Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial.

Following on from our pilot studies, this study aimed to test the efficacy of a combination of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus), magnesium orotate and coenzyme 10 for the treatment of major depressive disorder (MDD) through a double-blind placebo controlled clinical trial. The participants were 120 adults diagnosed with MDD randomised to daily oral administration, over 8 weeks, of either the intervention or placebo, with a 16-week follow-up period. Intent-to-treat analysis found a significantly lower frequency of the presence of a major depressive episode in the intervention group compared with placebo at the end of the 8-week treatment phase, with no difference between the two conditions at 8-week follow-up. Both the categorical and continuous measure of depressive symptoms showed a significant difference between the two conditions at 4 weeks, but not 8 and 16 weeks. The secondary end-point was demonstrated with an overall reduction in self-rated symptoms of anxiety and stress in the active treatment group compared with placebo. These findings suggest that the combination of probiotics, magnesium orotate and coenzyme 10 may be an effective treatment of MDD over an 8-week period.

Clinical experience with parenteral trazodone in mood disorders: A literature review. / Doswiadczenia kliniczne z trazodonem stosowanym droga pozajelitowa w zaburzeniach nastroju: przeglad literatury.

Trazodone is a serotonin antagonist/reuptake inhibitor, approved for treating major depressive disorder (MDD). Oral formulations are widely studied and marketed in several countries worldwide while there is little evidence to support use of parenteral formulation. Our narrative review summarizes pharmacological properties and clinical data concerning use of parenteral trazodone in mood disorders. PubMed and Web of Science were used to identify the most relevant literature. The main evidence concerns four studies evaluating efficacy in major depressive disorder and indicates that trazodone was well tolerated and effective. Off-label use in agitation associated with bipolar disorder is also reported in three studies, although prescription of concomitant treatment, as a confounding factor, may have influenced outcome measures. The limited available evidence supports parenteral trazodone use in major depressive disorder and suggests that trazodone is a suitable option in patients at high risk of treatment-emergent mania (TEM).

The Effects of Selective Serotonin Reuptake Inhibitors on Impulsivity in Young Adults with Major Depression in the Early Phase of Treatment. / Majör Depresyonu Olan Genç Eriskinlerde Selektif Serotonin Geri Alim Inhibitörlerinin Tedavinin Erken Döneminde Dürtüsellik Üzerine Etkisi.

OBJECTIVE: Whether selective serotonin reuptake inhibitors (SSRI) increase suicide risk, especially in young adults, is still a controversial issue. This study aimed to examine the change in impulsivity characteristics and to evaluate the relationship between impulsivity and suicidality in young adults with major depression who were started on SSRIs. METHOD: The study included 50 patients between the ages of 18-24 years with a diagnosis of major depression who were planned to start SSRIs. Participants were evaluated with the Beck Depression Scale, Beck Anxiety Scale, Young Mania Rating Scale, Columbia Suicide Severity Rating Scale, Barratt Impulsivity Scale, Daily Impulsivity Scale (DIS), and Go/ No-Go Task (GNG) before and at the end of the first week of treatment. RESULTS: Seventy percent of the patients (n: 35) completed the assessments at baseline and at the end of the first week. At the end of one-week there was a statistically significant decrease in the DIS (t=2.283, p=0.029) and commission errors in GNG (t=3.19, p=0.003). In addition, 7 out of 11 patients who had suicidal ideation at the first evaluation did not continue to have suicidal ideation at the end of the first week and there was a significant decrease in the severity of suicidal ideation at the end of the follow-up (W:132.0, p<0.001). CONCLUSION: One-week SSRI use in young adults resulted in a decrease in impulsivity in self-report scales assessing state impulsivity and in the GNG. It was observed that the severity of suicidal ideation decreased at the end of the one-week treatment period.

Self-stigmatization and treatment preferences: Measuring the impact of treatment labels on choices for depression medications.

OBJECTIVE: To collect evidence on the possibility that patients with depression experience self-stigmatization based on label information for medications. METHODS: We developed a discrete-choice experiment (DCE) survey instrument that asked respondents to make choices between hypothetical treatments for major depressive disorder (MDD). We also included treatment type (antidepressants versus antipsychotics) and approved indications for the medication. The choice questions mimicked the information presented in product inserts and required systematic tradeoffs between treatment efficacy, treatment type, and indication. We calculated how many patients were willing to forgo efficacy to avoid treatments with information associated with self-stigmatization, and how much efficacy they were willing to forgo. We also evaluated the impact of contextualizing the treatment information to reduce self-stigmatization by randomizing respondents who received additional context. RESULTS: A total of 501 patients with MDD were recruited to complete the DCE survey. Respondents had well-defined preferences for treatment outcomes. Over 60% (63.4%) of respondents were found to be significantly affected by treatment indication. These respondents were willing to forgo about 2.5 percentage points in the chance of treatment efficacy to avoid treatments indicated for schizophrenia. We also find that some level of contextualization of the treatment details could help reduce the negative impact of treatment type and indications. CONCLUSIONS: Product-label treatment indication can potentially lead to patient self-stigmatization as shown by patients' avoidance of treatments that are also used to treat schizophrenia. While the effect appears to be relatively small, results suggests that the issue is likely pervasive.

Baseline Cognition Is Not Associated With Depression Outcomes in Vortioxetine for Major Depressive Disorder: Findings From Placebo-Controlled Trials.

Objective: Major depressive disorder (MDD) is a common psychiatric disorder for which pharmacologic standard-of-care treatments have limited efficacy, particularly among individuals with cognitive dysfunction. Cognitive dysfunction is observed in approximately 25%-50% of those with MDD, wherein response to standard-of-care medications is reduced. Vortioxetine is an approved antidepressant that has shown evidence of procognitive effects in patients. It is not known if it has greater clinical efficacy in MDD patients with cognitive dysfunction, a more difficult to treat population, than other antidepressants.Methods: This study was a reanalysis of 1,812 subjects with MDD across 4 placebo controlled trials. Baseline cognition was measured by the Digit Symbol Substitution Test (DSST), the primary measure used to demonstrate vortioxetine's procognitive effects in clinical studies. Analyses examined whether baseline cognitive function was associated with differences in treatment outcomes.Results: Baseline DSST did not predict placebo-adjusted treatment effects of vortioxetine on depressive symptoms (pooled Cohen d = -0.02, 95% CI = -0.12 to 0.07). Analyses of additional cognitive measures similarly did not predict placebo-adjusted treatment effects on depression (all 95% CI contained zero). Finally, analyses of trials with selective serotonin reuptake inhibitors (SSRIs)/serotonin and norepinephrine reuptake inhibitors (SNRIs) as active comparators also revealed no prediction of SSRI/SNRI adjusted treatment effects of vortioxetine on depression.Conclusions: These findings, taken together, suggest that cognitive function does not moderate depression outcomes in vortioxetine, with results comparable to other antidepressants.

Pre- and Post-Synaptic protein in the major depressive Disorder: From neurobiology to therapeutic targets.

Major depressive disorder (MDD) has demonstrated its negative impact on various aspects of the lives of those affected. Although several therapies have been developed over the years, it remains a challenge for mental health professionals. Thus, understanding the pathophysiology of MDD is necessary to improve existing treatment options or seek new therapeutic alternatives. Clinical and preclinical studies in animal models of depression have shown the involvement of synaptic plasticity in both the development of MDD and the response to available drugs. However, synaptic plasticity involves a cascade of events, including the action of presynaptic proteins such as synaptophysin and synapsins and postsynaptic proteins such as postsynaptic density-95 (PSD-95). Additionally, several factors can negatively impact the process of spinogenesis/neurogenesis, which are related to many outcomes, including MDD. Thus, this narrative review aims to deepen the understanding of the involvement of synaptic formations and their components in the pathophysiology and treatment of MDD.

Unveiling the interoception impairment in various major depressive disorder stages.

BACKGROUND: The intricate pathophysiological mechanisms of major depressive disorder (MDD) necessitate the development of comprehensive early indicators that reflect the complex interplay of emotional, physical, and cognitive factors. Despite its potential to fulfill these criteria, interoception remains underexplored in MDD. This study aimed to evaluate the potential of interoception in transforming MDD's clinical practices by examining interoception deficits across various MDD stages and analyzing their complex associations with the spectrum of depressive symptoms. METHODS: This study included 431 healthy individuals, 206 subclinical depression individuals, and 483 MDD patients. Depressive symptoms and interoception function were assessed using the PHQ-9 and MAIA-2, respectively. RESULTS: Interoception dysfunction occurred in the preclinical phase of MDD and further impaired in the clinical stage. Antidepressant therapies showed limited efficacy in improving interoception and might damage some dimensions. Interoceptive dimensions might predict depressive symptoms, primarily enhancing negative thinking patterns. The predictive model based on interoception was built with random split verification and demonstrated good discrimination and predictive performance in identifying MDD. CONCLUSIONS: Early alterations in the preclinical stage, multivariate associations with depressive symptoms, and good discrimination and predictive performance highlight the importance of interoception in MDD management, pointing to a paradigm shift in diagnostic and therapeutic approaches.

Relative value of novel systemic immune-inflammatory indices and classical hematological parameters in predicting depression, suicide attempts and treatment response.

This study compared the power of the novel inflammatory markers systemic immune inflammation index (SII) and the system inflammation response index (SIRI) versus the classical hematological indices neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and platelet counts in distinguishing between major depressive disorder (MDD) with and without suicide attempts and distinguishing the non-response to selective serotonin reuptake inhibitor (SSRI) treatment. A total of 139 young adult MDD patients and 54 healthy controls (HC) were included. We found that, in comparison to HC, baseline NLR, PLR, SII, and SIRI were significantly higher in MDD patients, but only NLR and SII had area under the ROC curve (AUC) values greater than 0.7. MDD patients with suicide attempts (SA) showed significantly higher baseline MLR and SIRI, and a tendency to increase NLR compared to those without SA. In terms of AUC, sensitivity, and specificity, NLR was better than MLR, SIRI, SII, and PLR in distinguishing SA. Non-responders to SSRI treatment showed a significant increase in baseline platelet count and PLR compared to responders with an AUC greater than 0.7. These findings highlight the potential benefit of combining novel and classical hematological indices in predicting depression, suicide attempts and treatment response.

ElectroRetinoGraphy toward an exploration of the therapeutic potential of antidepressants in patients with major depressive disorder: A scoping review of the literature.

Major Depressive Disorder (MDD) is characterized by at least one major depressive episode. It requires medical attention typically involving the prescription of antidepressants. Remission in MDD patients is often difficult to achieve because of the limited effectiveness of these drugs. Nowadays, numerous patients undergo various antidepressant treatments, with subjective changes in their personal experiences being regularly monitored. Therefore, it is essential to find clinical and objective tools that offer a more tailored approach to antidepressant selection. The neurochemistry of the retina being similar to the brain, one promising approach would be to use ElectroRetinoGraphy (ERG) measurements on MDD patients requiring antidepressant treatment. Thus, the aim of this scoping review is to highlight effects of different classes of antidepressants on retinal function evaluated by full-field ERG (ffERG), Pattern ERG (PERG) and multifocal ERG (mfERG) waveforms in MDD patients. These ERG measurements could serve as pivotal indicators in defining patient profiles, facilitating a more objective and personalized approach to therapeutic interventions, thereby advancing precision psychiatry.

Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression.

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

The Antidepressant Action of Fluoxetine Involves the Inhibition of Dlx5/6 in Cortical GABAergic Neurons through a TrkB-Dependent Pathway.

Major depressive disorder (MDD) is a complex and devastating illness that affects people of all ages. Despite the large use of antidepressants in current medical practice, neither their mechanisms of action nor the aetiology of MDD are completely understood. Experimental evidence supports the involvement of Parvalbumin-positive GABAergic neurons (PV-neurons) in the pathogenesis of MDD. DLX5 and DLX6 (DLX5/6) encode two homeodomain transcription factors involved in cortical GABAergic differentiation and function. In the mouse, the level of expression of these genes is correlated with the cortical density of PV-neurons and with anxiety-like behaviours. The same genomic region generates the lncRNA DLX6-AS1, which, in humans, participates in the GABAergic regulatory module downregulated in schizophrenia and ASD. Here, we show that the expression levels of Dlx5/6 in the adult mouse brain are correlated with the immobility time in the forced swim test, which is used to measure depressive-like behaviours. We show that the administration of the antidepressant fluoxetine (Flx) to normal mice induces, within 24 h, a rapid and stable reduction in Dlx5, Dlx6 and Dlx6-AS1 expression in the cerebral cortex through the activation of the TrkB-CREB pathway. Experimental Dlx5 overexpression counteracts the antidepressant effects induced by Flx treatment. Our findings show that one of the short-term effects of Flx administration is the reduction in Dlx5/6 expression in GABAergic neurons, which, in turn, has direct consequences on PV expression and on behavioural profiles. Variants in the DLX5/6 regulatory network could be implicated in the predisposition to depression and in the variability of patients' response to antidepressant treatment.

Predicting treatment response to ketamine in treatment-resistant depression using auditory mismatch negativity: Study protocol.

BACKGROUND: Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear. OBJECTIVE: This study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions. METHODS: This is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes. CONCLUSION: The findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information. TRIAL REGISTRATION: Clinicaltrials.gov NCT05464264. Registered June 24, 2022.

Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis.

QUESTION: Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder. STUDY SELECTION AND ANALYSIS: We conducted a systematic review with meta-analysis and trial sequential analysis. We searched CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to January 2023 for randomised clinical trials comparing tricyclic antidepressants versus placebo or 'active placebo' for adults with major depressive disorder. The primary outcomes were depressive symptoms measured on the 17-item Hamilton Depression Rating Scale (HDRS-17), serious adverse events and quality of life. The minimal important difference was defined as three points on the HDRS-17. FINDINGS: We included 103 trials randomising 10 590 participants. All results were at high risk of bias, and the certainty of the evidence was very low or low. All trials only assessed outcomes at the end of the treatment period at a maximum of 12 weeks after randomisation. Meta-analysis and trial sequential analysis showed evidence of a beneficial effect of tricyclic antidepressants compared with placebo (mean difference -3.77 HDRS-17 points; 95% CI -5.91 to -1.63; 17 trials). Meta-analysis showed evidence of a harmful effect of tricyclic antidepressants compared with placebo on serious adverse events (OR 2.78; 95% CI 2.18 to 3.55; 35 trials), but the required information size was not reached. Only 2 out of 103 trials reported on quality of life and t-tests showed no evidence of a difference. CONCLUSIONS: The long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events, but these results were based on low and very low certainty evidence. PROSPERO REGISTRATION NUMBER: CRD42021226161.

LSDDEP2: study protocol for a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged as a self-treatment approach for depression within lay communities. Building upon preliminary evidence and the successful completion of an open-label pilot trial of microdosing LSD for depression (LSDDEP1), this protocol outlines a phase 2b randomised controlled trial (LSDDEP2). The main objective of LSDDEP2 is to assess the modification of depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), following a regimen of LSD microdoses versus placebo. METHODS: This is a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients meeting DSM-5 criteria for major depressive disorder. Participants will undergo an 8-week LSD microdosing regimen using the titratable MB-22001 formulation taking two doses a week. All doses will be self-administered at home and will be titratable from 4 to 20 µg based on subjective perception and tolerability. In addition to depression symptoms, outcome will include psychiatric and personality inventories, sleep and activity tracking, electroencephalography (EEG), blood biomarkers, semi-structured interviews, and safety (e.g. adverse event, laboratory exam) measures. DISCUSSION: This study will be the first randomised controlled trial to administer controlled microdoses of LSD for treatment of MDD in participants' naturalistic environment. The measures included are designed to assess the drug's safety, mechanism, and treatment efficacy over placebo in this population. The results of this study will be important for assessing the viability of psychedelic microdosing as an additional treatment option and for informing the direction of future clinical trials. TRIAL REGISTRATION: ANZCTR, ACTRN12624000128594. Prospectively Registered on 13 February 2024.

Analysis of Medication Adherence Status and Influencing Factors in Adolescents with Major Depressive Episodes.

BACKGROUND: By analyzing the current status and influencing factors of medication adherence in adolescent patients with major depressive episode, this study aimed to provide more evidence on clinical medication treatment of such patients. METHODS: This was a retrospective study. A total of 218 adolescents with major depressive disorder (MDD) admitted to the mental health center of the First Affiliated Hospital of Guangxi Medical University from June 2022 to June 2023 were selected as the study subjects. The 8-item Morisky Medication Adherence Questionnaire (MAQ-8) was used to group the patients. All of the patients were collected in accordance with general sociological characteristics and disease characteristics. Conducted χ2 test, t-test, and binary logistic regression analysis. p values less than 0.05 indicated statistically significant differences. RESULTS: A total of 218 adolescents with MDD were included in this study. The average score of MAQ-8 was 4.44 ± 2.09, of which 139 (63.76%) with a score less than 6 were included in the medication non-adherence group. Six to eight points with 79 cases (36.24%) were included in the medication compliance group. Family economic status (odds ratio (OR) = 6.211, 95% confidence interval (CI) 2.761-13.974), family history (OR = 2.298, 95% CI 1.043-5.062), course of diseases (OR = 2.107, 95% CI 1.002-4.429), Beck Depression Inventory (BDI) score (OR = 2.303, 95% CI 1.043-5.084), drug side effects (OR = 7.139, 95% CI 3.257-15.647), attitude to treatment (OR = 2.583, 95% CI 1.221-5.466), and satisfaction with doctors (OR = 2.338, 95% CI 1.08-5.064) were the effect of medication adherence. CONCLUSION: Severe depression of adolescent patients with poor medication compliance, as well as influencing factors, including family economic conditions, family history, course of diseases, BDI score, and drug side effects, were clinically investigated to formulate corresponding measures and improve patients' medication adherence.

Psychotropic Medications Promote Time-Dependent Reduction of Suicidal Ideation in Mood Disorder: A Prospective Cohort Study.

BACKGROUND: Despite a plethora of research on the topic, there is still no solid evidence that pharmacological treatment actually reduces the risk of suicide in patients with mental illness. In this study, we aimed to assess the effect of psychotropic medications on suicidal ideation in patients with major depressive disorder (MDD) and bipolar disorder (BPD) in two age groups: less than 25 years and 25 years and older. METHODS: We analyzed 312 patients with mood disorders with current suicidal thoughts or recent suicide attempts. We followed the participants from baseline for 6 months and assessed changes in suicidal ideation with Columbia-Suicide Severity Rating Scale (C-SSRS). The effect of psychotropic drug administration on suicidal ideation over time was analyzed using a linear mixed model. RESULTS: In patients aged 25 years and older with mood disorders, suicidal ideation was more severe when using psychotropic drugs than when not using them. However, suicidal ideation decreased rapidly over time. The time-dependent reduction in suicidal ideation was accelerated when using antidepressants and sedatives/hypnotics in adult MDD, and when using mood stabilizers in adult BPD. However, this effect was not observed in participants aged less than 25 years. CONCLUSION: Adequate psychotropic medication may reduce suicidal ideation in patients with mood disorders aged 25 years and older. Additional research on psychotropic drugs is needed to effectively reduce the risk of suicide among children and adolescents with mood disorders.

Safety and effectiveness of vortioxetine in patients with major depressive disorder in a real-life clinical setting in India: results from an interventional, flexible-dose study.

OBJECTIVE: Vortioxetine has demonstrated safety and efficacy in improving symptoms of major depressive disorder (MDD), including overall functioning in real-world settings. This is the first study in a real-life clinical setting in India to evaluate effectiveness and safety of vortioxetine in patients with MDD. METHODS: This interventional, open-label study consisted of a 12-week treatment period with flexible doses of vortioxetine (5-20 mg/day) in adult patients (aged 18-65 years) with a confirmed MDD diagnosis. Effectiveness outcomes included change from baseline to week 12 in Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression-Severity (CGI-S) scores, along with CGI-Improvement (CGI-I) scores at week 12, using a mixed model for repeated measures. Adverse events (AEs) were recorded for safety outcome assessments. RESULTS: Of 395 patients who received vortioxetine, 42.3% were women mean age 38.9 years; 322 patients completed the study. Significant improvement in depressive symptoms was observed in change from baseline to week 12 least squares (LS) mean (SE) PHQ-9 total score (-9.36 [0.276]; p<.0001) and CGI-S score (-2.14 [0.065]; p<.0001). LS mean (SE) CGI-I score showed significant improvement at week 12 (1.93 [0.067]; p<.0001). Subgroup analysis across age, sex, disease severity, and body mass index showed significant improvements in depression symptoms and severity. A total of 35.4% (n = 140) of patients experienced treatment-emergent AEs (mostly mild-moderate); nausea and pruritus were the most frequent (6.6%, n = 26 each). CONCLUSION: Safety and effectiveness of vortioxetine in improving symptoms of MDD over a 12-week period was demonstrated in a real-life clinical setting in India. CLINICAL TRIAL REGISTRATION INFORMATION: Open-label, flexible-dose study of vortioxetine in patients with major depressive disorder in India; Clinical Trials.gov ID: NCT04288895; https://www.clinicaltrials.gov/study/NCT04288895.

The dose-response relationship of vortioxetine on major depressive disorder: an umbrella review.

Vortioxetine is a novel multimodal antidepressant, but its precise efficacy and dose-response relationship for treating different symptoms in major depressive disorder (MDD) is still unclear. This umbrella review aims to assess the effectiveness, tolerability, and dose-response relationship of vortioxetine across a comprehensive range of clinical features in adults with MDD, including cognition, depression, anxiety, quality of life, and side effects. We meticulously searched eight electronic databases and included systematic reviews (SRs) and meta-analyses (MAs) of vortioxetine. The methodological quality of each included SR was independently assessed using the AMSTAR2 tool. To evaluate the credibility of the evidence, we utilized the GRADE framework and the Ioannidis criteria. In total, 35 SRs with 278 MAs met the inclusion criteria and based on these studies we performed 56 MAs of interest. While vortioxetine has been consistently shown to have positive effects on various domains, the evidence regarding cognitive performance and depression symptoms is notably robust compared to placebo, despite of relatively overall low quality of evidence. Finally, a dose-response relationship was observed across all categories within the treatment range of 5-20 mg/d and a dosage of vortioxetine 20 mg/d is recommended for adult MDD patients to achieve full functional recovery.