Antidepressants In Major Depressive Disorder Research Articles

Antidepressant exposure and long-term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder.

The use of antidepressants in major depressive disorder (MDD) has been reported to influence long-term risk of Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), but studies are conflicting. We used inverse probability weighted (IPW) Cox models with time-varying covariates in a retrospective cohort study among midlife veterans with MDD within the US Veterans Affairs healthcare system from January 1, 2000 to June 1, 2022. A total of 35,200 patients with MDD were identified. No associations were seen regarding the effect of being exposed to any antidepressant versus no exposure on AD/ADRD risk (events=1,056, hazard ratio=0.94, 95% confidence interval: 0.81 to 1.09) or the exposure to specific antidepressant classes versus no exposure. A risk reduction was observed for female patients in a stratified analysis; however, the number of cases was small. Our study suggests that antidepressant exposure has no effect on AD/ADRD risk. The association in female patients should be interpreted with caution and requires further attention. We studied whether antidepressant use was associated with future dementia risk. We specifically focused on patients after their first-ever diagnosis of depression. We used IPW Cox models with time-varying covariates and a large observation window. Our study did not identify an effect of antidepressant use on dementia risk. A risk reduction was observed in female patients, but the number of cases was small.

Alterations of the amplitude of low-frequency fluctuation induced by repetitive transcranial magnetic stimulation combined with antidepressants treatment for major depressive disorder

We investigated the neuroimaging changes and clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants in major depressive disorder (MDD) patients. We scanned 35 patients with MDD and 27 healthy controls (HC) with resting-state functional magnetic resonance imaging (fMRI) before and after treatment. We analyzed amplitude of low-frequency fluctuation (ALFF) and the correlation with clinical variables. The rate of significant efficacy after treatment was higher in the combination treatment group than in the antidepressant group, although not statistically significant. At baseline, ALFF increased in the left middle temporal, brain stem, and left cerebellum and decreased in the right anterior cingulate (ACC), right orbital frontal cortex (OFC), and right caudate. ALFF increased in the left fusiform and decreased in the right lingual gyrus, left middle occipital gyrus, and left superior occipital gyrus after antidepressants. ALFF increased in the right ACC, right OFC, and right rectus after combination treatment. ALFF changes in the right ACC/OFC were negatively correlated with HAMD changes. After treatment, abnormal activity in some brain regions normalized, but these regions differed between the two treatment groups. rTMS combined with antidepressants therapy may improve MDD symptoms by improving neuronal activity levels in the right ACC and right OFC.

Prediction of treatment response in major depressive disorder using a hybrid of convolutional recurrent deep neural networks and effective connectivity based on EEG signal.

In this study, we have developed a novel method based on deep learning and brain effective connectivity to classify responders and non-responders to selective serotonin reuptake inhibitors (SSRIs) antidepressants in major depressive disorder (MDD) patients prior to the treatment using EEG signal. The effective connectivity of 30 MDD patients was determined by analyzing their pretreatment EEG signals, which were then concatenated into delta, theta, alpha, and beta bands and transformed into images. Using these images, we then fine tuned a hybrid Convolutional Neural Network that is enhanced with bidirectional Long Short-Term Memory cells based on transfer learning. The Inception-v3, ResNet18, DenseNet121, and EfficientNet-B0 models are implemented as base models. Finally, the models are followed by BiLSTM and dense layers in order to classify responders and non-responders to SSRI treatment. Results showed that the EfficiencyNet-B0 has the highest accuracy of 98.33, followed by DensNet121, ResNet18 and Inception-v3. Therefore, a new method was proposed in this study that uses deep learning models to extract both spatial and temporal features automatically, which will improve classification results. The proposed method provides accurate identification of MDD patients who are responding, thereby reducing the cost of medical facilities and patient care.

White matter integrity and medication response to antidepressants in major depressive disorder: a review of the literature.

Major Depressive Disorder (MDD) is a severe psychiatric disorder characterized by selective impairments in mood regulation, cognition and behavior. Although it is well-known that antidepressants can effectively treat moderate to severe depression, the biochemical effects of these medications on white matter (WM) integrity are still unclear. Therefore, the aim of the study is to review the main scientific evidence on the differences in WM integrity in responders and non-responders to antidepressant medications. A record search was performed on three datasets (PubMed, Scopus and Web of Science) and ten records matched our inclusion criteria. Overall, the reviewed studies highlighted a good efficacy of antidepressants in MDD treatment. Furthermore, there were differences in WM integrity between responders and non-responders, mainly localized in cingulate cortices, hippocampus and corpus callosum, where the former group showed higher fractional anisotropy and lower axial diffusivity values. Modifications in WM integrity might be partially explained by branching and proliferation as well as neurogenesis of axonal fibers mediated by antidepressants, which in turn may have positively affected brain metabolism and increase the quantity of the serotonergic neurotransmitter within synaptic clefts. However, the reviewed studies suffer from some limitations, including the heterogeneity in treatment duration, antidepressant administration, medical posology, and psychiatric comorbidities. Therefore, future studies are needed to reduce confounding effects of antidepressant medications and to adopt longitudinal and multimodal approaches in order to better characterize the differences in WM integrity between responders and non-responders.

Placebo-controlled randomized clinical trials of antidepressants for major depressive disorder: Analysis of ClinicalTrials.gov, 2008–2022

The purpose of this study was to analyze the key aspects of the design of contemporary placebo-controlled randomized clinical trials (RCTs) of antidepressants enrolling patients with major depressive disorder (MDD) aged 18 years or older, especially the outcome measures and the eligibility criteria. The study included 122 RCTs registered with ClinicalTrials.gov and started from 2008 through 2022. Most RCTs assessed only clinical remission, with proportion of trials with outcome measures related to functional remission being rather low (n = 34; 28 %). Clinical remission was mostly evaluated in acute phase of depression, and only 7 (6 %) trials assessed the prevention of relapse. Proportion of trials utilizing self-report questionnaires that provide important information complementary to clinician-rated scales was moderate (n = 66; 54 %). Another problem in included RCTs was common use of stringent eligibility criteria. For instance, minimal symtpom severity required for the patient's inclusion was listed in 104 RCTs (85 %), and 41 RCTs (34 %) excluded patients based on comorbid anxiety disorders. Most RCTs (n = 103; 84 %) excluded older patients, and only 6 (5 %) trials were dedicated exclusively to them. To ensure optimal development of clinical pharmacotherapy of MDD, the investigators should consider modification of some of the key aspects of the design of RCTs of antidepressants.

Should probiotics be administered as an adjunctive treatment along with antidepressants for major depressive disorder?

Madam, Major depressive disorder (MDD) is a significant factor in global disability rates and contributes significantly to the overall disease burden worldwide. According to estimates, approximately 3.8% of the global population is impacted, with a prevalence of 5.0% among adults and 5.7% among adults aged 60 years and above [1]. It is also the leading cause of suicide among individuals. While the administration of antidepressants is the widely known and successful treatment for this mental disorder, recent research and accumulating evidence have demonstrated that probiotics also function effectively in controlling anxiety and depression. Probiotics that provide psychological benefits are now referred to as psychobiotics. Psychobiotics are defined as live organisms that, when consumed in sufficient quantities, produce unexpected health benefits in individuals with psychiatric disorders [2]. Around 30% of patients with major depressive disorder (MDD) do not respond to traditional antidepressant medications targeting monoamine pathways, indicating the involvement of other biological mechanisms in the development of MDD [3]. One particularly promising hypothesis regarding the pathogenesis of MDD is the dysfunction of the gut-brain axis (GBA), with the gut microbiota playing a crucial role [4]. Numerous studies have investigated the impact of probiotics on stress resilience. The recent meta-analysis discovered a significant finding: when probiotics were combined with antidepressants, they showed a remarkable reduction in depressive symptoms. However, when used alone, probiotics exhibited a less impact on alleviating depressive symptoms. This highlights the crucial role of combining probiotics with standard treatments for a more substantial effect on managing depression [5]. These impressive results elucidate the advantages of administering probiotic strains in individuals suffering from mental health disorders, specifically MDD, by effectively addressing the imbalance within the gut-brain axis (GBA) and suppressing stress-induced activation of biological pathways involved in psychological disturbances. Recurrent evidence has proven that gut microbiota play a significant role in neuronal homeostasis and any imbalance may contribute as a factor in the underlying mechanism of the pathogenesis of MDD. Henceforth, further research should be encouraged in order to develop promising microbiome-based therapeutics for MDD, and physicians should consider administering probiotics as an adjunctive treatment for depression alongside antidepressants. Moreover, the importance of probiotics should be thoroughly studied, and medical doctors should raise awareness of the significance of the gut-brain axis and associated biological pathways, which play a major role in an individual's mental health.

Multi-omics reveal microbial determinants impacting the treatment outcome of antidepressants in major depressive disorder

BackgroundThere is a growing body of evidence suggesting that disturbance of the gut-brain axis may be one of the potential causes of major depressive disorder (MDD). However, the effects of antidepressants on the gut microbiota, and the role of gut microbiota in influencing antidepressant efficacy are still not fully understood.ResultsTo address this knowledge gap, a multi-omics study was undertaken involving 110 MDD patients treated with escitalopram (ESC) for a period of 12 weeks. This study was conducted within a cohort and compared to a reference group of 166 healthy individuals. It was found that ESC ameliorated abnormal blood metabolism by upregulating MDD-depleted amino acids and downregulating MDD-enriched fatty acids. On the other hand, the use of ESC showed a relatively weak inhibitory effect on the gut microbiota, leading to a reduction in microbial richness and functions. Machine learning-based multi-omics integrative analysis revealed that gut microbiota contributed to the changes in plasma metabolites and was associated with several amino acids such as tryptophan and its gut microbiota-derived metabolite, indole-3-propionic acid (I3PA). Notably, a significant correlation was observed between the baseline microbial richness and clinical remission at week 12. Compared to non-remitters, individuals who achieved remission had a higher baseline microbial richness, a lower dysbiosis score, and a more complex and well-organized community structure and bacterial networks within their microbiota. These findings indicate a more resilient microbiota community in remitters. Furthermore, we also demonstrated that it was not the composition of the gut microbiota itself, but rather the presence of sporulation genes at baseline that could predict the likelihood of clinical remission following ESC treatment. The predictive model based on these genes revealed an area under the curve (AUC) performance metric of 0.71.ConclusionThis study provides valuable insights into the role of the gut microbiota in the mechanism of ESC treatment efficacy for patients with MDD. The findings represent a significant advancement in understanding the intricate relationship among antidepressants, gut microbiota, and the blood metabolome. Additionally, this study offers a microbiota-centered perspective that can potentially improve antidepressant efficacy in clinical practice. By shedding light on the interplay between these factors, this research contributes to our broader understanding of the complex mechanisms underlying the treatment of MDD and opens new avenues for optimizing therapeutic approaches.86QpdFZ1CFqqddzdYP5qf7Video

Esketamine vs Midazolam in Boosting the Efficacy of Oral Antidepressants for Major Depressive Disorder

Loss of a previously effective response while still using adequate antidepressant treatment occurs in a relatively high proportion of patients with major depressive disorder (MDD); therefore, there is a need to develop novel effective treatment strategies. To assess the efficacy and safety of a single subanesthetic dose of esketamine in boosting the efficacy of oral antidepressants for treating fluctuating antidepressant response in MDD. This single-center, double-blind, midazolam-controlled pilot randomized clinical trial was conducted at Beijing Anding Hospital, Capital Medical University in China. The study enrolled participants aged 18 years and older with fluctuating antidepressant response, defined as patients with MDD experiencing fluctuating symptoms after symptom relief and stabilization. Patient recruitment was conducted from August 2021 to January 2022, and participants were followed-up for 6 weeks. Data were analyzed as intention-to-treat from July to September 2022. All participants in the esketamine-treated group received intravenous esketamine at 0.2 mg/kg in 40 minutes. Participants in the midazolam control group received intravenous midazolam at 0.045 mg/kg in 40 minutes. The primary outcome was the response rate at 2 weeks, defined as a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included response rate at 6 weeks, remission rates at 2 and 6 weeks, and change in MADRS and Clinical Global Impression-Severity score from baseline to 6 weeks; remission was defined by a MADRS score of 10 or lower. A total of 30 patients (median [IQR] age, 28.0 [24.0-40.0] years; 17 [56.7%] female) were randomized, including 15 patients randomized to midazolam and 15 patients randomized to esketamine; 29 patients completed the study. Response rates at 2 weeks were significantly higher in the esketamine-treated group than in the midazolam control group (10 patients [66.7%] vs 1 patient [6.7%]; P < .001). Participants treated with esketamine experienced significantly greater reduction in MADRS score from baseline to 2 weeks compared with those treated with midazolam (mean [SD] reduction, 15.7 [1.5] vs 3.1 [1.3]; P < .001). No serious adverse events were observed in this trial, and no psychotogenic effects and clinically significant manic symptoms were reported. This pilot randomized clinical trial found that a single subanesthetic dose of esketamine could boost the efficacy of oral antidepressants in treating fluctuating antidepressant response, with a good safety profile. Chinese Clinical Trial Registry Identifier: ChiCTR2100050335.

Change of prescription for patients with schizophrenia or major depressive disorder during admission: real-world prescribing surveys from the effectiveness of guidelines for dissemination and education psychiatric treatment project

BackgroundPolypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge.MethodsData on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups.ResultsFor both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients.ConclusionsIt is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures.Trial registrationThe study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).

Pharmacogenetics to Personalize Dosing of Tricyclic Antidepressants in Major Depressive Disorder: A Randomized Clinical Trial (PITA study)

IntroductionTricyclic antidepressants (TCAs) have an important role in pharmacotherapy of Major Depressive Disorder (MDD). TCA dosing is aimed at achieving a concentration in the therapeutic window. Due to inter-individual differences in activity of Cytochrome P450 (CYP) 2D6 and 2C19, (enzymes involved in TCA metabolism) patients require an individualized dose. Currently, finding of a suitable dosage is a process of trial-and-error, including multiple drug concentration measurements and dose adjustments. A starting dose based on a patient CYP2D6 and CYP2C19 metabolizer phenotype may contribute to achieving a therapeutic concentration more quickly, possibly resulting in higher treatment efficacy and the occurrence of fewer adverse effects.ObjectivesWe aimed to study whether genotype-informed dosing in TCAs leads to faster attainment of therapeutic plasma concentrations, a higher reduction of depression severity symptoms and less adverse effects.MethodsWe conducted a double-blind randomized clinical trial, in which patients (18-65 years) diagnosed with severe MDD and eligible for treatment with a TCA were randomized in two treatment arms: The intervention arm (Pharmacogenetics Informed Treatment; PIT) and standard treatment (Treatment As Usual; TAU). Patients were treated with nortriptyline, clomipramine or imipramine for seven weeks and depressive symptom severity and adverse effects were monitored weekly. The primary outcome measure, time needed to attain a therapeutic drug concentration, was analyzed using Kaplan-Meier analyses. The secondary outcome measures, reduction in depressive symptoms and adverse effects, were analyzed with mixed model linear regression.ResultsIn total, we randomized 111 patients. The PIT group (n=56) reached a therapeutic plasma concentration significantly faster (Kaplan Meier, X2 (1) = 4.3, p=0.039) compared to TAU (n=55), especially for patients treated with nortriptyline. On average depressive symptoms decreased relatively more in PIT than in TAU, although this was not significantly different: F(6) = 0.45, p = 0.84. The severity of adverse events during the study period differed significantly between PIT and TAU (F(6)=3.10, p=0.008). PIT experienced fewer adverse effects than TAU, especially in the last two weeks of the study.ConclusionsGenotype-informed dosing leads to faster attainment of therapeutic TCA concentrations and does not lead to more adverse effects. Although we were not able to demonstrate that genotype-informed dosing leads to a significantly better response, we conclude that pharmacogenetics can contribute to the optimization of pharmacological treatment. Future research may focus on subgroups for which pharmacogenetics may be of great value, such as specific antidepressants or patients with an abnormal pharmacogenetic profile.Disclosure of InterestNone Declared

Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians.

Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants. English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research. 2 investigators independently selected randomized trials of at least 6 weeks' duration. Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest. 65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously. Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence. Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration. American College of Physicians. (PROSPERO: CRD42020204703).

Inflammation and Treatment-Resistant Depression from Clinical to Animal Study: A Possible Link?

The aim of this study was to investigate the relationship between treatment-resistant depression (TRD) and inflammation in humans and experimental models. For the human study, a retrospective cohort study was conducted with 206 participants; half were on antidepressants for major depressive disorder. The patients were divided into healthy and depressed groups. Inflammation was assessed based on the values of the main inflammatory biomarkers (CRP, WBC and ESR). For the animal experiments, 35 adult male Wistar rats were assigned to stressed and non-stressed groups. Inflammation and stress were induced using lipopolysaccharide and chronic unpredictable mild stress. A 10 mg/kg intraperitoneal injection of fluoxetine (FLX), a known antidepressant, was simultaneously administered daily for 4 weeks. Behavioral tests were performed. The plasma levels of inflammatory and stress biomarkers were measured and were significantly higher in the stressed and non-responsive groups in both studies. This study provides evidence of the link between inflammation and TRD. We further observed a possible link via the Phosphorylated Janus Kinase 2 and Phosphorylated Signal Transducer and Activator of Transcription 3 (P-JAK2/P-STAT3) signaling pathway and found that chronic stress and high inflammation hinder the antidepressant effects of FLX. Thus, non-response to antidepressants could be mitigated by treating inflammation to improve the antidepressant effect in patients with TRD.

Effect of Concomitant Benzodiazepines on the Antidepressant Effects of Ketamine

Objective: Ketamine is a novel and rapidly acting treatment for major depressive disorder (MDD). Benzodiazepines are commonly coprescribed with antidepressants in MDD. This study sought to examine data from a randomized clinical trial that compared a single infusion of intravenous (IV) ketamine to midazolam placebo in treatment-resistant depression (DSM-IV-TR MDD) and to assess whether the use of concomitant oral benzodiazepines differentially affected treatment response to ketamine versus midazolam. Methods: This trial ran from December 2015 to December 2016. Subjects who were taking oral benzodiazepines (n = 44) were compared to those who were not (n = 55). A significant treatment-by-benzodiazepine effect could be interpreted as a possible moderator of differential treatment response to ketamine versus midazolam. Benzodiazepine use was examined as both a binary and a continuous predictor, to assess the impact of dosage. Results: Benzodiazepine users did not differ from non-users on the original study’s primary outcome measure, score on the 6-item Hamilton Depression Rating Scale (HDRS-6), at baseline, but the former had more severe anxiety. When oral benzodiazepine use was modeled as a binary predictor, benzodiazepine use did not impact differential treatment response. However, when benzodiazepine dosage was considered, there was a significant impact of benzodiazepine use on differential treatment response. Oral benzodiazepines significantly impacted HDRS-6 (P = .018) and Clinical Global Impressions–Severity of Illness scale (CGI-S; P = .008) scores at day 1 (24 hours post treatment); effects were nonsignificant for all day 3 outcomes. Among ketamine subjects, higher doses of benzodiazepines were associated with less improvement in depression scores at day 1. Conclusions: Concomitant oral benzodiazepines at higher doses may attenuate the antidepressant effects of IV ketamine at day 1 but not day 3 post-infusion. Trial Registration: ClinicalTrials.gov identifier: NCT01920555.

Association between the Rostral Anterior Cingulate Cortex and Anterior Insula in the Salience Network on Response to Antidepressants in Major Depressive Disorder as Revealed by Isolated Effective Coherence

Introduction: Functional connectivity is attracting increasing attention for understanding the pathophysiology of depression and predicting the therapeutic efficacy of antidepressants. In this study, we evaluated effective connectivity using isolated effective coherence (iCoh), an effective functional connectivity analysis method developed from low-resolution brain electromagnetic tomography (LORETA) and estimated its practical usefulness for predicting the reaction to antidepressants in theta and alpha band iCoh values. Methods: We enrolled 25 participants from a depression treatment randomized study (the GUNDAM study) in which electroencephalography was performed before treatment. We conducted iCoh between the rostral anterior cingulate cortex (rACC) and anterior insula (AI), which are associated with the salience network. The patients were divided into responder and nonresponder groups at 4 weeks after the start of treatment, and iCoh values were compared between the two groups. Additionally, the sensitivity and specificity of iCoh were calculated using the receiver-operating characteristic (ROC) curve. Results: The Mann-Whitney U test showed significantly weaker connectivity flow from the rACC to the left AI in the alpha band in the responder group. The ROC curve for the connectivity flow from the rACC to the left AI in the alpha band showed 82% sensitivity and 86% specificity. Discussion/Conclusion: These findings suggest the pathological importance of effective connectivity flow from the rACC to the left AI in the alpha and theta bands and suggest its usefulness as a biomarker to distinguish responders to antidepressants.

Cortical thickness and related depressive symptoms in early abstinence from chronic methamphetamine use.

Methamphetamine use is surging globally as a cause of morbidity and mortality. Treatment is typically sought in early abstinence, when craving and depressive symptoms are intense, contributing to relapse and poor outcomes. To advance an understanding of this problem and identify therapeutic targets, we conducted a retrospective analysis of brain structure in 89 adults with Methamphetamine Use Disorder who were in early abstinence and 89 healthy controls. Unlike most prior research, the participants did not significantly differ in age, sex and recent use of alcohol and tobacco (p-values ≥ 0.400). We analysed thickness across the entire cerebral cortex by fitting a general linear model to identify differences between groups. Follow-up regressions were performed to determine whether cortical thickness in regions showing group differences was related to craving, measured on a visual analogue scale, or to the Beck Depression Inventory score. Participants in early methamphetamine abstinence (M ± SD = 22.1 ± 25.6 days) exhibited thinner cortex in clusters within bilateral frontal, parietal, temporal, insular, and right cingulate cortices relative to controls (p-values < 0.001, corrected for multiple comparisons). Unlike craving (β =0.007, p= 0.947), depressive symptoms were positively correlated with cortical thickness across clusters (β =0.239, p = 0.030) and with thickness in the anterior cingulate cluster (β =0.246, p = 0.027) in the methamphetamine-dependent group. Inasmuch as anterior cingulate pathology predicts response to antidepressants for Major Depressive Disorder, cingulate structure may also identify patients with Methamphetamine Use Disorder who can benefit from antidepressant medication.

Vortioxetine Modulates the Regional Signal in First-Episode Drug-Free Major Depressive Disorder at Rest.

BackgroundPrevious studies on brain functional alterations associated with antidepressants for major depressive disorder (MDD) have produced conflicting results because they involved short treatment periods and a variety of compounds.MethodsResting-state functional magnetic resonance imaging scans were obtained from 25 first-episode drug-free patients with MDD and 25 healthy controls. The patients, who were treated with vortioxetine for 8 weeks, were scanned at two-time points (baseline and week 8 of treatment). The amplitude of low-frequency fluctuation (ALFF) in the imaging data was used to analyze local brain signal alterations associated with antidepressant treatment.ResultsCompared with the controls, the patients at baseline showed decreased ALFF values in the right inferior temporal gyrus and increased ALFF values in the left inferior cerebellum, right cingulate gyrus and postcentral gyrus. After 8 weeks of vortioxetine treatment, patients showed increased ALFF values in the bilateral cingulate gyrus, middle temporal gyrus, medial superior frontal gyrus, and inferior cerebellum.ConclusionThis study provided evidence that vortioxetine modulates brain signals in MDD sufferers. These findings contribute to the understanding of how antidepressants effect brain function.

Clinical Phenotypes Characterization in Pharmacogenetics Testing Trials for Major Depressive Disorder Treatment

Several data indicate that the success of pharmacological treatment in major depressive disorder (MDD) is still unsatisfactory. The determination of the optimal treatment generally requires multiple trials with different treatments, with the sobering observation that the more treatments tried without success, the less likely a successful outcome, with the result of a long unremitted disease, worse long term prognosis, increased rates of side effects, and important medical, social and economic burden. The reasons for the low response and remission rates are multiple and depend on environmental and biological factors intrinsic to the disease and drug treatments. Pharmacogenetic (PG) tests have the potential to increase efficacy predicting outcome and to reduce antidepressant discontinuation due to side effects. Several studies investigated the utility of PG tests for antidepressants in MDD with interesting but contrasting results. To date most of them are observational studies with no comparator group, and few are randomized controlled trials (RCTs). Several limitations concerning study design, generalization of results, duration of trials, patients group studied, and cost-effectiveness ratio were found, and a number of barriers have been noted in the adoption of PG tests into clinical practice. Despite some preliminary positive results, there is the need for larger and longer‐term RCT studies, with the goal to capture the real impact of PG tests, also with stratified analysis concerning MDD features in terms of severity and antidepressant treatment failures in different ethnicity cohorts.DisclosureNo significant relationships.

Evaluating study designs and treatment outcomes of antidepressant pharmacogenetic clinical trials - Challenges and future perspectives. A critical review

Several data indicate that the success of pharmacological treatment in major depressive disorder (MDD) is still unsatisfactory. The reasons for the low response and remission rates are multiple and depend on environmental and biological factors intrinsic to the disease and drug treatments. Pharmacogenetic (PG) tests have the potential to increase efficacy predicting outcome and to reduce antidepressant discontinuation due to side effects. Several studies investigated the utility of PG tests for antidepressants in MDD with interesting but contrasting results. To date most of them are observational studies with no comparator group, and few are randomized controlled trials (RCTs). The aim of this review is to provide an evaluation of the state of art on clinical methodologic features of RCTs with PG tests for antidepressant drugs in MDD, offering suggestions and favoring new insights that could be useful in the implementation of future trials. Several limitations concerning study design, generalization of results, duration of trials, patients group studied, and cost-effectiveness ratio were found, and a number of barriers have been noted in the adoption of PG tests into clinical practice. Despite some preliminary positive results, there is the need for larger and longer‐term RCT studies, with the goal to capture the real impact of PG tests, also with stratified analysis concerning MDD features in terms of severity and antidepressant treatment failures in different ethnicity cohorts.

Baseline patterns of resting functional connectivity within posterior default-mode intranetwork associated with remission to antidepressants in major depressive disorder

BackgroundThe default mode network (DMN) is implicated in the pathophysiology of major depressive disorder (MDD), and functional connectivity (FC) involved in DMN is suggested to be associated with antidepressant remission. The goal of this study is to recognize relationships between FC within DMN and early amelioration in MDD patients and to further test the capacity of FC to predict early efficacy. MethodsIn total 66 MDD patients and 57 healthy controls were recruited for resting-state functional magnetic resonance imaging scans at baseline. After four weeks of treatment with Escitalopram or Venlafaxine, patients were divided into subgroups with remitters (R, n = 31) and non-remitters (NR, n = 35). Independent component analysis (ICA) was used to compare intranetwork functional connectivity (intra-FC) in DMN between the three groups. ResultsRelative to NR-MDD group and HCs, the R-MDD group showed significantly higher intra-FC in the right angular gyrus of DMN, and the intra-FC was positively correlated with the reduction ratio of the depressive symptom scores. The ROC curve analysis revealed that intra-FC exhibited a high diagnostic value for remission. ConclusionThese findings indicated that intra-FC related to the DMN is a prognostic marker that can potentially predict early remission of symptoms after antidepressant treatment.

Baseline Patterns of Resting Functional Connectivity within Posterior Default-Mode Intranetwork Associated with Remission to Antidepressants in Major Depressive Disorder

Baseline Patterns of Resting Functional Connectivity within Posterior Default-Mode Intranetwork Associated with Remission to Antidepressants in Major Depressive Disorder