Treatment Of Major Depressive Disorder Research Articles

Escin ameliorates CUMS-induced depressive-like behavior via BDNF/TrkB/CREB and TLR4/MyD88/NF-κB signaling pathways in rats

Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10mg/kg) or fluoxetine (2mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.

Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation for Depression: A Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD). To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD. This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo University, Lishui Second People's Hospital, and Taizhou Second People's Hospital). Adult patients (aged 18-65 years) who were diagnosed with major depressive disorder were recruited. Participants were randomly assigned to 1 of 4 interventions: active tDCS + active rTMS, sham tDCS + active rTMS, active tDCS + sham rTMS, and sham tDCS + sham rTMS. Data analysis followed an intention-to-treat approach. Patients received a 2-week course of treatment. The tDCS was administered using a 2-mA direct current stimulator with electrodes placed on the left and right dorsolateral prefrontal cortex (DLPFC). Each tDCS session lasted 20 minutes and was conducted 30 to 60 minutes prior to the rTMS session for a total of 10 sessions. The rTMS was delivered at a frequency of 10 Hz using a figure-8 coil placed on the left DLPFC, with each session consisting of 1600 pulses. Treatments were administered 5 times per week for 2 weeks. Sham treatments were performed with a pseudostimulation coil and emitted only sound. The primary outcome was the change in total score from baseline to week 2 on the 24-item Hamilton Depression Rating Scale (HDRS-24; score range: 0-52, with the highest score indicating more severe symptoms). A total of 240 participants (139 females [57.9%]; mean [SD] age, 32.50 [15.18] years) were included. As a primary outcome, patients who received active tDCS + active rTMS showed a significantly greater reduction in mean (SD) HDRS-24 total scores compared with patients in the other 3 groups (active tDCS + active rTMS: 18.33 [5.39], sham tDCS + active rTMS: 14.86 [5.59], active tDCS + sham rTMS: 9.21 [4.61], and sham tDCS + sham rTMS: 10.77 [5.67]; F3,236 = 35.79; η2 = 0.31 [95% CI, 0.21-0.39]; P < .001). This trial found that tDCS + rTMS was a more effective and safe treatment option than either the tDCS or rTMS intervention alone for patients with MDD. China Clinical Trial Registry Identifier ChiCTR2100052122.

Aperiodic (1/f) neural activity robustly tracks symptom severity changes in treatment-resistant depression.

A reliable physiological biomarker for Major Depressive Disorder is essential for developing and optimizing neuromodulatory treatment paradigms. This study investigates a passive electrophysiologic biomarker that tracks changes in depressive symptom severity on the order of minutes to hours. We analyze brief recordings from intracranial electrodes implanted deep in the brain during a clinical trial of deep brain stimulation for treatment-resistant depression in 5 human subjects (nfemale= 3, nmale = 2). This surgical setting allows for precise temporal and spatial sensitivity in the ventromedial prefrontal cortex, a challenging area to measure. We focused on the aperiodic slope of the power spectral density, a metric reflecting the balance of activity across all frequency bands and serving as a proxy for excitatory/inhibitory balance in the brain. Our findings demonstrate that shifts in aperiodic slope correlate with depression severity, with flatter (less negative) slopes indicating reduced depression severity. This significant correlation was observed in all N=5 subjects, particularly in the ventromedial prefrontal cortex. This biomarker offers a new way to track patient responses to Major Depressive Disorder treatment, paving the way for individualized therapies in both intracranial and non-invasive monitoring contexts.

Prevalence of major depression, suicidal ideation, and mental health treatment among cancer survivors.

Cancer diagnosis and treatment can result in a significant psychological burden. This study sought to investigate the prevalence of major depression, associated treatments, and suicidal ideation in cancer survivors compared to a non-cancer cohort. This is a retrospective, population-based study using survey responses from the National Survey on Drug Use and Health collected from January 2015 to December 2019. Survey data sets were queried for all respondents who provided a cancer history. Respondents with a reported history of cancer ("cancer survivors") were further stratified by whether they reported a "recent" cancer diagnosis within the past 12 months. Survey responses were evaluated for recent diagnoses of and treatments for major depressive disorder and suicidal ideation. Among the 212,411 survey respondents identified, 7,635 (3.6%) reported a cancer history, with 1,486 (0.7%) reporting a recent cancer history. There were no differences in prevalence of major depression between cancer survivors and participants without cancer (9.3% vs 9.2%, p = 0.762), though the prevalence was slightly higher among recent cancer survivors (10.0% vs 9.2%, p = 0.259). Among respondents diagnosed with major depression, cancer survivors were significantly more likely to receive treatment for depression (78.6% vs 60.3%, p < 0.001). Suicidal ideation was significantly lower among cancer survivors (5.1% vs 6.2%, p < 0.001) including recent survivors (5.0% vs 6.2%, p < 0.001). There was no overall difference in the prevalence of major depression between cancer survivors and respondents without cancer. Survivors with major depression were more likely to receive treatments. Prevalence of major depression was higher in recent cancer survivors.

Prediction of electroconvulsive therapy outcome: A network analysis approach.

While electroconvulsive therapy (ECT) for the treatment of major depressive disorder is effective, individual response is variable and difficult to predict. These difficulties may in part result from heterogeneity at the symptom level. We aim to predict remission using baseline depression symptoms, taking the associations among symptoms into account, by using a network analysis approach. We combined individual patient data from two randomized controlled trials (total N = 161) and estimated a Mixed Graphical Model to estimate which baseline depression symptoms (corresponding to HRSD-17 items) uniquely predicted remission (defined as either HRSD≤7 or MADRS<10). We included study as moderator to evaluate study heterogeneity. For symptoms directly predictive of remission we computed odds ratios. Three baseline symptoms were uniquely predictive of remission: suicidality negatively predicted remission (OR = 0.75; bootstrapped confidence interval (bCI) = 0.44-1.00) whereas retardation (OR = 1.21; bCI = 1.00-2.02) and hypochondriasis (OR = 1.31; bCI = 1.00-2.25) positively predicted remission. The estimated effects did not differ across trials as no moderation effects were found. By using a network analysis approach this study identified that the presence of suicidal ideation predicts an overall worse treatment outcome. Psychomotor retardation and hypochondriasis, on the other hand, seem to be associated with a better outcome.

A pooled analysis of the efficacy of sertraline in women, with a focus on those of childbearing age

IntroductionGender- and age-specific research on medications is essential for personalizing treatment plans, optimizing dosing, minimizing adverse effects and improving outcomes. Women are twice as likely to be diagnosed with major depressive disorder (MDD), and it is commonly reported during their reproductive years. This post-hoc pooled analysis evaluated the efficacy of sertraline (one of the most studied medications in women) in women of reproductive age (18–44 years).MethodsData was pooled from nine clinical trials of sertraline that included 1832 subjects with MDD. The analysis set included 1097 women, 651 of those were of reproductive age. Sertraline was compared with placebo for changes in total HAM-D17 and CGI scores measured over time through MMRM analysis. The change from baseline to the end of study (-week 8) was assessed using ANCOVA.ResultsThe changes from baseline in total HAM-D17 and CGI scores were significantly higher for sertraline than for placebo at the end of 8 weeks for all women (LS Mean difference, 95% CI: -1.81(-3.01,-0.62), P = 0.0029; -0.38(-0.55,-0.20), P < 0.0001, respectively). For women of reproductive age these changes (LS Mean difference, 95% CI: -2.08(-3.52,-0.64), P = 0.0047; -0.44(-0.66,-0.22), P < 0.0001, respectively), were significant from week 2 (HAM-D17) and week 1 (CGI) till the end of study.LimitationsOnly sertraline and placebo arms were included in the analysis. The dosing varied between studies, and the effect of dose was not addressed.ConclusionsSertraline is an effective option for treatment of MDD in women, including those in the childbearing age.

Depression and metabolic connectivity: insights into the locus coeruleus, HF-rTMS, and anxiety

The use of repetitive Transcranial Magnetic Stimulation (rTMS) in treating major depressive disorder (MDD) is increasingly being explored in precision medicine. However, there’s a notable lack of understanding of the underlying neurobiological effects, which limits our ability to correlate specific imaging features with treatment efficacy. As one possible neurobiological mechanism, clinical research has already shown that in MDD, lower norepinephrine release in the locus coeruleus (LC) triggers depressive symptoms, and pharmacological approaches that block norepinephrine reuptake boost its levels, easing depression. Surprisingly, the LC has not received a more pronounced focus in contemporary rTMS research. This study investigates the role of the LC in MDD and its response to high-frequency (HF)-rTMS using 18FDG-PET imaging. We compared LC metabolic connectivity between MDD patients (n = 43) and healthy controls (n = 32). Additionally, we evaluated the predictive value of LC connectivity for HF-rTMS treatment outcomes and examined post-treatment changes in LC metabolic connectivity. Our findings revealed significant differences in LC metabolic connectivity between MDD patients and controls. Baseline LC metabolic connectivity did not predict HF-rTMS treatment outcomes. However, post-treatment analyses showed a significant correlation between improved clinical outcomes and attenuation of LC metabolic connectivity in regions associated with cognitive control and the default mode network. Notably, a reduction in state anxiety moderated this relationship, highlighting the role of anxiety in HF-rTMS efficacy for MDD treatment. Our findings suggest that LC metabolic connectivity, influenced by state anxiety levels, may be crucial in HF-rTMS efficacy, offering further insights for personalized MDD treatment strategies.

Adenosine regulates depressive behavior in mice with chronic social defeat stress through gut microbiota

Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation.

Safety and efficacy of individual target transcranial magnetic stimulation to stimulate the most negative correlate of DLPFC-pgACC in the treatment of major depressive disorder: study protocol of a double-blind, randomised controlled trial

IntroductionMajor depressive disorder (MDD) is a common mental disorder that is characterised by high morbidity, high rates of relapse, high rates of disability and, in severe cases, suicide ideas or...

Glutamatergic Modulators for Major Depression from Theory to Clinical Use.

Major depressive disorder (MDD) is a chronic, burdensome, highly prevalent disease that is characterized by depressed mood and anhedonia. MDD is especially burdensome as approved monoamine antidepressant treatments have weeks-long delays before clinical benefit and low remission rates. In the past 2decades, a promising target emerged to improve patient outcomes in depression treatment: glutamatergic signaling. This narrative review provides a high-level overview of glutamate signaling in synaptogenesis and neural plasticity and the implications of glutamate dysregulation in depression. Based on this preclinical evidence implicating glutamate in depression and the rapid improvement of depression with ketamine treatment in a proof-of-concept trial, a range of N-methyl-D-aspartate (NMDA)-targeted therapies have been investigated. While an array of treatments has been investigated in registered phase 2 or 3 clinical trials, the development of most of these agents has been discontinued. Multiple glutamate-targeted antidepressants are actively in development, and two are approved. Nasal administration of esketamine (Spravato®) was approved by the US Food and Drug Administration (FDA) in 2019 to treat adults with treatment-resistant depression and in 2020 for adults with MDD with acute suicidal ideation or behavior. Oral combination dextromethorphan-bupropion (AXS-05, Auvelity® extended-release tablet) was FDA approved in 2022 for the treatment of MDD in adults. These approvals bolster the importance of glutamate in depression and represent an exciting breakthrough in contemporary psychiatry, providing new avenues of treatment for patients as first-line therapy or with either poor response or unacceptable side effects to monoaminergic antidepressants.

Review of Guidelines on Bupropion for Depression

What Is the Issue? Bupropion is a drug used in the treatment of depression. Bupropion is 1 of many treatment options available for depression and is associated with several side effects as well as the potential for misuse. Some patients continue to experience symptoms of depression despite trying multiple medications (known as treatment-resistant depression). Therefore, it is important to determine the place in therapy of bupropion for the treatment of depression. What Did We Do? To help determine the potential place in therapy for bupropion for the treatment of major depressive disorder (MDD) and treatment-resistant depression in adults, we sought to identify and summarize recommendations in evidence-based guidelines. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included publications, and narratively summarized the findings. What Did We Find? We identified 4 evidence-based guidelines that included recommendations on the use of bupropion for MDD. We identified 1 evidence-based guideline that included a recommendation on the use of bupropion for difficult-to-treat depression (defined as persistent depression despite several standard treatments). All 4 included guidelines recommend bupropion for the treatment of adults with MDD. Two of the guidelines recommend bupropion as a first-line treatment option. One guideline suggests bupropion as an option for initial pharmacologic treatment or for patients who have previously responded well to pharmacotherapy. One guideline suggests bupropion as an option for adjunctive treatment for patients in the acute phase of moderate to severe MDD who did not respond to treatment with a second-generation antidepressant. One guideline suggests bupropion as a second-line adjunctive option for adults with difficult-to-treat depression. What Does It Mean? The included evidence-based guidelines consistently recommend bupropion as an option for the treatment of adults with MDD. Additional factors such as the availability of other options, costs, and patient preferences may also be important to decision-making around the use of bupropion for MDD. Only 1 of the included guidelines included a recommendation on the use of bupropion for patients with difficult-to-treat depression. Future evidence-based guidelines that include recommendations on the use of bupropion for treatment-resistant depression would help fill the gaps identified in this report.

A personalised nutrition intervention for adolescent depression: a mixed-methods feasibility pilot study.

Randomised controlled trials have demonstrated the benefit of diet modification to improve diet quality in the treatment of adult major depressive disorder (MDD). However, research examining nutritional interventions for adolescents with MDD is sparse. This pilot study examined the feasibility of a personalised nutrition intervention for adolescents with MDD. Ten adolescents with MDD and their parents recruited from a tertiary care setting participated in an 8-week, single-arm mixed-methods study. Feasibility was assessed using five criteria (demand, acceptability, implementation, adaptation and limited efficacy testing) alongside qualitative interviews. The intervention involved four bi-weekly virtual nutrition counselling sessions with a stepped approach to dietary change, menu planning, grocery delivery and educational eHealth messages. Study participants sought positive changes in diet, health and lifestyle for adolescents and family-wide benefits. Recruitment challenges included concerns about managing mood fluctuations, anticipated dietary restrictions and the potential time and effort required for diet adherence. Feedback based on interviews emphasised moderate to high acceptability, satisfaction with menu planning and counselling and recognition of the benefits of trying new foods and sustaining positive dietary changes beyond the study. Improvements in depression symptoms (Cohen's d = 0·36, 95 % CI (-0·24, 3·36)), parent food modeling (Cohen's d = 0·24, 95 % CI (-0·43, 1·16) and the family food environment (Cohen's d = 0·61, 95 % CI (-0·04, 2·61)) were observed. This nutrition intervention was feasible for adolescents with MDD and was acceptable to both parents and depressed adolescents. These preliminary data suggest that further examination of the intervention and its potential benefits on depression symptoms and family food dynamics are warranted.

Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé.

Major depressive disorder (MDD) is associated with cognitive impairments that persist despite successful treatment. Transcranial magnetic stimulation is a noninvasive treatment for MDD that is associated with small procognitive effects on working memory and executive function. We hypothesized that pairing stimulation with N-methyl-D-aspartate (NMDA) receptor agonism would enhance the effects of stimulation and its procognitive effects. The effect of NMDA receptor agonism (D-cycloserine, 100 mg) on cognitive performance was tested in two randomized double-blind placebo-controlled trials: (1) acute effects of in the absence of stimulation (n = 20 healthy participants) and (2) a treatment study of individuals with MDD (n = 50) randomized to daily intermittent theta-burst stimulation (iTBS) with placebo or D-cycloserine for 2 weeks. Cognitive function was measured using the THINC-it battery, comprised of the Perceived Deficits Questionnaire, the Choice Reaction Time, the Trail Making Test, the Digit Symbol Substitution Test, and the 1-Back tests. D-cycloserine had no acute effect on cognition compared to placebo. iTBS + D-cycloserine was associated with significant improvements in subjective cognitive function and correct responses on the 1-Back when compared to iTBS + placebo. Improvements in subjective cognition paralleled depressive symptoms improvement, however 1-Back improvements were not attributable to improvement in depression. An intersectional strategy pairing iTBS with NMDA receptor agonism may restore cognitive function in MDD.

A prediction model for electroconvulsive therapy effectiveness in patients with major depressive disorder from the Dutch ECT Consortium (DEC).

Reliable predictors for electroconvulsive therapy (ECT) effectiveness would allow a more precise and personalized approach for the treatment of major depressive disorder (MDD). Prediction models were created using a priori selected clinical variables based on previous meta-analyses. Multivariable linear regression analysis was used, applying backwards selection to determine predictor variables while allowing non-linear relations, to develop a prediction model for depression outcome post-ECT (and logistic regression for remission and response as secondary outcome measures). Internal validation and internal-external cross-validation were used to examine overfitting and generalizability of the model's predictive performance. In total, 1892 adult patients with MDD were included from 22 clinical and research cohorts of the twelve sites within the Dutch ECT Consortium. The final primary prediction model showed several factors that significantly predicted a lower depression score post-ECT: higher age, shorter duration of the current depressive episode, severe MDD with psychotic features, lower level of previous antidepressant resistance in the current episode, higher pre-ECT global cognitive functioning, absence of a comorbid personality disorder, and a lower level of failed psychotherapy in the current episode. The optimism-adjusted R² of the final model was 19%. This prediction model based on readily available clinical information can reduce uncertainty of ECT outcomes and hereby inform clinical decision-making, as prompt referral for ECT may be particularly beneficial for individuals with the above-mentioned characteristics. However, despite including a large number of pretreatment factors, a large proportion of the variance in depression outcome post-ECT remained unpredictable.

Use of passively collected actigraphy data to detect individual depressive symptoms in a clinical subpopulation and a general population.

The presentation of major depressive disorder (MDD) can vary widely due to its heterogeneity, including inter- and intraindividual symptom variability, making MDD difficult to diagnose with standard measures in clinical settings. Prior work has demonstrated that passively collected actigraphy can be used to detect MDD at a disorder level; however, given the heterogeneous nature of MDD, comprising multiple distinct symptoms, it is important to measure the degree to which various MDD symptoms may be captured by such passive data. The current study investigated whether individual depressive symptoms could be detected from passively collected actigraphy data in a (a) clinical subpopulation (i.e., moderate depressive symptoms or greater) and (b) general population. Using data from the National Health and Nutrition Examination Survey, a large nationally representative sample (N = 8,378), we employed a convolutional neural network to determine which depressive symptoms in each population could be detected by wrist-worn, minute-level actigraphy data. Findings indicated a small-moderate correspondence between the predictions and observed outcomes for mood, psychomotor, and suicide items (area under the receiver operating characteristic curve [AUCs] = 0.58-0.61); a moderate-large correspondence for anhedonia (AUC = 0.64); and a large correspondence for fatigue (AUC = 0.74) in the clinical subpopulation (n = 766); and a small-moderate correspondence for sleep, appetite, psychomotor, and suicide items (AUCs = 0.56-0.60) in the general population (n = 8,378). Thus, individual depressive symptoms can be detected in individuals who likely meet the criteria for MDD, suggesting that wrist-worn actigraphy may be suitable for passively assessing these symptoms, providing important clinical implications for the diagnosis and treatment of MDD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial.

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.07 ± 2.73). A total of 174 participants (120 women, 54 men) were randomized to active (n = 87, mean age = 37.09 ± 11.14 years) or sham (n = 87, mean age = 38.32 ± 10.92 years) treatment. tDCS consisted of five sessions per week for 3 weeks then three sessions per week for 7 weeks in a 10-week trial, followed by a 10-week open-label phase. Each session lasted 30 min; the anode was placed over the left dorsolateral prefrontal cortex and the cathode over the right dorsolateral prefrontal cortex (active tDCS 2 mA and sham tDCS 0 mA, with brief ramp up and down to mimic active stimulation). As the primary outcome, depressive symptoms showed significant improvement when measured using the Hamilton Depression Rating Scale: active 9.41 ± 6.25 point improvement (10-week mean = 9.58 ± 6.02) and sham 7.14 ± 6.10 point improvement (10-week mean = 11.66 ± 5.96) (95% confidence interval = 0.51-4.01, P = 0.012). There were no differences in discontinuation rates. In summary, a 10-week home-based tDCS treatment with remote supervision in MDD showed high efficacy, acceptability and safety. ClinicalTrials.gov registration: NCT05202119.

Cost-effectiveness of screening and treating alcohol use and depression among people living with HIV in Zimbabwe: a mathematical modeling study

BackgroundAlcohol use disorder (AUD) and major depressive disorder (MDD) drive HIV transmission in many sub-Saharan African settings. The impact of screening and treating AUD and MDD on HIV outcomes is unknown. We aimed to identify the cost-effectiveness of AUD and MDD interventions in Zimbabwe, and their potential contribution to reaching Zimbabwe’s Ending the HIV Epidemic 2030 goal.MethodsUsing a validated HIV compartmental transmission model in Zimbabwe, we compared four policy scenarios: prevention as usual (baseline); implement AUD screening (using AUDIT) and treatment (motivational interviewing and cognitive-behavioral therapy); implement MDD screening (using PHQ-9) and treatment (cognitive-behavioral therapy); and implement screening and treatment for both. Outcomes were HIV incidence projections, infections averted through 2030, quality-adjusted life-years gained, cost per infection averted, and cost per QALY gained. Analyses considered “spillover,” when treatment for AUD also results in an improvement in MDD and the converse. Sensitivity analyses identified cost reductions necessary for AUD and MDD interventions to be as cost-effective as other HIV interventions, particularly the scale-up of long-acting PrEP.ResultsAUD and MDD combined will be responsible for 21.1% of new HIV infections in Zimbabwe by 2030. Without considering spillover, compared to the baseline, MDD intervention can reduce new infections by 5.4% at $2039/infection averted and $3186/QALY. AUD intervention can reduce new infections by 5.8%, but at $2,968/infection averted and $4753/QALY, compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.1% at $2810/infection averted and $4229/QALY, compared to baseline. Considering spillover, compared to the baseline, MDD intervention can reduce new infections by 6.4% at $1714/infection averted and $2630/QALY. AUD intervention can reduce new infections by 7.4%, but at $2299/infection averted and $3560/QALY compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.9% at $2247/infection averted and $3382/QALY compared to baseline. For MDD intervention to match the cost-effectiveness of scaling long-acting PrEP, the cost of MDD intervention would need to be reduced from $16.64 to $12.88 per person.ConclusionsImplementing AUD and MDD interventions can play an important role in HIV reduction in Zimbabwe, particularly if intervention cost can be decreased while preserving effectiveness.

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

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

Addressing Mental Health in Rural Settings: A Narrative Review of Blueberry Supplementation as a Natural Intervention.

Depression and anxiety are major public health issues; however, there is an unmet need for novel, effective, and accessible treatments, particularly in rural communities. Blueberries are an unexplored nutraceutical for these conditions due to their excellent nutritional profile, with particularly high levels of polyphenols and anthocyanins and benefits on mood, cognition, and health. Here, we present a narrative review of the literature concerning the etiology and treatments of major depressive disorder (MDD) and generalized anxiety disorder (GAD). In both animal and human studies, blueberry supplementation can ameliorate behavioral symptoms of both anxiety and depression. The mechanistic underpinnings of these behavioral improvements are not fully defined, but likely involve biochemical alterations in the gut-brain axis, including to inflammatory cytokines, reactive oxygen species, and growth factors. We also review the limitations of traditional therapies in rural settings. Finally, we assess the potential benefit of nutraceutical interventions, particularly blueberries, as novel therapeutics for these distinct, yet related mental health issues.

A double-blind, placebo-controlled, randomised withdrawal study of adjunctive brexpiprazole maintenance treatment for major depressive disorder.

To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo). This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints. 1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole n = 240; ADT + placebo n = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; p = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C. Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.ClinicalTrials.gov identifier: NCT03538691. Funding: Otsuka, Lundbeck.