This study evaluated adverse events (AEs) associated with Vortioxetine by analyzing extensive data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We collected data from the FAERS database spanning ten years, from the first quarter of 2014 to the second quarter of 2024, focusing on drug-related AEs involving Vortioxetine. A comprehensive analysis was performed using multiple signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Among 13,116 reports where Vortioxetine was identified as the primary suspect drug, AEs were categorized into 27 system organ classes (SOCs) and 146 preferred terms (PTs). The results highlighted significant signals for common AEs, such as psychiatric disorders, gastrointestinal disorders, and nervous system disorders. Notably, feeling guilty exhibited the strongest signal strength; however, its clinical relevance requires cautious interpretation. Additionally, the study identified novel signals not listed in the drug label but potentially of clinical value, such as hyperarousal and alcoholic, which were significantly associated with Vortioxetine. Of particular note, AEs related to sexual dysfunction were the most diverse, while suicidal ideation was the most frequently reported. The study also uncovered rare but noteworthy signals, including hallucination and olfactory disorders, dermatillomania, and bruxism, which warrant further attention. In conclusion, while Vortioxetine demonstrates multifaceted benefits in alleviating symptoms of depression, its clinical use requires a comprehensive evaluation of potential risks. Developing safe and rational treatment strategies is essential to optimize therapeutic outcomes.

This narrative review used manufacturer-sponsored vortioxetine clinical trial database (doses of 5-20 mg) to evaluate the effect of vortioxetine treatment on short- and long- term functional outcomes in major depressive disorder (MDD), in both the clinical trial setting and in routine practice. The Sheehan Disability Scale (SDS) was the most used functional scale and, based on this measure, short-term, placebo-controlled studies demonstrated significant improvements with vortioxetine 10 mg (reductions ranged from -0.92 to -2.10 points vs placebo after 6-8 weeks treatment) and 20 mg (reductions ranged from -0.88 to -3.92 vs placebo). Of note, the acute beneficial effects of vortioxetine on functionality were seen in patients with severe baseline depressive symptoms as well as those with significant anxiety. Long-term open-label extension studies further showed that maintenance treatment was associated with continued functional improvements over one year (reaching an average reduction of -6.2 SDS points from baseline) that were correlated with continued improvements in residual symptoms. Evidence from real-world studies, using multiple functional outcomes, further demonstrated generalizability to routine practice where patients are living with multiple comorbidities previously excluded from the randomized controlled trials. Taken overall, the findings from several head-to-head studies indicated a functional advantage of vortioxetine compared with other classes of antidepressants and demonstrated the effectiveness of vortioxetine as first-line treatment while also confirming its effectiveness in improving functional outcomes when given later in the treatment journey. In summary, vortioxetine is an effective treatment option for improving functional outcomes in people living with MDD.

Background/Objectives: Major depressive disorder (MDD) is a major global health concern that is intimately linked to neuroinflammation, oxidative stress, mitochondrial dysfunction, and complicated metabolic abnormalities. Traditional antidepressants frequently fall short, highlighting the urgent need for new, safer, and more acceptable therapeutic techniques. Phytochemicals, i.e., natural antidepressants derived from plants, are emerging as powerful plant-based therapies capable of targeting many pathogenic pathways at the same time. Summary: This narrative review synthesizes evidence from preclinical and clinical studies on the efficacy of phytochemicals such as curcumin, polyphenols, flavonoids, and alkaloids in lowering depressed symptoms. Consistent data show that these substances have neuroprotective, anti-inflammatory, and antioxidant properties, altering neuroimmune interactions, reducing oxidative damage, and improving mitochondrial resilience. Particularly, polyphenols and flavonoids have great therapeutic potential because of their capacity to penetrate the blood-brain barrier, inhibit cytokine activity, and encourage neuroplasticity mediated by brain-derived neurotrophic factor (BDNF). Despite promising results, the heterogeneity in study designs, phytochemical formulations, and patient demographics highlights the importance of thorough, standardized clinical studies. Conclusions: This review identifies phytochemicals as compelling adjuvant or independent therapies in depression treatment, providing multimodal mechanisms and enhanced tolerability. Additional research into improved dosage, pharmacokinetics, long-term safety, and integrative therapy approaches is essential. Using phytotherapeutics could considerably improve holistic and customized depression care, encouraging new research routes in integrative neuroscience and clinical psychiatry.

The 5-HT1A receptor is expressed widely across the brain and is implicated in the mechanism of action of several therapeutics for mood disorders. However, there is limited and contradictory evidence about the role of this receptor in emotional processing and cognition.

The current study tested the acute effects of a single dose of the 5-HT1A agonist buspirone (20 mg), on a range of emotional processing (Emotional Test Battery) and cognitive (Auditory Verbal Learning Task (AVLT) and N-back) tasks in healthy, male and female volunteers (N = 62). The study was a randomised, double-blind, placebo controlled, parallel group design.

Buspirone reduced accuracy for detection of facial expressions of disgust and increased misclassification of negative facial emotions. It had no significant effects on categorisation or recall of emotionally-valanced words. Buspirone also reduced recall accuracy in the AVLT but had no significant effect in the N-back task. Participants receiving buspirone were more likely to experience nausea, light-headedness and sleepiness.

Acute buspirone administration produced a mild impairment in verbal memory and a subtle negative bias in emotional processing in healthy volunteers. These effects are consistent with the mixed effects of buspirone on pre- and post-synaptic 5-HT1A receptors.

Cognitive impairments following post-stroke significantly hinder neurological recovery and exacerbate patient morbidity, underscoring urgent need for effective therapeutic strategies. Vortioxetine (VTX), a prominent Selective Serotonin Reuptake Inhibitor (SSRI), boasts notable antidepressant, cognition-enhancing, and anti-inflammatory properties. This investigation delves into VTX's influence on motor skills, spatial learning-memory capabilities, and depressive behaviors in Middle Cerebral Artery Occlusion (MCAO) rats, alongside its underlying mechanisms. Our findings reveal that while VTX fails to entirely reverse ischemic-reperfusion damage, it substantially ameliorates spontaneous locomotor functions, augments post-stroke learning-memory capacities, and exhibits potent antidepressant and anxiety-like efficacy. Preliminary data propose that these beneficial effects may stem from inflammation modulation via the Toll-Like Receptor 2 (TLR-2)/Nuclear Factor-Kappa B (NF-κB) signaling pathway. Collectively, our work underscores VTX's promising role in enhancing motor, cognitive functions, and mitigating depressive symptoms following cerebrovascular accidents, potentially through inflammation regulation. These insights pave the way for novel interventions addressing post-stroke complications, warranting further exploration.

Interpatient variability in bipolar I depression (BP-D) symptoms challenges the ability to predict pharmacotherapeutic outcomes. A machine learning workflow was developed to predict remission after 8 weeks of pharmacotherapy (total score of ≤8 on the Montgomery Åsberg Depression Rating Scale [MADRS]).

Supervised machine learning models were trained on data from BP-D patients treated with olanzapine (N = 168) and were externally validated on patients treated with olanzapine/fluoxetine combination (OFC; N = 131) and lamotrigine (LTG; N = 126). Top predictors were used to develop a prognosis rule informing how many symptoms should change and by how much within 4 weeks to increase the odds of achieving remission.

An AUC of 0.76 (NIR:0.59; p = 0.17) was established to predict remission in olanzapine-treated subjects. These trained models achieved AUCs of 0.70 with OFC (NIR:0.52; p < 0.03) and 0.73 with LTG (NIR:0.52; p < 0.003), demonstrating external replication of prediction performance. Week-4 changes in four MADRS symptoms (reported sadness, reduced sleep, reduced appetite, and concentration difficulties) were top predictors of remission. Across all pharmacotherapies, three or more of these symptoms needed to improve by ≥2 points at Week-4 to have a 65% chance of achieving remission at 8 weeks (OR: 3.74, 95% CI: 2.45-5.76; p < 9.3E-11).

Machine learning strategies achieved cross-trial and cross-drug replication in predicting remission after 8 weeks of pharmacotherapy for BP-D. Interpretable prognoses rules required only a limited number of depressive symptoms, providing a promising foundation for developing simple quantitative decision aids that may, in the future, serve as companions to clinical judgment at the point of care.

Early research on the pharmacotherapy for major depressive disorder (MDD) has largely focused on symptomatic improvements, whereas this focus has shifted to functioning and quality of life in recent years. Studies have confirmed that antidepressants generally improve the functional outcomes in MDD, but very few works have compared the efficacies of specific drugs. The present work aims to compare the impacts of trazodone once-a-day extended-release (XR) vs selective serotonin reuptake inhibitors (SSRIs) on the health status and quality of life in MDD.

Data were gathered from 180 subjects through a naturalistic observation study of trazodone effectiveness in depression (TED) and analyzed. The TED study participants received trazodone XR of SSRIs in flexible doses for 12 weeks. The health status and health-related quality of life (HRQoL) were evaluated using the EQ-5D-5L tool at baseline as well as 2, 4, 8, and 12 weeks.

At baseline, the subjects treated with trazodone XR vs SSRIs presented similar health status profiles and HRQoL values with respect to the mobility, self-care, and anxiety/depression dimensions along with lower scores for the usual activities, pain/discomfort, overall HRQoL, and health status. Both trazodone XR and SSRIs improved the health status and HRQoL of the MDD patients at all subsequent timepoints. Compared to SSRIs, trazodone XR provided greater improvements in terms of the self-care, usual activities, pain/discomfort, and anxiety/depression measures and more often improved participant overall health status and HRQoL. More participants reported mixed changes in their health status and HRQoL in the SSRI group than the trazodone XR group.

Health status and HRQoL improved in both treatment arms, with preferable scores in trazodone XR vs. SSRIs group.

In multiple sclerosis (MS), alongside the physical symptoms, individuals often grapple with anxiety and depressive symptoms as prevalent comorbidity. Mood disturbances, frequently undertreated in clinical practice, significantly impact the quality of life of individuals with MS, exacerbating disability and hindering overall well-being. Furthermore, traditional antidepressant therapies are often associated with adverse events, such as sexual side effect, weight gain, which could limit their use in these patients. Vortioxetine is one of the most innovative antidepressant drugs in the current pharmacopeia. Its pharmacological profile includes serotonin reuptake inhibition, antagonism for hydroxytryptamine (HT) receptors 5-HT3, 5-HT1D and 5-HT7, partial agonism for 5-HT1B, and agonism for 5-HT1A. It has been shown to have a beneficial effect on depression-related cognitive dysfunction, as well as on anxiety, depression, anhedonia and emotional blunting. Recently a potential anti-inflammatory action was also described. Limited clinical studies have specifically explored the efficacy of vortioxetine in treating depressive symptoms in MS. However, extrapolating from existing research in major depressive disorder, it is plausible that vortioxetine's multimodal mechanism could provide a favorable therapeutic approach. This position paper, which summarizes the output of annual clinical meeting held by the DMSTs in MS Italian Study Group, is focused on the possible role that vortioxetine could play as symptomatic treatment (ST) of depressed patients with MS, hypothesizing a direct impact on the clinical course of the disease.

The frequent co-occurrence of major depressive disorder (MDD) and substance use disorders (SUDs) entails significant clinical challenges. Compared to patients with MDD alone, patients with MDD and SUD often show increased anhedonia, emotional blunting, and impaired cognitive function. These symptoms lead to an inability to control cravings, more substance use, increased relapse rates, and poor adherence to the treatment. This fosters a detrimental cycle leading to more severe depressive symptoms, functional impairment, and chronicity, culminating in heightened morbidity, mortality, and healthcare resource utilization. Data on antidepressant treatment of MDD-SUD patients are inconclusive and often conflicting because of a number of confounding factors in clinical trials or difficulty in dissecting the specific contributions of pharmacological versus psychological interventions in real-world studies. The patient's unique clinical features and specific SUD and MDD subtypes must be considered when choosing treatments. Ideally, drug treatment for MDD-SUD should act on both conditions and address core symptoms such as anhedonia, craving, and cognitive dysfunction while ensuring minimal emotional blunting, absence of drug interactions, and no addictive potential. This approach aims to address unmet needs and optimize the outcomes in a clinical population often underrepresented in treatment paradigms.

Cinnamon oil, an essential oil extracted from plants of the genus Cinnamomum, has been highly valued in ancient Chinese texts for its medicinal properties. This review summarizes the chemical composition, pharmacological actions, and various applications of cinnamon oil, highlighting its potential in medical and industrial fields. By systematically searching and evaluating studies from major scientific databases including Web of Science, PubMed, and ScienceDirect, we provide a comprehensive analysis of the therapeutic potential of cinnamon oil. Research indicates that cinnamon oil possesses a wide range of pharmacological activities, covering antibacterial, anti-inflammatory, anti-tumor, and hypoglycemic effects. It is currently an active ingredient in over 500 patented medicines. Cinnamon oil has demonstrated significant inhibitory effects against various pathogens comprising Staphylococcus aureus, Salmonella, and Escherichia coli. Its mechanisms of action include disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, suggesting its potential as a natural antimicrobial agent. Its anti-inflammatory properties are evidenced by its ability to suppress inflammatory markers like vascular cell adhesion molecules and macrophage colony-stimulating factors. Moreover, cinnamon oil has shown positive effects in lowering blood pressure and improving metabolism in diabetic patients by enhancing glucose uptake and increasing insulin sensitivity. The main active components of cinnamon oil include cinnamaldehyde, cinnamic acid, and eugenol, which play key roles in its pharmacological effects. Recently, the applications of cinnamon oil in industrial fields, including food preservation, cosmetics, and fragrances, have also become increasingly widespread. Despite the extensive research supporting its medicinal value, more clinical trials are needed to determine the optimal dosage, administration routes, and possible side effects of cinnamon oil. Additionally, exploring the interactions between cinnamon oil and other drugs, as well as its safety in different populations, is crucial. Considering the current increase in antibiotic resistance and the demand for sustainable and effective medical treatments, this review emphasizes the necessity for further research into the mechanisms and safety of cinnamon oil to confirm its feasibility as a basis for new drug development. In summary, as a versatile natural product, cinnamon oil holds broad application prospects and is expected to play a greater role in future medical research and clinical practice.

Treatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with other oral antidepressants.

To assess the efficacy of Vortioxetine plus ESK-NS in mitigating depressive symptoms and emotional blunting, as well as its tolerability in TRD subjects, compared to the standard-of-care of SSRI/SNRI plus ESK-NS.

We conducted a post-hoc analysis of the REAL-ESK study. The study included twenty TRD patients, ten subjects taking Vortioxetine as the main oral antidepressant with ESK-NS, and ten subjects taking SSRI or SNRI with ESK-NS. Psychometric assessments (Montgomery-Åsberg Depression Rating Scale/MADRS, Brief Psychiatric Rating Scale/BPRS) were conducted at baseline(T0), one month(T1), and three months after the treatment initiation(T2).

The combination of Vortioxetine and ESK-NS was as effective as the standard-of-care in reducing depressive symptoms, with a higher effect size in reducing emotional blunting at T2. The safety and tolerability profile of the Vortioxetine+ESK-NS combination appeared to be better, with a lower rate of treatment-emergent adverse events.

The combination of Vortioxetine and ESK-NS may be a valuable alternative to the standard-of-care SSRI/SNRI plus ESK-NS in TRD patients, particularly regarding the reduction of emotional blunting and potentially a better safety and tolerability profile. Further randomized controlled trials with larger sample sizes and prospective designs are needed to confirm these findings.

In VIVRE (NCT04448431), vortioxetine was associated with significantly higher rates of symptomatic and functional remission, better daily and social functioning, and greater treatment satisfaction than desvenlafaxine in patients with major depressive disorder (MDD) and partial response to selective serotonin reuptake inhibitor (SSRI) therapy. This analysis further explored the relative improvement in patient functioning with vortioxetine versus desvenlafaxine.

VIVRE was a randomized, double-blind study of vortioxetine (10 or 20 mg/day) versus desvenlafaxine (50 mg/day) in adults with MDD and partial response to initial SSRI monotherapy. Mean percentage changes from baseline to week 8 in Functioning Assessment Short Test (FAST) total and domain scores were analyzed by treatment group in the overall population and in working patients.

In the overall population, the mean reduction in FAST total score from baseline after 8 weeks of treatment was 37.2% in vortioxetine-treated patients versus 31.8% in desvenlafaxine-treated patients (P = 0.04). Significantly greater improvements versus desvenlafaxine were seen in vortioxetine-treated patients for FAST autonomy, cognitive functioning, and interpersonal-relationships scores (all P < 0.05). In working patients, the mean reduction in FAST total score from baseline at week 8 was 38.7% versus 32.1% in the vortioxetine and desvenlafaxine groups, respectively (P = 0.04). Significant correlations were seen between absolute changes in patient functioning, and those in depression severity and health-related quality of life.

Vortioxetine was significantly better than desvenlafaxine in improving overall functioning as well as daily, social, and cognitive functioning in patients with MDD with inadequate response to prior SSRI therapy.

Anhedonia constitutes a core symptom of major depressive disorder (MDD) mediating the ultimate goal of MDD treatment: functional remission. Anhedonia is also present in other clinical populations, including patients with chronic pain. Recent data links anhedonia to insulin resistance (IR). Some researchers have underlined a different dimension of anhedonia as a temperament/personality trait. The objective of this post-hoc analysis was to explore the links between anhedonia (main outcome) and (1) IR, (2) temperamental, personality, and schizotypy traits (exposures). The study population included patients with MDD, fibromyalgia, and healthy controls. Participants were split into groups: (1) insulin resistant (IR[+] n = 69, HOMA-IR ≥ 2.1) and (2) insulin sensitive (IR[-] n = 69, HOMA-IR < 2.1). Anhedonia was significantly higher in the IR[+] group than the IR[-] group. IR was a predictor of higher anhedonia levels. IR[+] vs. IR[-] participants showed higher levels of anxiety and lower levels of hyperthymic affective temperaments, as well as conscientiousness and emotional stability personality traits. Depressive, irritable, and anxious temperaments, cognitive disorganization, and introvertive anhedonia positively predicted anhedonia, while hyperthymic temperament, conscientiousness, extraversion, and emotional stability traits negatively predicted anhedonia. IR partially mediated the relationship between depressive temperament and anhedonia. In sum, IR, affective temperaments, and personality traits are predictors of anhedonia.

The multinational, open-label COMPLETE study (NCT03835715) investigated the effectiveness of vortioxetine in alleviating emotional blunting in patients with major depressive disorder (MDD) experiencing inadequate response and emotional blunting while being treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI). This paper presents results for the subgroup of patients enrolled in Spain.

Patients with MDD (n = 67) experiencing partial response and emotional blunting during monotherapy with an SSRI or SNRI were switched to vortioxetine (10-20 mg/day) for 8 weeks. The primary study outcome was emotional blunting, assessed by the Oxford Depression Questionnaire (ODQ).

After 8 weeks of vortioxetine, the mean (SE) change in ODQ total score from baseline was -26.0 (2.9) (P < 0.001). Respective changes in Montgomery-Åsberg Depression Rating Scale (MADRS), Motivation and Energy Inventory, Digit Symbol Substitution Test, and Sheehan Disability Scale (SDS) total scores were -14.9 (0.8), +34.2 (4.5), +6.3 (1.6), and ‒9.0 (1.3) (all P < 0.001 vs baseline). At week 8, 70.4% of patients no longer reported emotional blunting and 53.7% had achieved remission from their depressive symptoms (defined as a MADRS total score ≤10). Mediation analysis showed 77.1% of the change in SDS total score to be a direct effect of the improvement in ODQ total score after switching to vortioxetine. Adverse events were reported by 35 patients (52.2%), most commonly nausea (14 patients, 20.9%). At week 8, 33/54 patients (61.1%) were receiving vortioxetine 20 mg/day.

In this study investigating the effectiveness of vortioxetine in Spanish patients with MDD who experienced inadequate response and emotional blunting on SSRI/SNRI monotherapy, significant improvements in emotional blunting, core depressive symptoms (including anhedonia), sleep duration, motivation and energy, cognitive performance, and overall patient functioning were observed during the 8 weeks of treatment. Two-thirds of patients no longer reported emotional blunting and over half were in remission from their depressive symptoms at week 8.

Depression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression.

A systematic search of electronic databases was conducted using the search terms "baicalin" AND "depression" OR "depressed" OR "anti-depression". Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools.

Baicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = -39.3, 95%CI (-49.71, -28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = -39.73, 95%CI (-48.77, -30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001].

Baicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181.

Chronic pain (CP) and depression/anxiety often coexist, worsening each other's symptoms. Treating this comorbidity is challenging. Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are the first-line treatment options for this comorbidity, although sometimes they are not effective and/or well tolerated by patients, and there is little clinical evidence that selective serotonin reuptake inhibitors are useful for controlling CP. The antidepressant vortioxetine, with a multimodal mechanism that may help reduce pain, has proven clinical efficacy in patients with major depressive disorder (MDD). This study investigated vortioxetine's effectiveness for MDD and CP in clinical practice.

This was a 3-month, multicenter, prospective, open-label, non-interventional pharmacoepidemiologic study. Patients (n = 64) with MDD (9-item Patient Health Questionnaire [PHQ-9] score ≥ 15) and CP (visual analogue scale [VAS] score ≥ 4) were treated with vortioxetine for 3 months (initiated with 10 mg/day, with flexible dosing thereafter [5-20 mg/day]). VAS, Clinical Global Impression (CGI), and Patient Global Impression (PGI) scales were used at baseline and at 1 and 3 months. Brief Pain Inventory (BPI), PHQ-9 scale, and Satisfaction with Medicines Questionnaire (SATMED-Q) were used at baseline and at 3 months. Adverse Events (AEs) were recorded. Descriptive statistics, chi-square tests, and Student's t-tests were used for paired data.

MDD patients showed a statistically significant improvement in VAS from baseline (mean [standard deviation (SD)]: 7.42 [0.69]) to 1 month (mean [SD]: 6.1 [0.81], P < 0.001) and 3 months (mean [SD]: 5.09 [1.26], P < 0.0001). Similarly, BPI and PHQ-9 scores showed significant improvement from baseline (mean [SD]: 6.20 [0.80] and 16.63 [1.47], respectively) to 3 months (mean [SD]: 4.73 [0.98] and 7.30 [2.60], P < 0.0001, respectively). Patients showed clinical improvement with CGI and PGI scales and reported being satisfied with the treatment in the SATMED-Q. A few mild EAs were registered.

Vortioxetine can relieve depressive and pain symptoms, with a good safety profile, in patients with MDD and CP.

Depression is a highly heterogeneous disorder, often resulting in suboptimal response and remission rates. This underscores the need for more nuanced clinical characterization of patients to tailor individualized treatment plans. Emerging evidence highlights the critical role of cognitive and emotional dysfunction in major depression, prompting the exploration of novel therapeutic interventions that target these specific symptom domains.

Vortioxetine, a multimodal antidepressant, enhances serotonergic activity while also modulating several other neurotransmitter systems involved in depressive symptoms such as emotional blunting, anhedonia, and cognitive dysfunction. Numerous randomized, placebo-controlled trials have demonstrated vortioxetine's efficacy and safety in treating depression, particularly in specific subgroups of depressed patients, including those with cognitive deficits and comorbid anxiety symptoms or disorders. Although not randomized or placebo-controlled, studies have also shown vortioxetine's efficacy in depressed patients with emotional blunting or anhedonia. Vortioxetine's ability to effectively treat a range of depressive symptoms, including anhedonia, emotional blunting, anxiety, and cognitive dysfunction, provides an individualized treatment solution for depressed individuals suffering from these symptoms. The purpose of this paper is to identify clinical profiles of patients who may benefit from vortioxetine, with the goal of optimizing therapeutic outcomes.

Vortioxetine has been shown to be effective for patients with depression and symptoms such as anhedonia, emotional blunting, anxiety, and cognitive dysfunction. Tailoring treatment plans to individual needs and personalizing treatment choices based on the specific symptoms presented by depressed patients improve treatment outcomes.

Major Depressive Disorder (MDD) is a mental health issue that significantly affects patients' quality of life and functioning. Despite available treatments, many patients continue to suffer due to incomplete symptom resolution and side effects.

This manuscript examines Vortioxetine's role in Major Depressive Disorder (MDD) treatment, highlighting its potential to reshape therapeutic strategies due to its unique Multimodal action and proven broad-spectrum efficacy in multiple depressive domains. A detailed examination of Vortioxetine's pharmacological aspects, including indications, dosage, pharmacodynamics, and pharmacokinetics, is provided, emphasizing its safety and effectiveness. The discussion extends to Vortioxetine's role in acute-phase treatment and maintenance of MDD and its profound impact on specialized depression domains.

Vortioxetine is distinguished for its novel multimodal serotonin modulation mechanism, showcasing significant promise as an innovative treatment for MDD. Its efficacy, which is dose-dependent, along with a commendable tolerability profile, positions it as a potential leading option for initial treatment strategies. The discourse on dosage titration, particularly the strategy of initiating treatment at lower doses followed by gradual escalation, underscores the approach toward minimizing initial adverse effects while optimizing therapeutic outcomes, aligning with the principles of personalized medicine in psychiatric care.

Vortioxetine has been shown to improve cognitive performance in people with depression. This study will look at the changes in neurobiochemical metabolites that occur when vortioxetine improves cognitive performance in MDD patients, with the goal of determining the neuroimaging mechanism through which vortioxetine improves cognitive function.

30 depressed patients and 30 demographically matched healthy controls (HC) underwent MCCB cognitive assessment and 1H-MRS. After 8 weeks of vortioxetine medication, MCCB and 1H-MRS tests were retested in the MDD group. Before and after therapy, changes in cognitive performance, NAA/Cr, and Cho/Cr were examined in the MDD group.

Compared with the HC group, the MDD group had significant reduced in verbal learning, social cognition, and total cognition (all p < 0.05). And the MDD group had lower NAA/Cr in Right thalamus and Left PFC; the Cho/Cr in Right thalamus was lower than HC; the Cho/Cr in Left ACC had significantly increase (all p < 0.05). The MDD group showed significant improvements in the areas of verbal learning, attention/alertness, and total cognitive function before and after Vortioxetine treatment (all p < 0.05). The NAA/Cr ratio of the right PFC before and after treatment (t = 2.338, p = 0.026) showed significant changes.

Vortioxetine can enhance not just the depression symptoms of MDD patients in the initial period, but also their verbal learning, social cognition, and general cognitive capacities after 8 weeks of treatment. Furthermore, vortioxetine has been shown to enhance cognitive function in MDD patients by altering NAA/Cr and Cho/Cr levels in the frontal-thalamic-ACC.

Apathy is a prevalent and highly debilitating non-motor symptom of Parkinson's disease (PD) that is often overlooked in clinical practice due to its subtle nature. This review aims to provide a comprehensive overview of the current evidence for the treatment of apathy in PD, highlighting recent advancements and emerging therapeutic avenues. In this review, we analyse a diverse array of treatment strategies for apathy in PD, including pharmacological interventions, non-pharmacological approaches, and emerging neuromodulation techniques. We evaluate the efficacy, safety, and limitations of established pharmacotherapies, such as dopaminergic agents, antidepressants, and cognitive enhancers. Additionally, we examine the promising role of non-pharmacological interventions, encompassing psychotherapies and behavioural interventions, in ameliorating apathetic symptoms. Furthermore, this review explores the effects of neuromodulation techniques on apathy, including the modulation of apathy via deep brain stimulation and emerging data on the potential influence of transcranial magnetic stimulation (TMS) on apathy in PD. Ultimately, a deeper understanding of effective treatment strategies for apathy has the potential to significantly improve the quality of life and overall well-being of individuals living with PD.

Emotional symptoms are recognized as a key feature in individuals with major depressive disorder. Previously, emotional blunting has been described both as a side effect of antidepressant treatment and as a symptom of depression. Little is known about the change of emotional blunting during antidepressant treatment.

The PREDDICT trial is a randomized, placebo-controlled, 6-week trial on the augmentation of vortioxetine with the anti-inflammatory agent celecoxib or placebo. Presently we report on exploratory secondary outcomes of changes in emotional blunting in depression assessed with the Oxford Depression Questionnaire (ODQ) total score and subscores from baseline to 8-week, 3-month, and 6-month follow-up assessments.

In the whole group, there was a significant improvement in the ODQ total score and all subscores after 8 weeks. After stratification of participants into the treatment groups, the ODQ total score as well as subscores related to emotional blunting as a symptom of depression (reduction in positive emotions, not caring) improved between baseline and all follow-up time points in both treatment groups. Changes in subscores considered as a side effect of antidepressants (general reduction in emotions, emotional detachment) were inconclusive in both treatment groups. Overall, the placebo-augmented group showed slightly better results in changes of emotional blunting scores than the celecoxib group as did those with elevated inflammation at screening, regardless of treatment group.

This analysis suggests favorable effects of vortioxetine on emotional blunting in both short- and long-term course. The beneficial impact of vortioxetine on emotional blunting was weaker in celecoxib-augmented patients compared with placebo, possibly due to pharmacokinetic interactions. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p.

Anhedonia, a core diagnostic feature for major depressive disorder (MDD), is defined as the loss of pleasure and interest in daily activities. Its prevalence in MDD patients vary from 35 to 70%. Anhedonia in MDD negatively impacts functioning and is associated with treatment resistance and poorer prognosis for various clinical outcomes. Owing to its complexity, there remains considerable heterogeneity in the conceptualization, diagnosis and clinical management of anhedonia in MDD.

This modified Delphi panel was conducted to elicit expert opinion and establish consensus on concepts relating to clinical features, diagnosis and treatment of MDD with anhedonia (MDDwA) amongst psychiatrists in the Asia-Pacific region. Seven themes were covered. A three-stage process was adopted for consensus generation (two online survey rounds, followed by a moderated consensus meeting). Statements were developed based on a literature review and input from a steering committee of six regional experts. The panel included 12 psychiatrists practicing in Australia, China, Hong Kong, Japan, South Korea and Taiwan with ≥5 years of specialist clinical experience, including assessment or management of patients with MDDwA.

Overall, consensus was achieved (median ≥8) on 89/103 statements (86%). About half of the statements (55/103, 53%) achieved consensus in Round 1, and 29/36 modified statements achieved consensus in Round 2. At the moderated consensus meeting, five modified statements were discussed by the steering committee and consensus was achieved on all statements (5/5). The findings highlighted a lack of clear and practical methods in clinical practice for assessing anhedonia in MDD patients and limited physician awareness of anhedonia in Asia-Pacific.

Insights from this Delphi consensus provide a reference point for psychiatrists in Asia-Pacific to optimize their strategies for personalized diagnosis and management of patients with MDDwA. Identification of distinct and clinically relevant subtypes in MDD may be valuable for guiding personalized diagnosis and management approaches, including type-specific therapies.

Emotional blunting is a symptom that has always been present in depressed patients. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective supplementary therapy for treating depression. However, the effectiveness and brain imaging processes of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) in the treatment of depression with emotional blunting have not been observed in randomized controlled trials.

This study is a randomized, controlled, double-blind, and single-center clinical trial in which 80 eligible depressed patients with emotional blunting will be randomly assigned to two groups: a functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) group and a control group. Individuals in the fMRI-rTMS group (n = 40) will receive high-frequency rTMS (10 Hz, 120% MT). The main target of stimulation will be the area most relevant to the functional connectivity of the right medial prefrontal cortex (mPFC) and amygdala. The control group (n = 40) will receive sham stimulation, with a coil flipped to 90 degrees relative to the vertical scalp. All patients will receive 15 consecutive days of treatment, with each session lasting half an hour per day, followed by 8 weeks of follow-up. The primary outcome is the comparison of Oxford Depression Questionnaire (ODQ) scores between these two groups at different time points. The secondary outcomes include evaluating other clinical scales and assessing the differences in brain imaging changes between the two groups before and after treatment.

This trial aims to examine the effects of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) intervention on depressed patients experiencing emotional blunting and to elucidate the potential mechanism behind it. The results will provide new evidence for using fMRI-rTMS in treating depression with emotional blunting in the future.

ClinicalTrials.gov INCT05555940. Registered on 13 September 2022 at http://clinicaltrials.gov .

Vortioxetine is efficacious and well tolerated in patients with major depressive disorder (MDD) and is available as an immediate-release tablet and oral drop solution. The oral drop solution may offer clinical benefits versus a tablet, such as the reduced risk of nausea, personalised dosing and ease of administration.

To investigate the bioequivalence of vortioxetine 20 mg/mL oral drop solution versus a 20 mg immediate-release tablet.

Healthy adults were randomised 1:1 to receive vortioxetine 20 mg oral drop solution or immediate-release 20 mg tablet after fasting on days 1 and 29 in an open-label, single-centre, single-dose crossover study. The area under the plasma concentration-time curve from 0 to 72 h (AUC0-72h) and maximum plasma concentration (Cmax) were analysed. Bioequivalence was concluded if the 90% CI for the oral drop solution-to-immediate-release tablet ratio for AUC0-72h and Cmax were contained within a range of 0.80-1.25.

Vortioxetine oral drop solution was bioequivalent to the tablet (n = 26; estimated AUC0-72h ratio 1.06 (90% CI: 1.03-1.10); Cmax ratio 1.01 (90% CI: 0.97-1.05)). A similar proportion of participants reported adverse events in each study arm but more headache events (7 vs 1) were reported with the oral drop solution versus tablet. The most common adverse event was nausea (16-23% of participants; all mild intensity).

Vortioxetine oral drop solution is bioequivalent to immediate-release tablets. Oral drop solution provides an alternative to tablets and facilitates clinical benefit through individualised treatment, including gradual dose up-titration, for patients with MDD.

Depressive symptoms are a customary finding in hospitalized patients, particularly those who are undergoing long hospitalizations, underwent major surgical procedures or suffer from high levels of multimorbidity and frailty. The patients included in this case series shared high degrees of frailty-complexity and were evaluated within the ordinary consultation and liaison psychiatry service of the University Hospital in Pisa, Italy, from September 2021 to June 2023. Patients were administered at least one follow-up evaluation after a week and before discharge. To relate this case series to the extant literature, a comprehensive systematic review of vortioxetine safety and efficacy was performed. None of the six patients included developed serious safety issues, but one patient complained of mild-to-moderate nausea for some days after the vortioxetine introduction. Five out of six patients exhibited at least a slight clinical benefit as measured by the clinical global impression scale. Of the 858 entries screened via Scopus and Medline/PubMed, a total of 134 papers were included in our review. The present case series provides preliminary evidence for vortioxetine's safety in this healthcare domain. The literature reviewed in this paper seems to endorse a promising safety profile and a very peculiar efficacy niche for vortioxetine in consultation and liaison psychiatry.

Western medicine is beneficial for the recovery of neurological function in patients with depression, but some patients experience side effects such as headaches, dizziness, nausea, gastrointestinal symptoms, insomnia, and cardiac dysfunction. In recent years, integrative medicine has achieved positive results in the treatment of various diseases.

To study Chuanjin Qinggan decoction combined with selective serotonin reuptake inhibitors (SSRIs) in patients with herpes zoster complicated by depression.

Patients with herpes zoster complicated by depression who were treated at the Yantai Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were retrospectively selected as research participants. Among them, 43 patients with herpes zoster complicated by depression who received SSRI treatment between January and December 2021 were assigned to the Western medicine group, while those who received combined treatment of traditional Chinese and Western medicine between January and December 2022 were assigned to the combined group. Both groups were treated for eight weeks. The degree of pain, effect of herpes zoster treatment, degree of improvement in depressive symptoms, serum neurotransmitter levels, sleep quality, and occurrence of adverse reactions were compared between the two groups.

We found that after eight weeks of drug treatment, the two treatment schemes achieved differing efficacy. In further comparison, we found that, compared with patients treated with SSRIs alone, patients treated with Chuanjin Qinggan decoction combined with SSRIs showed more significant improvement in depression and a greater increase in dopamine and 5-hydroxytryptamine levels after treatment (P < 0.05). Patients treated with Chuanjin Qinggan decoction combined with SSRIs also experienced lower pain, better treatment efficacy for herpes zoster, better sleep quality, and a lower incidence of adverse reactions compared to those treated with SSRIs alone (P < 0.05). All minor adverse reactions occurring during treatment were resolved after symptomatic treatment.

The treatment scheme of Chuanjin Qinggan decoction combined with SSRIs can improve the psychological state of patients with herpes zoster complicated by depression and alleviate adverse reactions.

Originally developed in English, the Oxford Depression Questionnaire (ODQ) is a patient-reported scale specifically developed for assessing emotional blunting in people with major depressive disorder (MDD). We aimed to examine the reliability and validity of the Japanese version of the ODQ.

This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the ODQ and other clinical rating scales at baseline and Weeks 8, 12 and 24.

One hundred and sixteen patients initiated vortioxetine and had ≥1 post-baseline visit. Directionally, the associations between ODQ scores and other clinical measures were as expected and demonstrated good concurrent validity. Factor analysis shows that the scale has a good fit for three factors. The Cronbach's α coefficient was 0.912, and the scale also showed good test-retest reliability with intraclass correlation coefficients for the ODQ total score and domains ranging between 0.69 and 0.82. ODQ scores had strong positive correlations with symptom severity assessed using the Montgomery and Åsberg Depression Rating Scale and were moderately correlated with work productivity, overall functioning, and quality of life scales.

Data from this prospective analysis confirm that the Japanese version of the ODQ retains the good validity and reliability of the original English scale and is suitable for use in prospective studies wanting to capture treatment effects on emotional blunting in MDD.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most often used medications to treat major depressive disorder (MDD). Despite their effectiveness in reducing depressive symptoms, several issues are associated with their use in MDD, such as limited improvement of anhedonia, emergence of emotional blunting, induction or exacerbation of insomnia, and sexual dysfunction. Due to its also devoid of the issues related to treatment noted with SSRIs. The aim of this 12-week non-inferiority naturalistic observation was to compare the effectiveness and tolerability of SSRIs and trazodone in extended release (XR) in MDD. Methods: A total of 186 subjects were recruited, of which 92 received trazodone XR and 94 received SSRIs. Patients were allocated to trazodone XR or SSRIs, according to the attending physician based on clinical evaluation. Assessments at baseline and weeks 2, 4, 8, and 12 were conducted to evaluate the severity of depression (Montgomery-Åsberg Depression Rating Scale, clinician- and patient-rated Quick Inventory of Depressive Symptomatology-the primary endpoints of the study), anhedonia (the Snaith-Hamilton Pleasure Scale), anxiety (the Hamilton Anxiety Rating Scale), insomnia (the Athens Insomnia Scale), and therapeutic effectiveness (the Clinical Global Impression Scale). Results: After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of depression, anxiety, and insomnia. There was a trend for higher effectiveness of in reduction of anhedonia, which became insignificant after controlling the results for the duration of previous psychiatric treatment as a covariate. The proportion of treatment-responsive subjects in the trazodone XR group compared to SSRIs was comparable or higher. The proportion of patients achieving remission was higher in the trazodone XR arm vs. the SSRI arm. Discussion: In summary, the results indicate that trazodone XR is effective in MDD in the "real-world" setting. Its potential superiority over SSRIs in addressing particular symptomatic dimensions should be verified in future studies.

Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known.

We aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned fear.

We searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal experiments.

Meta-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect sizes.

This review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs.

Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

Despite frequent recognition of emotional blunting in the published literature, either as a primary symptom of depression or as an adverse effect of antidepressants, there is no systematic synthesis on this topic to our knowledge. We undertook this scoping review to assess the prevalence, clinical features, implicated causes and management of emotional blunting, outlining the phenomenological and clinical gaps in research.

A systematic search was done until March 15, 2022, to include all original studies (i.e., interventional trials, cohort & cross-sectional studies, case reports, and case series). All reviewed data were delineated to answer pertinent clinical, phenomenological, and management questions related to the phenomenon of emotional blunting.

A total of 25 original studies were included in our scoping review. Emotional blunting was described as a persistent diminution in both positive and negative feelings in depressed patients, who could subjectively differentiate it from their acute symptoms. However, the literature lacked the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants. Common clinical strategies to manage antidepressant-induced emotional blunting included dose reduction or switching to a different antidepressant.

Emotional blunting was a significant patient-reported concern with antidepressants. Future research should clarify phenomenological and neurobiological constructs underlying emotional blunting to improve diagnostic and management skills.

Cinnamon oil (CO) is a classic Chinese medicine with excellent soothing effects on exhaustion, weakness and depression. Cinnamaldehyde is the main active ingredient of cinnamic oil. Although CO have antidepression-like effects, limited information is available. Furthermore, the disadvantages of CO, such as low oral availability and difficult portability, limit its development. In this study, a Cinnamon Oil Solid Self-Microemulsifying Drug Delivery System (CO-S-SME) was designed, prepared. In addition, we explored the effects and mechanisms of CO-S-SME on chronic unpredictable mild stress (CUMS)-induced depression-like behavior, monoamine neurotransmitters, inflammatory factors, intestinal flora in mice. Mice were subjected CUMS to establish the depression model. The antidepressant effect of CO-S-SME was evaluated by behavioral tests. In addition, the expression levels of neurotransmitters, corticosterone (CORT) and inflammatory factors in CUMS mice were analyzed by enzyme-linked immunosorbent assay. In addition, we explored the effects of CO-S-SME on the diversity and richness of intestinal flora of mice in each group. Behavioral tests showed that CO-S-SME could effectively improve depression-like behaviors in CUMS mice. Specifically, CO-S-SME treatment effectively increased neurotransmitter levels and reduced the expressions of corticosterone and inflammatory factors in CUMS mice. CO-S-SME also changed the intestinal flora composition, decreased the ratio of Firmicutes to Bacteroidetes, reduced relative abundances of Lactobacillus, modulated Alpha diversity and beta diversity. These results suggest that CO-S-SME an act as a good antidepressant, exhibiting effects via monoamine neurotransmitters, CORT, inflammation cytokines, and intestinal flora.

Sirtuin 6 (SIRT6) is a nuclear silencing information regulator that is widely expressed in brain. Inhibition of SIRT6 in the brain induced antidepressant effects in rodents. However, SIRT6 knockout in neurons induced developmental retardation and cognitive impairments. In this study, a mouse strain of astrocyte conditional knockout SIRT6 (AKO) was constructed. Unlike whole brain SIRT6 knockout mice, AKO mice did not show growth retardation. We showed that SIRT6 knockout in astrocytes did not impair the learning and memory ability of mice. Chronic unpredictable mild stress (CUMS) was used to evaluate the anti-depression and anti-anxiety effects in mice. In tail suspension test and forced swimming test, AKO mice did not show depression like phenotype induced by CUMS. In addition, knockout of SIRT6 in astrocytes alleviated the high anxiety level induced by CUMS in light and dark box test, open field test and elevated cross maze test. Three box social test showed that the deletion of SIRT6 in astrocytes changed the social preference of mice. Re-expression of SIRT6 in astrocytes mediated by adeno-associated virus reversed the social preference of AKO mice, but the re-expression also eliminated the anti-depression and anti-anxiety effects in AKO mice. Deletion of SIRT6 in astrocytes change the purine metabolic homeostasis of medial prefrontal cortex in mice. The results of transcriptomics and metabolomics analysis showed that the deletion of SIRT6 would change the purine metabolic pathway of cultured astrocytes and increase the contents of inosine and the second messenger cyclic adenosine monophosphate in astrocytes. In conclusion, knockout of SIRT6 in astrocytes induced anti-depression and anti-anxiety effects in mice without impairing the development and cognitive ability of mice.

Major depressive disorder (MDD) is a debilitating mental disorder that can be treated with a number of different antidepressant therapies, each with its own unique prescribing considerations. Complicating the selection of an appropriate antidepressant for adults with MDD is the heterogeneity of clinical profiles and depression subtypes. Additionally, patient comorbidities, preferences, and likelihood of adhering to treatment must all be considered when selecting an appropriate therapy. With the majority of prescriptions being written by primary care practitioners, it is appropriate to review the unique characteristics of all available antidepressants, including safety considerations. Prior to initiating antidepressant treatment and when patients do not respond adequately to initial therapy and/or exhibit any hypomanic or manic symptoms, bipolar disorder must be ruled out, and evaluation for psychiatric comorbidities must be considered as well. Patients with an inadequate response may then require a treatment switch to another drug with a different mechanism of action, combination, or augmentation strategy. In this narrative review, we propose that careful selection of the most appropriate antidepressant for adult patients with MDD based on their clinical profile and comorbidities is vital for initial treatment selection.Strategies must be considered for addressing partial and inadequate responses as well to help patients achieve full remission and sustained functional recovery. This review also highlights data for MDD clinical outcomes for which gaps in the literature have been identified, including the effects of antidepressants on functional outcomes, sleep disturbances, emotional and cognitive blunting, anxiety, and residual symptoms of depression.

The Motivation and Energy Inventory (MEI) is a patient-reported scale for assessment of the impact of mental/cognitive energy, social motivation, and physical energy on daily functioning in patients with major depressive disorder (MDD). This analysis was undertaken to establish the clinically relevant response threshold for the MEI in patients with MDD receiving antidepressant treatment.

Patients with MDD experiencing inadequate response and emotional blunting on selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor monotherapy (adequate dose for ≥6 weeks) were switched to vortioxetine 10-20 mg/day for 8 weeks. Anchor- and distribution-based methods were used to determine the minimal clinically important difference (MCID) in MEI total score.

After 8 weeks of vortioxetine treatment, mean (standard deviation) change in MEI total score from baseline was 33.0 (27.3) points. At week 8, mean change in MEI total score from baseline was 37.5 (27.8) points in patients no longer reporting emotional blunting and 28.3 (26.2) points in those still experiencing emotional blunting. In patients considered minimally improved (i.e. Clinical Global Impression-Improvement [CGI-I] score of 3 after 8 weeks of vortioxetine), mean change in MEI total score from baseline was 14.7 (19.1) points. In patients defined as responders (CGI-I score of 2 at 8 weeks), mean change in MEI total score was 33.0 (24.7) points.

Short study duration.

These results provide further validation of the clinical utility of the MEI for assessing treatment response in patients with MDD. The suggested MCID for MEI total score is 15 points.

ClinicalTrials.gov identifier: NCT03835715.

Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient's disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult to diagnose, resulting in limited recognition and in undertreatment. The early detection and treatment of depression simultaneously with the neurological disorder is key to avoiding deterioration and further disability. Although the neurologist should be able to identify and treat depression initially, a neuropsychiatry team should be available for severe cases and those who are unresponsive to treatment. Neurologists should be also aware that in neurodegenerative diseases, such as Alzheimer's or Parkinson's, different depression symptoms could develop at different stages of the disease. The treatment options for depression in neurological diseases include drugs, cognitive-behavioral therapy, and somatic interventions, among others, but often, the evidence-based efficacy is limited and the results are highly variable. Here, we review recent research on the diagnosis and treatment of depression in the context of Alzheimer's disease, Parkinson's disease, and strokes, with the aim of identifying common approaches and solutions for its initial management by the neurologist.

Major Depressive Episodes (MDE) following COVID-19 are frequent, can have a characteristic clinical picture, and are associated with immune-inflammatory changes. Vortioxetine is known to improve physical and cognitive performance in patients with depression and shows anti-inflammatory and anti-oxidative activities. This study aimed to retrospectively evaluate the effects of vortioxetine after 1 and 3 months of treatment in 80 patients (44.4% males, 54±17.2 years) with post-COVID-19 MDE. The primary outcome was improvement in physical and cognitive symptoms measured by specific items of Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Short Form-36 Health Survey Questionnaire (SF-36), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire for Depression (PDQ-D5). Changes in mood, anxiety, anhedonia, sleep, and quality of life were also investigated, as well as the underlying inflammatory status. Results show that, alongside reduction of depressive symptoms (HDRS, p<0.001), vortioxetine (mean dose: 10.1±4.1 mg/day) significantly improved physical features (all measurements p<0.001) and cognitive functioning (DDST, p=0.02; PDQ-D5, p<0.001) throughout treatment. We also observed significant reductions in inflammatory indexes. Therefore, vortioxetine might be a favorable therapeutic choice in post-COVID-19 patients with MDE because of its beneficial effects on physical complaints and cognition, features that appear to be specifically affected in relation to SARS-CoV-2 infection, and its good safety/tolerability profile. High prevalence and clinical and socioeconomic implications of COVID-19 consequences are a major public health concern and developing tailored, safe interventions is crucial to promote full functional recovery.