model based on ALFF, ReHo, FC, P11 methylation, and clinical/demographic features showed the best performance, with 95.92% predictive accuracy and 0.9967 area under the receiver operating characteristic curve, which was better than RF, NB, and LR models. The multidimensional data features combining rs-fMRI, DNA methylation, and clinical/demographic features can predict the early antidepressant efficacy in MDD.

T helper-1 activation via interleukin-16 is a key phenomenon in the acute phase of severe, first-episode major depressive disorder and suicidal behaviors

BackgroundImmune-inflammatory pathways in major depressive disorder are confined to the major dysmood disorder (MDMD) phenotype (Maes et al., 2022). No studies have addressed the immune profile of first episode MDMD (FE-MDMD). MethodsThis study investigated the immune profiles of 71 patients with the acute phase of first-episode major depressive disorder (FE-MDMD) and 40 healthy controls. We measured 48 cytokines/chemokines/growth factors, classical M1, alternative M2, T helper (Th)-1, Th-2, and Th-17 phenotypes, immune-inflammatory response system (IRS), compensatory immunoregulatory system (CIRS), and neuro-immunotoxicity profiles. ResultsFE-MDMD patients show significantly activated M1, M2, Th-1, IRS, CIRS, and neurotoxicity, but not Th-2 or Th-17, profiles compared to controls. FE-MDMD is accompanied by Th-1 polarization, while there are no changes in M1/M2 or IRS/CIRS ratios. The top single indicator of FE-MDMD was by far interleukin (IL)-16, followed at a distance by TRAIL, IL-2R, tumor necrosis factor (TNF)-β. The severity of depression and anxiety was strongly associated with IRS (positively) and Th-2 (inversely) profiles, whereas suicidal behavior was associated with M1 activation. Around 56–60% of the variance in depression, anxiety, and suicidal behavior scores was explained by IL-16, platelet-derived growth factor (PDGF) (both positively), and IL-1 receptor antagonist (inversely). Increased neurotoxicity is mainly driven by IL-16, TNF-α, TRAIL, IL-6, and chemokine (CCL2, CCL11, CXCL1, CXCL10) signaling. Antidepressant-treated patients show an increased IRS/CIRS ratio as compared with drug-naïve FE-MDMD patients. ConclusionsFE-MDMD is accompanied by positive regulation of the IRS mainly driven by Th-1 polarization and T cell activation (via binding of IL-16 to CD4), and TNF, chemokine, and growth factor signaling.

Cost-effectiveness analysis comparing repetitive transcranial magnetic stimulation therapy with antidepressant treatment in patients with treatment-resistant depression in Japan

Repetitive transcranial magnetic stimulation (rTMS) for patients with treatment-resistant depression (TRD) became covered by the National Health Insurance (NHI) in Japan since 2019. Although the evidence of rTMS for TRD is well established, the cost-effectiveness of rTMS versus antidepressants has not been thoroughly analyzed in Japan. Thus, we aimed to evaluate the cost-effectiveness of rTMS for TRD under the NHI system using a microsimulation model to compare the direct costs and quality-adjusted life years (QALYs). Model inputs of clinical parameters and the utility were derived from published literature. Cost parameters were estimated from the Japanese Claim Database. The robustness of the analyses was evaluated with sensitivity analysis and scenario analysis. The analysis estimated that rTMS increased effectiveness by 0.101QALYs and total cost by ¥94,370 ($689) compared with antidepressant medications. As a result, the incremental cost-effectiveness ratio (ICER) of rTMS was estimated to be ¥935,984 ($6,832)/QALY. In the sensitivity and scenario analyses, ICER did not exceed ¥5 million ($36,496)/QALY as the reference value of the Japanese public cost-effectiveness evaluation system. rTMS therapy for TRD can be a cost-effective treatment strategy compared to antidepressant medication under the NHI system in Japan.

Impact of antidepressant medication on the analgetic effect of repetitive transcranial magnetic stimulation treatment of neuropathic pain. Preliminary findings from a registry study.

Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective in chronic neuropathic pain conditions. However, information about the combined effects of rTMS and antidepressant treatment is scarce. We studied the outcome of rTMS and concurrent antidepressant treatment in patients with neuropathic pain. In this retrospective, real-world study, 34 patients with neuropathic pain, who were considered resistant or not benefitting from conventional treatment, received rTMS treatment between 2017 and 2020. Pain-related factors were measured using the Numerical Rating Scale (NRS), Global Impression of Change (GIC), and Beck Depression Inventory. A decrease in pain intensity and pain interference assessed with NRS was observed after 10 treatment sessions in 16 patients. The impression of change was positive in 20 patients. Half of the patients (n=17) used antidepressant medication, while half (n=17) did not. A concurrent use of antidepressants with therapeutic rTMS was significantly linked with less pain intensity relief when compared with the nonuse of antidepressants (p=0.019). The impression of change was significantly in favor of the antidepressant nonuser group (p=0.002). No group differences in pain interference were found between the groups. Therapeutic rTMS for neuropathic pain is plausibly sensitive to interference with antidepressant medication. The exact mechanism of our findings remains to be elucidated; confirmatory studies are warranted.

Design of a real-world, prospective, longitudinal, observational study to compare vortioxetine with other standard of care antidepressant treatments in patients with major depressive disorder: a PatientsLikeMe survey

BackgroundMajor depressive disorder (MDD) is a recurrent psychiatric condition that presents challenges in responding to treatment and achieving long-term remission. To improve outcomes, a shared decision-making treatment approach with patient and healthcare practitioner (HCP) engagement is vital. PatientsLikeMe (PLM), a peer community of patients, provides information on MDD, symptoms, and treatment through forums and resources, helping patients stay engaged in their treatment journey. Data on PLM can be harnessed to gain insights into patient perspectives on MDD symptom management, medication switches, and treatment goals and measures.MethodsThis ongoing, decentralized, longitudinal, observational, prospective study is being conducted using the PLM platform in two parts, enrolling up to 500 patients with MDD in the United States aged ≥ 18 years to compare vortioxetine with other monotherapy antidepressants. The first qualitative component consists of a webinar and discussion forum with PLM community members with MDD, followed by a pilot for functionality testing to improve the study flow and questions in the quantitative survey. The quantitative component follows on the PLM platform, utilizing patient-reported assessments, over a 24-week period. Three surveys will be conducted at baseline and weeks 12 and 24 to collect data on patient global impression of improvement, depression severity, cognitive function, quality of life (QoL) and well-being, medication satisfaction, emotional blunting, symptoms of anhedonia and resilience, as well as goal attainment. Quantitative results will be compared between groups. The qualitative component is complete; patient recruitment is underway for the quantitative component, with results expected in late 2023.DiscussionThese results will help HCPs understand patient perspectives on the effectiveness of vortioxetine versus other monotherapy antidepressants in alleviating symptoms of MDD and improvements in QoL. Data from the PLM platform will support a patient goal-based treatment approach, as results can be shared by patients with their HCPs, providing them with insights on patient-centric goals, treatment management and adherence, as well as allowing them to observe changes in patient-related outcomes scores. Findings from the study will also help to optimize the PLM platform to build scalable solutions and connectivity within the community to better serve patients with MDD.

Serotonergic Neurotransmission in Limbic Regions May Reflect Therapeutic Response of Depressive Patients: A PET Study With 11C-WAY-100635 and 18F-MPPF.

Central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission has been implicated in the etiology of depression. Most antidepressants ameliorate depressive symptoms by increasing 5-HT at synaptic clefts, but their effect on 5-HT receptors has yet to be clarified. 11C-WAY-100635 and 18F-MPPF are positron emission tomography (PET) radioligands for 5-HT1A receptors. While binding of both ligands reflects 5-HT1A receptor density, 18F-MPPF biding may also be affected by extracellular 5-HT concentrations. This dual-tracer PET study explored the neurochemical substrates underlying antidepressant effects in patients with depression. Eleven patients with depression, including 9 treated with antidepressants, and 16 age- and sex-matched healthy individuals underwent PET scans with 11C-WAY-100635 and 18F-MPPF. Radioligand binding was determined by calculating the nondisplaceable binding potential (BPND). Patients treated with antidepressants showed significantly lower 18F-MPPF BPND in neocortical regions and raphe nuclei, but not in limbic regions, than controls. No significant group differences in 11C-WAY-100635 BPND were found in any of the regions. Significant correlations of BPND between 11C-WAY-100635 and 18F-MPPF were observed in limbic regions and raphe nuclei of healthy controls, but no such associations were found in antidepressant-treated patients. Moreover, 18F-MPPF BPND in limbic regions was significantly correlated with the severity of depressive symptoms. These results suggest a diversity of antidepressant-induced extracellular 5-HT elevations in the limbic system among depressive patients, which is associated with the individual variability of clinical symptoms following the treatment.

Personal recovery associated with deep brain stimulation for treatment-resistant depression: A constructivist grounded theory study.

WHAT IS KNOWN ON THE SUBJECT?: Major depressive disorder is the most prevalent of all mental illnesses. 10%-20% of patients with depression and 1% of the population overall have treatment-resistant depression (TRD). DBS is an emerging investigational treatment for TRD with documented clinical efficacy and safety. The framework of the recovery model includes both clinical and personal recovery. Personal recovery is a self-process in which hope, empowerment and optimism are embraced to overcome the impact of mental illness on one's sense of self. Although clinical and functional outcomes of DBS for TRD have been well documented in the previous studies, personal recovery as an outcome has been explored only in a handful of studies. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first qualitative study exploring personal recovery from DBS treatment specific to the target of subcallosal cingulate cortex in patients with TRD. Since the existing literature on personal recovery in DBS studies is limited, the contribution of this paper is crucial to this field. For individuals who responded to deep brain stimulation clinically, neither participants nor family believed it cured their depression, but rather there was a significant decrease in the severity of symptoms of depression. A holistic-oriented framework (that includes personal recovery) is significant for those individuals with TRD undergoing DBS. Personal and clinical recovery are two different constructs, and individuals may experience one or the other or both. The experience of participants who responded to deep brain stimulation recognized that the recovery from depression is a process of reconstructing self. This process involved a period of adjustment that evoked a deeper self-awareness, re-engagement with daily living and newfound gratitude in living. Individuals transitioned from an emotionally driven life to one where future goals were considered. Supportive relationships were instrumental in this process. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: A deep brain stimulation intervention for treatment-resistant depression offered individuals an opportunity for personal recovery where a reconstruction of self occurred. Personal recovery can be considered as an outcome in conjunction with clinical and functional outcomes in future DBS trials for TRD. The relevance of personal recovery in the prevention of relapses needs further investigation. To advocate for care and services that facilitate the process of recovery from depression, it is important to understand the personal dimensions and experience of recovery that may influence the process. To develop recovery-oriented interventions to help patients and families in recovery post-deep brain stimulation, further understanding of support and negotiating relationships during this life-altering experience is needed. ABSTRACT: Introduction Multiple trials of antidepressant treatments in patients with depression pose a major challenge to the mental health system. Deep brain stimulation (DBS) is an emerging and promising investigational treatment to reduce depressive symptoms in individuals with treatment-resistant depression (TRD). The clinical and functional outcomes of DBS for TRD have been well documented in previous studies; however, studies of personal recovery as an outcome of DBS specific to the target of subcallosal cingulate cortex in patients with TRD are limited. Aim To explore the processes of personal recovery in patients with treatment-resistant depression following subcallosal cingulate-deep brain stimulation. Method Participants were 18 patients with TRD who participated in the subcallosal cingulate (SCC)-DBS trial and 11 family members. They also participated in add-on individual cognitive behavioural therapy during the trial. A qualitative constructivist grounded theory approach was used to conceptualize the personal recovery process of patients and families. Results While every participant and their families' journey were unique following the deep brain stimulation intervention, a theoretical model of Balancing to Establish a Reconstructed Self emerged from the data. The themes underlying the model were (1) Balancing to Establish a Reconstructed Self: A Whole-Body Experience, (2) The Liminal Space in-between: Balancing with Cautious Optimism, (3) Hope: Transitioning from Emotion-Focussed Living to Goal-Oriented Planning and (4) Support: Negotiating Relationships. Discussion This is the first study examining recovery from patients' perspectives as an outcome of SCC-DBS intervention for TRD. The study shows that personal recovery is a gradual and continual process of reconstruction of the self, developing through supportive relationships. Clinical and personal recovery are two distinct constructs, and individuals may experience one or the other or both. Most patients who do respond clinically experience improvement in terms of having optimism and hope. Some patients, however, respond with significant symptom reduction but are not able to achieve personal recovery to experience joy or hope for improved quality of living. Implications for Practice Strategies for personal recovery for both patients and family need to be considered during and post deep brain stimulation intervention. Nurses working with these patients and families may benefit from education, training and support to assess and engage in conversations about their recovery process.

Association between the loudness dependence of auditory evoked potential, serotonergic neurotransmission and treatment outcome in patients with depression

Previous studies have suggested that the loudness dependence of auditory evoked potential (LDAEP) is associated with the effectiveness of antidepressant treatment in patients with major depressive disorders (MDD). Furthermore, both LDAEP and the cerebral serotonin 4 receptor (5-HT4R) density is inversely related to brain serotonin levels.We included 84 patients with MDD and 22 healthy controls to examined the association between LDAEP and treatment response and its association with cerebral 5-HT4R density. Participants underwent both EEG and 5-HT4R neuroimaging with [11C]SB207145 PET. Thirty-nine patients with MDD were re-examined after 8 weeks of treatment with selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitor (SSRI/SNRI).We found that the cortical source of LDAEP was higher in untreated patients with MDD compared to healthy controls (p=0.03). Prior to SSRI/SNRI treatment, subsequent treatment responders had a negative association between LDAEP and depressive symptoms and a positive association between scalp LDAEP and symptom improvement at week 8. This was not found in source LDAEP. In healthy controls, we found a positive correlation between both scalp and source LDAEP and cerebral 5-HT4R binding but that was not observed in patients with MDD. We did not see any changes in scalp and source LDAEP in response to SSRI/SNRI treatment.These results support a theoretical framework where both LDAEP and cerebral 5-HT4R are indices of cerebral 5-HT levels in healthy individuals while this association seems to be disrupted in MDD. The combination of the two biomarkers may be useful for stratifying patients with MDD.Clinical Trials Registration:https://clinicaltrials.gov/ct2/show/NCT02869035?draw=1Registration number: NCT0286903.

Impact of Tai Chi as an adjunct treatment on brain connectivity in geriatric depression

BackgroundAs an adjunct to antidepressant treatment, Tai Chi Chih (TCC) is superior to health education and wellness (HEW) training in improving the general health of patients with geriatric depression (GD). This study investigated the brain connectivity changes associated with TCC and HEW in combination with antidepressant treatment in patients with GD. MethodsForty patients with GD under stable antidepressant treatment underwent TCC training (n = 21) or HEW training (n = 19) for 12 weeks, and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. Within-group and between-group differences in parcel-to-parcel connectivity changes with intervention were evaluated by general linear modeling. Relationships between significant connectivity changes and symptom/resilience improvement were evaluated by partial least squares correlation analysis. ResultsSignificantly greater increases in connectivity with TCC than with HEW (FDR-corrected p < .05) were observed for 167 pairwise connections, most frequently involving the default mode network (DMN). In both groups, increased connectivity involving largely DMN regions was significantly and positively correlated with improvement in symptoms/resilience. LimitationsThe sample size was relatively small, mainly due to neuroimaging contraindications (e.g., implants). Additionally, the standard antidepressant treatment varied greatly among patients, adding heterogeneity. ConclusionsNon-pharmacological adjuncts, such as TCC, may enhance DMN connectivity changes associated with improved depressive symptoms and psychological resilience in the treatment of GD.

Use of Clinical Global Impressions-Severity (CGI-S) to Assess Response to Antidepressant Treatment in Patients with Treatment-Resistant Depression.

BackgroundThis post-hoc analysis evaluated the agreement between Clinical Global Impressions-Severity (CGI-S) score- and Montgomery–Åsberg Depression Rating Scale (MADRS) total score-based assessment of response in patients with treatment-resistant depression (TRD) treated with esketamine nasal spray plus a newly initiated oral antidepressant (ESK-NS + AD).MethodsData were analyzed from a phase 3, randomized, double-blind study (TRANSFORM-2) of flexibly dosed esketamine or placebo nasal spray plus a newly initiated oral-AD in adults with moderate-to-severe TRD. Patients with ≥50% reduction in MADRS from baseline at the end of the 4-week acute treatment phase were defined as responders. For the CGI-S-based assessment of response, patients with ≥2 points decrease from baseline or a CGI-S score of ≤3 (mildly depressed to normal) were considered responders. Cohen’s kappa coefficient was calculated to assess level of agreement between MADRS and CGI-S-based assessments.ResultsAt the end of 4-week treatment, the proportion of responders among all study patients (n=201) was similar when assessed using the MADRS (61%) and CGI-S (62%) methods, with substantial agreement (Cohen’s kappa=0.76; sensitivity=92%; specificity=84%) between both methods. When restricting analysis to ESK-NS + AD-treated patients (n=101) who had a higher response rate (on MADRS: 69%; on CGI-S: 68%), the agreement remained substantial (Cohen’s kappa=0.75; sensitivity=91%; specificity=84%).ConclusionThe CGI-S may be a practical and reliable alternative to the MADRS to assess response to ESK-NS + AD in patients with TRD and can be used in real-world practice to support informed treatment decisions.

The association of C-reactive protein with responses to escitalopram antidepressant treatment in patients with major depressive disorder

BackgroundThe effects of escitalopram vary markedly among MDD patients, and approximately one-third of patients fail to respond. A poor antidepressant response might be associated with excessively high C-reactive protein (CRP) levels, but the impact is not clear. We hypothesized that in adults with major depressive disorder, the peripheral biomarker, CRP, was associated with the response to escitalopram (SSRI). MethodsThis was a prospective follow-up study. All 71 patients were treated with escitalopram for 12 weeks. Blood samples were collected at baseline and week 12. Remission was defined as a score of 7 or less on the HAMD-17 scale at week 12. Spearman correlations and multiple linear regressions were used to explore the relationship between continuous CRP levels and the HAMD-17 scores. Logistic regression was used to determine the predictors for remission. The restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) was used to examine the change of the HAMD-17 total scores between high and low CRP groups. ResultsCompared with the high CRP group (≥0.8 mg/l), the low baseline CRP group had a higher remission rate (22.73% vs. 48.89%, χ2 = 4.2, p = 0.0403). Logistic regression revealed that patients with lower CRPs were 3.920 times (95% CI: 1.142, 13.460) more likely to experience remission (p = 0.0300). The multiple linear regression model showed that the HAMD-17 total score reduction (baseline to week 12) was negatively correlated with the baseline CRP level (t = −2.00, p = 0.0494). ConclusionsWe observed a predictive role of CRP for remission and symptomatic improvement after escitalopram treatment of MDD patients based on continuous or categorical CRP levels.

Comparative change in P300 indices following antidepressant treatment in patients with major depressive disorder.

Cognitive disturbance is seen in patients with major depressive disorder (MDD). Event-related potential can assist in measuring the neurocognition, and P300 is the most commonly used noninvasive electrophysiological parameter for measuring cognition. The aim of this study is to assess the baseline P300 parameters, Hamilton Rating Scale for Depression (HAM-D), and Montgomery-Asberg Depression Rating Scale (MADRS) scores and compare them with their levels after 3 months of antidepressant therapy. a longitudinal study was done on total 24 diagnosed cases of major depression who underwent P300, HAM-D, and MADRS assessment in the gap of 3 months before and after starting antidepressant therapy. Newly diagnosed cases of MDD patients were assessed using HAM-D and MADRS for severity rating. P300 assessment was also carried out with auditory oddball paradigm using Nihon Kohden NCV-SMG-EP system. The assessments were repeated after 3 months of antidepressant treatment. The Wilcoxon test was used to compare mean values of P300 parameters, HAM-D, and MADRS score. Spearman correlation analysis was done to study the association between various parameters of P300 and HAM-D and MADRS score before and after treatment of 3 months of antidepressant therapy. Significant difference is shown in various parameters P300 except for A11-P300 amplitude and A31-P300 amplitude. A significant difference was shown in HAM-D and MADRS scores. No significant correlation was seen between other P300 parameters and HAM-D and MADRS scale before as well as after antidepressant therapy. P300 may be used as an index to evaluate the response to antidepressant treatment in patients with MDD.

Machine Learning and Deep Learning for the Pharmacogenomics of Antidepressant Treatments.

A growing body of evidence now proposes that machine learning and deep learning techniques can serve as a vital foundation for the pharmacogenomics of antidepressant treatments in patients with major depressive disorder (MDD). In this review, we focus on the latest developments for pharmacogenomics research using machine learning and deep learning approaches together with neuroimaging and multi-omics data. First, we review relevant pharmacogenomics studies that leverage numerous machine learning and deep learning techniques to determine treatment prediction and potential biomarkers for antidepressant treatments in MDD. In addition, we depict some neuroimaging pharmacogenomics studies that utilize various machine learning approaches to predict antidepressant treatment outcomes in MDD based on the integration of research on pharmacogenomics and neuroimaging. Moreover, we summarize the limitations in regard to the past pharmacogenomics studies of antidepressant treatments in MDD. Finally, we outline a discussion of challenges and directions for future research. In light of latest advancements in neuroimaging and multi-omics, various genomic variants and biomarkers associated with antidepressant treatments in MDD are being identified in pharmacogenomics research by employing machine learning and deep learning algorithms.

Prediction of residual cognitive disturbances by early response of depressive symptoms to antidepressant treatments in patients with major depressive disorder

BackgroundPatients with major depressive disorder (MDD) frequently retain cognitive disturbances after recovery from mood symptoms. We investigated the relationship between early response of mood symptoms and/or remission, and residual cognitive disturbances after 6 months of antidepressant treatment. Methods518 patients with MDD were followed up for 6 months after antidepressant treatment initiation (first-line or switch from a previous drug). Subjective and objective cognitive disturbances were assessed by the Perceived Deficits Questionnaire – Depression (PDQ-D) and digit symbol substitution test (DSST), respectively. Depressive symptoms, as well as remission and early response to treatment, were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Multivariable linear and logistic regression models were used to adjust for confounders. ResultsEarly response of depressive mood (≥50% reduction in MADRS score at month 1) was related with fewer residual subjective cognitive symptoms, as evaluated by the PDQ-D at month 6 (p<0.001). Likewise, early remission status at month 2 was inversely associated with PDQ-D scores at month 6 (p<0.001). Among patients with baseline DSST scores of ≥1 standard deviation below the norm, early response/remission was associated with better performance on the DSST at month 6 (p<0.05). LimitationsThe cohort may not be representative of the general MDD patient population, and the possible influence of concomitant medications was not evaluated. ConclusionsThese findings suggest that early improvements in depressive symptoms predict better cognitive outcomes in patients with MDD. Grouping of patients by mood and cognition status in early stages of antidepressant treatments may facilitate efforts to improve long-term functional outcomes.

Inflammatory cytokines, cognition, and response to antidepressant treatment in patients with major depressive disorder

BackgroundInflammation and cognition are related to major depressive disorder (MDD), but the role in treatment response remains unclear. In this study, we investigated correlation between inflammatory cytokines and cognition in MDD patients treated with antidepressant medication. MethodsThe participants were 149 MDD patients. Cytokines before therapy, cognitive assessments and severity of depression before and after therapy were tested. Logistic regression was used to explore underlying risks treatment response. ResultsThere were significant differences in smoking, alcohol drinking, and Stroop Color Test(SCT), Stroop Color-Word Test (SCWT), and Continuous Performance Test(CPT) scores between response group (RG) and non-response group (NRG) at baseline. Performance of patients in RG improved more in Brief Assessment of Cognition in Schizophrenia (BACS), Color Trial Test-I (CTT-I), SCT and SCWT after treatment. Levels of baseline IL-18 were associated with baseline learning and memory, and executive function. Treatment response was associated with drinking, performance of CPT and SCT. ConclusionMDD patients with different treatment responses have different cognitive defects, especially in speed of processing and executive function. Expression of cytokines is associated with cognition and may influence treatment response. Better speed of processing and executive function, and poorer attention at baseline may respond better to antidepressant treatment.

Randomized, Placebo-controlled, Antidepressant Treatment of Patients with Major Depressive Disorder: Changes in Glomerular Filtration Rate

BackgroundA bidirectional relationship between depression and renal dysfunction has been posited, however, a paucity of longitudinal data exists in individuals with major depression disorder (MDD). As depression may contribute to the progression of chronic kidney disease (CKD), we sought to determine whether effective depression treatment was associated with improvement in renal function. MethodsA retrospective analysis performed on 1600 outpatients who underwent double-blind, placebo-controlled, randomized antidepressant treatment (DBPCRAT) of MDD in thirteen Eli Lilly and Company clinical trials. Magnitude of depression symptoms was measured with the Hamilton Depression Rating scale (HAMD); glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. ResultsAfter 7 weeks of DBPCRAT, HAMD scores in the treatment group decreased by 11.8 points, compared to 9.3 points in the placebo group (p < 0.0001). In the antidepressant-treated group, eGFR decreased by 0.28 ml/min/1.73 m2 and by 0.88 ml/min/1.73 m2 in the placebo-treated group (p = 0.17). Predictors of HAMD score at week 7 were baseline HAMD score (B = 0.237; p < 0.001), and antidepressant treatment (B = −2.28, p < 0.001). Predictors of eGFR were baseline eGFR (B = 0.651, p < 0.0001), increasing age (B = −0.194, p < 0.0001), and female gender (B = −0.984, p = 0.013). ConclusionShort-term, MDD was not associated with clinically significant decrements in eGFR. Future studies will determine whether depression treatment over a more prolonged period of time is associated with improvement in eGFR, especially in minorities and other high-risk populations.