A Randomized Controlled Trial Comparing the Quality of Life and Medication Adherence in Patients on Antidepressant Monotherapy.

Background and objectives The quality of life declines with the growing severity of major depressive disorder (MDD). In depressed people, medication adherence and the quality of life are mutually corrosive. These concerns spurred the investigation of relationships between treatment outcomes and adherence levels. Limited studies are looking at how vortioxetine, escitalopram, and vilazodone affect these parameters. We aimed to detect how the Short Form-36 (SF-36) had changed 16 weeks after the baseline. The connection between treatment results (as expressed by the Hamilton Depression Rating Scale or HDRS) and medication adherence (as reflected by the Morisky Medication Adherence Scale-8 or MMAS-8) was also explored. Methods An open-label, randomized, three-arm trial with 96 MDD patients was conducted. For 16 weeks, the participants were put into three groups per a 1:1:1 ratio and administered tablets of vilazodone (20-40 mg/day), escitalopram (10-20 mg/day), or vortioxetine (5-20 mg/day). There were two test drugs: vilazodone and vortioxetine; the control was escitalopram. Four weeks apart, follow-up appointments were set after the baseline visit. The HDRS, mental and physical components of SF-36, and MMAS-8 scores were evaluated in the per-protocol (PP) population. Reduced HDRS scores were indicative of improved depression symptoms. Higher MMAS-8 and SF-36 scores indicated high drug adherence and enhanced quality of life. Our analysis used the Kruskal-Wallis test, the Bonferroni correction, and the Sankey diagram. In the Clinical Trial Registry-India (CTRI), we recorded this study prospectively (2022/07/043808). Results One hundred nine (81.34%) of the 134 individuals we examined were eligible. The PP population consisted of 96 (88.07%) of them who wrapped up the 16-week study. The mean age of the group was 46.3 ± 6.2 years. For each of the three groups, the SF-36 physical component scores revealed a median difference of 24.5 (23.8-26.0), 24.0 (22.8-25.3), and 27.0 (25.0-29.0) (p = 0.001). Accordingly, the mental components of their SF-36 scores showed a median difference of 32.0 (31.0-33.3), 31.0 (29.8-34.3), and 36.0 (33.0-38.0) (p = 0.001). A median difference of -15.0 (-16.0 to -14.0), -16.0 (-17.0 to -15.0), and -16.0 (-17.0 to -15.8) was observed in the HDRS scores after 16 weeks, with respect to the baseline (p < 0.001). The median MMAS-8 scores at 16 weeks were 6.0 (6.0-7.0), 6.8 (6.0-7.0), and 7.5 (6.5-8.0) (p = 0.031). The Sankey diagram illustrated the connection between better treatment results, increased medication compliance, and decreased symptoms of depression. Conclusion In comparison to vilazodone and escitalopram, vortioxetine demonstrated a statistically significant decrease in HDRS scores and an improvement in the physical and mental component scores of the SF-36. Clinical improvements were evident in the individuals' drug adherence levels. Larger-scale studies are advised to investigate the effects of these medications on the quality of life, medication adherence, and treatment outcomes.

A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy.

BACKGROUND AND OBJECTIVES: The majority of mainstream antidepressants lack the promise of complete amelioration of symptoms. Other pitfalls include the latency period and side effects. These issues prompted investigations concerning the various roles of serotonin (5-HT) neurotransmissions in the etiology of depression. In this study, each study participant received vilazodone, vortioxetine, and escitalopram monotherapy for major depressive disorder (MDD) for 16 weeks. After that, the subject's scores on the Hamilton Depression Rating Scale (HDRS)-17 item version and the Montgomery Åsberg Depression Rating Scale (MADRS) were evaluated. In the study population, we kept track of the incidence of adverse events. METHODS: Ninety-six patients with MDD participated in this open-label, randomized, three-arm study. Participants were allotted into three groups according to a 1:1:1 ratio and given vilazodone (20-40 mg/day), vortioxetine (5-20 mg/day), or escitalopram (10-20 mg/day) for 16 weeks. Vortioxetine and vilazodone are test medications, with escitalopram serving as the control. After the baseline visit, follow-up appointments were scheduled every four weeks. Per-protocol (PP) and intent-to-treat (ITT) populations served as means for efficacy and safety evaluations, respectively. We prospectively registered this research in the Clinical Trial Registry, India (CTRI) (2022/07/043808). RESULTS: Out of the 134 patients we screened, 109 (81.34%) were eligible. Ninety-six (88.07%) of them completed the 16-week trial. In the PP population (n = 96), we analyzed efficacy. They had a mean age of 46.3 ± 6.2 years. At baseline, each group's median HDRS score was 30.0 (p = 0.964). Following 16 weeks of antidepressant therapy, these scores dropped to 15.0, 14.0, and 13.0 (p = 0.002). Baseline MADRS scores for all groups were 36.0 (p = 0.741). They had corresponding values of 20.0, 18.0, and 17.0 at 16 weeks (p < 0.001). Regarding both efficacy endpoints, the post-hoc analysis with the Bonferroni correction demonstrated statistically significant differences (p < 0.001). We performed the safety assessments within our ITT population (n = 109). Ninety-six adverse events were recorded. Nonetheless, none of them seemed serious. Still, five participants opted out because of their side effects. Vomiting and nausea were the most frequent side effects. CONCLUSION: Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further.

Exploring the Role of Serum Hydrogen Sulphide (H2S) Levels in Manic Depressive Psychosis in Terms of Its Association, Diagnostic Ability, and Severity Prediction: Findings From a Tertiary Care Center in North Bengal.

INTRODUCTION: Manic depressive psychosis (MDP) or bipolar disorder, a prevalent psychiatric condition globally and in the Indian population, has been attributed to various pathological mechanisms. Hydrogen sulphide (H2S), a member of the gasotransmitter family, may be linked to the development of bipolar disorder because it plays a crucial role in maintaining proper neuronal function in terms of excitability, plasticity, and homeostatic functions. There is very little data regarding the role of the gasotransmitter H2S in MDP in terms of its association, diagnostic ability, and severity prediction, which led us to conduct this study among MDP patients in the Sub-Himalayan region of West Bengal. METHODS: This was an observational case-control study performed in the Department of Biochemistry, North Bengal Medical College and Hospital, Siliguri, West Bengal, India, from January 2022 to December 2022. Fifty diagnosed MDP patients and 50 healthy age- and sex-matched control subjects satisfying the inclusion and exclusion criteria were studied. The H2S level in the blood was assayed using the standardised spectrophotometric methylene blue method. The severity of depression was assessed by Hamilton Depression Rating Scale (HAM-D) scoring. RESULTS: Of the 50 MDP patients, 45 (90%) were in the depressive phase, and five (10%) were in the manic phase. Of the 45 depressive patients, eight (17.8%) had mild depression, 12 (26.7%) had moderate depression, 19 (42.2%) had severe depression, and six (13.3%) had very severe depression. The mean H2S level in MDP patients (41.98±18.88 µmol/l) was significantly (P<0.05) lower than that in control subjects (99.20± 15.20 µmol/l). It was also observed that the mean H2S level in MDP patients decreased with the duration of the disease but was not statistically significant. The mean H2S levels in the different depression severity groups were found to be significantly different (P<0.001). Receiver operating characteristic (ROC) curve analysis revealed that a cut-off value of H2S <78.5 µmol/l was associated with MDP, with a sensitivity of 96% and a specificity of 88%, and a cut-off value of H2S < 53 µmol/l predicted the severity of depression with a sensitivity of 89.3% and a specificity of 76.5%. CONCLUSION: The significant association of the gasotransmitter H2S in MDP patients and its role as a diagnostic and severity predictive marker can help us to employ proper measures for better management of MDP and improving quality of life.

Hyperarousal-state of Insomnia Disorder in Wake-resting State Quantitative Electroencephalography.

Objective: : Insomnia is associated with elevated high-frequency electroencephalogram power in the waking state. Although affective symptoms (e.g., depression and anxiety) are commonly comorbid with insomnia, few reports distinguished objective sleep disturbance from affective symptoms. In this study, we investigated whether daytime electroencephalographic activity explains insomnia, even after controlling for the effects of affective symptoms. Methods: : A total of 107 participants were divided into the insomnia disorder (n = 58) and healthy control (n = 49) groups using the Mini-International Neuropsychiatric Interview and diagnostic criteria for insomnia disorder. The participants underwent daytime resting-state electroencephalography sessions (64 channels, eye-closed). Results: : The insomnia group showed higher levels of anxiety, depression, and insomnia than the healthy group, as well as increased beta [t(105) = -2.56, p = 0.012] and gamma [t(105) = -2.44, p = 0.016] spectra. Among all participants, insomnia symptoms positively correlated with the intensity of beta (r = 0.28, p ＜ 0.01) and gamma (r = 0.25, p ＜ 0.05) spectra. Through hierarchical multiple regression, the beta power showed the additional ability to predict insomnia symptoms beyond the effect of anxiety (ΔR2 = 0.041, p = 0.018). Conclusion: : Our results showed a significant relationship between beta electroencephalographic activity and insomnia symptoms, after adjusting for other clinical correlates, and serve as further evidence for the hyperarousal theory of insomnia. Moreover, resting-state quantitative electroencephalography may be a supplementary tool to assess insomnia.

Cariprazine Augmentation in Treatment-Resistant Bipolar Depression: Data from a Retrospective Observational Study.

BACKGROUND: Treatment-resistant bipolar depression is one of the leading problems in psychiatry with serious consequences on patients functioning, quality of life and resource utilization. Despite this, there is a lack of consensus on diagnostic criteria and treatment algorithms. OBJECTIVE: The objective of the present study is to assess the acute effectiveness and tolerability of cariprazine in the management of treatment resistant bipolar depression. METHODS: This is a four weeks retrospective multicentric observational study on patients with treatment resistant bipolar depression receiving cariprazine in augmentation to the current treatment. Cariprazine dosage changed during the follow-up period according to clinical judgment. Since data followed a non-normal distribution, non-parametric tests were used to pursue the analysis. The effectiveness of cariprazine was assessed through the mean change in Hamilton Depression rating scale (HAM-D) scores from baseline to endpoint. For missing values, a "Last Observation Carried Forward" approach was applied. RESULTS: Fifty-one patients were enrolled. Four patients (7.8%) discontinued cariprazine mainly due to adverse events. Mean cariprazine dose was 1.7 mg/day. The mean HAM-D score decreased significantly from baseline (T0) to week 4 (T4) at each evaluation point. Fourty-five one percent of the patients benefited of cariprazine add-on strategy: 23.5% achieved a clinical response and 21.6% were remitters. Among the completers, 70.6% experienced at least one adverse event. All side effects were mild to moderate. CONCLUSION: Cariprazine seems to be an effective and well tolerated option in the management of patients with treatment resistant bipolar depression.

Optimal risk and diagnosis assessment strategies in perinatal depression: A machine learning approach from the life-ON study cohort.

This study aimed to assess the concordance of various psychometric scales in detecting Perinatal Depression (PND) risk and diagnosis. A cohort of 432 women was assessed at 10-15th and 23-25th gestational weeks, 33-40 days and 180-195 days after delivery using the Edinburgh Postnatal Depression Scale (EPDS), Visual Analogue Scale (VAS), Hamilton Depression Rating Scale (HDRS), Montgomery-Åsberg Depression Rating Scale (MADRS), and Mini International Neuropsychiatric Interview (MINI). Spearman's rank correlation coefficient was used to assess agreement across instruments, and multivariable classification models were developed to predict the values of a binary scale using the other scales. Moderate agreement was shown between the EPDS and VAS and between the HDRS and MADRS throughout the perinatal period. However, agreement between the EPDS and HDRS decreased postpartum. A well-performing model for the estimation of current depression risk (EPDS > 9) was obtained with the VAS and MADRS, and a less robust one for the estimation of current major depressive episode (MDE) diagnosis (MINI) with the VAS and HDRS. When the EPDS is not feasible, the VAS may be used for rapid and comprehensive postpartum screening with reliability. However, a thorough structured interview or clinical examination remains necessary to diagnose a MDE.

Development of depression assessment tools using humanoid robots -Can tele-operated robots talk with depressive persons like humans?

BACKGROUND: Depression is a common mental disorder and causes significant social loss. Early intervention for depression is important. Nonetheless, depressed patients tend to conceal their symptoms from others based on shame and stigma, thus hesitate to visit psychiatrists especially during early phase. We hypothesize that application of humanoid robots would be a novel solution. Depressed patients may feel more comfortable talking with such robots than humans. METHODS: We recruited 13 patients with major depressive disorder (MDD) and 27 healthy volunteers as controls. Participants took both tele-operated humanoid robot and human interviews to evaluate severity of depression using the Hamilton Depression Rating Scale (HDRS). In addition, participants completed a self-administered questionnaire asking about their impressions of the robot interview. RESULTS: Confidence interval and t-test analysis have revealed that the HDRS scores are equally reliable between robot and human interviews. No significant differences were observed between the two interviews regarding "nervousness about the interview" and "hesitancy to talk about depressed moods and suicidal ideation." Compared to human interviews, robot interviews yielded significantly lower scores on shame-related factors especially among patients with MDD. LIMITATION: Small sample size, and the evaluator is male only. CONCLUSIONS: This is the first report to show the reliability of tele-operated humanoid robot interviews for assessment of depression. Robot interviews are potentially equally reliable as human interviews. Robot interviews are suggested to be more appropriate in assessing shame-related suppressed emotions and hidden thoughts of depressed patients in clinical practice, which may reduce the stigma associated with depression.

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

Comparison of Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale: Baked Straight From a Randomized Study.

BACKGROUND AND OBJECTIVES: The symptoms of major depressive disorder (MDD) are nowadays being assessed with the Hamilton and Montgomery-Åsberg Depression Rating Scales. However, there are few studies on the comparison of these two scales. Our study aimed to determine the correlation between the Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores at baseline through 12 weeks. METHODS: An ongoing randomized, open-label, three-arm study's interim analysis is portrayed here. The participants were assessed with HDRS and MADRS at baseline, four, eight, and 12 weeks after receiving oral tablets of either vilazodone (20-40 mg/d), escitalopram (10-20 mg/d), or vortioxetine (5-20 mg/d). This study is prospectively registered with the Clinical Trial Registry, India (CTRI/2022/07/043808). RESULTS: Of 71 recruited individuals, 49 (69%) completed the 12-week visit. At baseline, the three groups' median HDRS scores were 30.0, 29.5, and 29.0 (p=0.76), and at 12 weeks, they reduced to 19.5, 19.5, and 18.0 (p=0.18). At baseline, the group-wise median MADRS scores were 36, 36, and 36 (p=0.79); at 12 weeks, they were 24, 24, and 23 (p=0.03). The Pearson correlation revealed that the association between the changes in scores from baseline was strongest for escitalopram (r=0.70, p=0.002) followed by vortioxetine (r=0.59, p=0.01) and vilazodone (r=0.59, p=0.02). The Bland-Altman analysis showed that the mean difference between the scores was 5.11 (95% CI: 3.08-7.14). CONCLUSION: According to this interim study, HDRS and MADRS scores declined after 12 weeks of therapy. Both scores had strong positive correlation, and the difference between the scores reduced with time.

The HAM-D6 through the lens of grief: Clinical considerations for administering the six-item Hamilton Depression Rating Scale in the context of bereavement.

OBJECTIVES: Diagnosing mental health challenges in bereavement is controversial; however, regardless of one's position on this matter, assessments of bereaved individuals continue to occur in clinical and research contexts. It is critical for evaluations to account for contextual factors that are unique to bereavement. This paper summarizes considerations for diagnosing depression in bereaved individuals, focusing on use of the six-item Hamilton Depression Rating Scale (HAM-D6). METHODS: Following a literature review of the Hamilton Depression Rating Scale (HAM-D) and various versions, we summarized decision rules we used in scoring the HAM-D6 in a study of parents bereaved by cancer. We expanded on existing scoring guidelines for each of the HAM-D6 items, including depressed mood, work and activities, general somatic symptoms, guilt, psychic anxiety, and psychomotor retardation, and illustrated clinical distinctions and probes for assessors to consider through case examples from our research with bereaved parents. RESULTS: Considerations for assessing depressive symptoms and behavior changes in the context of bereavement were summarized. Symptoms that may be diagnostic of depression in some populations may reflect other factors in the bereaved, such as a change in priorities, social expectations surrounding grief, or avoidance of grief activators. Nuanced factors are important for assessors to consider when administering the HAM-D6 to bereaved individuals. SIGNIFICANCE OF RESULTS: Our sharing of these considerations is not intended to promote diagnosis of depression in bereavement but to highlight the unique contextual factors that distinguish symptoms of depression from common experiences of grievers when applying an assessment tool such as the HAM-D6. While validated measures can be constraining, they can have clinical utility; they may increase standardization in research, help clinicians communicate with each other, advance the field more generally to understand the varying struggles bereaved individuals experience, and systemically facilitate access to services via managed care.

Metabolic Effects of Antidepressants: Results of a Randomized Study's Interim Analysis.

BACKGROUND AND OBJECTIVES: Individuals with major depressive disorder exhibit a dysregulated metabolic profile. There are few studies on how vilazodone, escitalopram, and vortioxetine alter metabolic parameters. Our study aimed to determine the change in plasma glucose, HbA1c, serum cholesterol, triglyceride, and creatinine at 12 weeks. METHODS: An ongoing randomized, open-label, three-arm study's interim analysis is portrayed here. The participants were assessed at baseline, 4, 8, and 12 weeks after receiving oral tablets of either vilazodone (20-40mg/d), escitalopram (10-20mg/d), or vortioxetine (5-20mg/d). This study is CTRI-registered (2022/07/043808). RESULTS: Of 71 recruited participants, 49 (69%) completed the 12-week visit. The median Hamilton Depression Rating Scale (HDRS) scores of the participants in vilazodone, escitalopram, and vortioxetine groups were 30.0, 29.5, and 29.0 at baseline (p=0.76) and 19.5, 19.5, and 18.0 (p=0.18) at 12 weeks, respectively. The median fasting blood sugar (FBS) values were 98.5, 105.5, and 98.0 at baseline (p=0.07) and 94.0, 99.5, and 96.0 (p=0.19) at 12 weeks, for vilazodone, escitalopram, and vortioxetine groups, respectively. The post hoc analysis did not yield statistically significant differences regarding any parameters. CONCLUSION: According to this interim study, the HDRS scores declined after 12 weeks of therapy. The subjects' metabolic parameters did not significantly change. It is essential to perform further investigation regarding these impacts.

Association of depression with disease duration, quality of life and adherence in Parkinson's disease: A cross sectional study.

Background: Parkinson's disease (PD) is a progressive motor disorder often accompanied by non-motor symptoms such as depression. Objectives: The objective was to estimate the prevalence of depression in PD patients, and assess its association with disease duration, quality of life and adherence to treatment. Materials and Methods: This cross-sectional study was conducted in a tertiary care centre for patients diagnosed with PD. Depression was diagnosed using Hamilton Depression Rating Scale. The Chi-square test was used to assess the difference in proportions of depression in various types and severity of PD. Depression was also correlated with disease duration, quality of life (QOL) and adherence to treatment using the Pearson correlation test. A P value of <0.05 was considered statistically significant. Results: Among 51 patients, 20 (39.22%) patients were found to have depression. The mean duration of disease in depressed patients was significantly longer compared to that in non-depressed patients (7.99 ± 4.53 vs. 3.62 ± 2.23, P < 0.001), respectively. The non-depressed patients were better adherent to treatment (1.71 ± 1.5 vs. 0.56 ± 0.91). The quality of life of patients was significantly low for depressed patients (21.90 ± 6.91 vs. 13.16 ± 6.93, P < 0.001). Depression in Parkinson's patients was positively correlated with the duration of the disease (P-value <0.001); disease staging (P-value <0.001). Quality of life (QOL) had a strong correlation with depression (P-value <0.001) and Hoehn and Yahr (HY) staging (P-value <0.05). Conclusion: Depression was found in 39.22% of PD patients and was more significantly associated with disease duration, non-adherence to treatment and decreased quality of life.

Quality of Life and Medication Adherence in Patients With Major Depressive Disorder: An Interim Analysis of a Randomized Study.

BACKGROUND AND OBJECTIVES: Quality of life and medication adherence worsen in untreated depressed individuals. Studies examining how vilazodone, escitalopram, and vortioxetine affect these factors are few and far between. Our study's objectives were to determine the change in SF-36 at 12 weeks and the association between treatment outcome and medication adherence. METHODS: This is an interim analysis of a randomized, open-label, three-arm ongoing study. The participants were evaluated at baseline, four, eight, and 12 weeks after being randomly assigned to take either vilazodone (20-40 mg/d), escitalopram (10-20 mg/d), or vortioxetine (5-20 mg/d). This study is registered with CTRI, 2022/07/043808. RESULTS: Of 71 recruited participants, 49 (69%) completed the 12-week visit. The median scores of physical components of SF-36 for the three groups were 35.5, 35.0, and 35.0 at baseline (p=0.76) and 51.0, 49.5, and 53.0 (p<0.001) at 12 weeks respectively. Their corresponding median SF-36 scores for mental components were 43.0, 43.0, and 44.0 at baseline (p=0.34) and 66.0, 63.5, and 70.0 (p<0.001) at 12 weeks. The post hoc analysis yielded a significant difference (p<0.001) regarding SF-36 scores. MMAS-8 scores among the participants were similar (p=0.22) at 12 weeks. Higher medication adherence was associated with lesser depressive symptoms (r= -0.46, p=0.001). CONCLUSION: As per this interim analysis, vortioxetine substantially impacted the SF-36 scores, juxtaposed with vilazodone and escitalopram. The participants' clinical improvements were reflected by their adherence levels. These effects need to be probed further.

TMS-evoked potential in the dorsolateral prefrontal cortex to assess the severity of depression disease: a TMS-EEG study.

Objective: The combined use of transcranial magnetic stimulation and electroencephalography (TMS-EEG), as a powerful technique that can non-invasively probe the state of the brain, can be used as a method to study neurophysiological markers in the field of psychiatric disorders and discover potential diagnostic predictors. This study used TMS-evoked potentials (TEPs) to study the cortical activity of patients with major depressive disorder depression (MDD) and the correlation with clinical symptoms to provide an electrophysiological basis for the clinical diagnosis. Methods: A total of 41 patients and 42 healthy controls were recruited to study. Using TMS-EEG techniques to measure the left dorsolateral prefrontal cortex (DLPFC) 's TEP index and evaluate the clinical symptoms of MDD patients using the Hamilton Depression Scale-24 (HAMD-24). Results: MDD subjects performing TMS-EEG on the DLPFC showed lower cortical excitability P60 index levels than healthy controls. Further analysis revealed that the degree of P60 excitability within the DLPFC of MDD patients was significantly negatively correlated with the severity of depression. Conclusion: The low levels of P60 exhibited in DLPFC reflect low excitability in MDD; the P60 component can be used as a biomarker for MDD in clinical assessment tools.

An Interim Analysis of a Randomized, Open-Label Study of Vilazodone, Escitalopram, or Vortioxetine for Major Depressive Disorder.

INTRODUCTION: The troubling issues of conventional antidepressants are inadequate disease remission and potential adverse effects. There is a dearth of research findings comparing vilazodone, escitalopram, and vortioxetine. The objective of this analysis is to determinechanges in the Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) scoresand the incidence of adverse events at 12 weeks. METHODS: This is an exploratory interim analysis of a randomized, three-arm, open-label ongoing study. The participants were randomly assigned in a 1:1:1 ratio to receive either vilazodone (20-40 mg/d), escitalopram (10-20 mg/d), or vortioxetine (5-20 mg/d). Efficacy and safety assessments were done at baseline, four weeks, eight weeks, and 12 weeks. RESULTS: Forty-nine(69%) of the 71 enrolled participants (mean age 43.9±12.2 years; 37 men (52%)) completed the 12-week follow-up. At baseline, the three groups' median HDRS scores were 30.0, 29.5, and 29.0 (p=0.76), respectively, and at 12 weeks, they amounted to 19.5, 19.5, and 18.0 (p=0.18), respectively. At baseline, group-wise median MADRS scores were 36, 36, and 36, respectively (p=0.79); at 12 weeks, they were 24, 24, and 23, respectively (p=0.03). In the post-hoc analysis, the inter-group comparison of the change in HDRS (p = 0.02) and MADRS (p = 0.06) scores from baseline did not reach statistical significance. No participants experienced serious adverse events. CONCLUSION: In this initial assessment of a continuing study, vortioxetine exhibited a clinically (not statistically) significant drop in HDRS and MADRS scores, compared to vilazodone and escitalopram. The antidepressant effects need to be investigated further.

Efficacy and safety of selegiline for the treatment of Parkinson's disease: A systematic review and meta-analysis.

Background: Drug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time. Methods: PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes. Results: Among the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: -3.56 (-6.67, -0.45); 3 months: -3.32 (-3.75, -2.89); 6 months: -7.46 (-12.60, -2.32); 12 months: -5.07 (-6.74, -3.41); 48 months: -8.78 (-13.75, -3.80); 60 months: -11.06 (-16.19, -5.94)]. A similar trend was also found from the point estimates in UPDRS I, II, III, HAMD and WRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found. Conclusion: Selegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42021233145.

Comparative study of magnetic resonance imaging-based neuroimaging methods in older adults with depression.

BACKGROUND: Older patients with depression often have accompanying physical diseases, thus, their disease situation is more complex than that of younger people. The medical community has aimed for earlier diagnosis of senile depression due to ineffective treatment and eventual cognitive impairment. METHOD: Neuroimaging markers of senile depression were identified through the systematic analysis of multimodal data including resting-state functional MRI (rs-fMRI) and structural MRI (sMRI), and compared with clinical neural scales between older participants with and without depression. RESULTS: Morphological analysis of gray matter by MRI showed significantly enlarged volumes in the left inferior temporal gyrus and right talus fissure, and reduced volumes in the left parahippocampal gyrus and lentiform globus pallidus in the older depression group compared with those in the control group. Comparison of fractional amplitude of low-frequency fluctuation between the groups showed increased partial brain activity in the left posterior central gyrus and right anterior central gyrus in the depression group compared with those in the control group. CONCLUSION: Older patients with depression showed significant organic changes and significantly increased local brain activity. There was a positive correlation between the intensity of local brain activity in the superior occipital gyrus and the Hamilton Depression Rating Scale scores. GUIDING SIGNIFICANCE: It is important to assess the organic changes and the degree of brain activity in specific brain regions in the clinical diagnosis of depression in the older adults, to adjust treatment plans early according to the incidence.

Dimensions of the Hamilton Depression Rating Scale Correlate with Impulsivity and Personality Traits among Youth Patients with Depression.

The heterogeneity of symptoms in young patients with major depression disorder makes it difficult to properly identify and diagnose. Therefore, the appropriate evaluation of mood symptoms is important in early intervention. The aim of this study was to (a) establish dimensions of the Hamilton Depression Rating Scale (HDRS-17) in adolescents and young adults and (b) perform correlations between the identified dimensions and psychological variables (impulsivity, personality traits). This study enrolled 52 young patients with major depression disorder (MDD). The severity of the depressive symptoms was established using the HDRS-17. The factor structure of the scale was studied using the principal component analysis (PCA) with varimax rotation. The patients completed the self-reported Barratt Impulsiveness Scale (BIS-11) and Temperament and Character Inventory (TCI). The three dimensions of the HDRS-17 identified as core in adolescent and young patients with MDD were (1) psychic depression/motor retardation, (2) disturbed thinking, and (3) sleep disturbances/anxiety. In our study, dimension 1 correlated with reward dependence and cooperativeness; dimension 2 correlated with non-planning impulsivity, harm avoidance, and self-directedness; and dimension 3 correlated with reward dependence. Conclusions: Our study supports the previous findings, which indicate that a certain set of clinical features (including the HDRS-17 dimensions, not only total score) may represent a vulnerability pattern that characterizes patients with depression.

A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder.

BACKGROUND: Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD). METHODS: In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD17) total score. Secondary endpoints and safety were evaluated. RESULTS: Least-squares mean change in HAM-D17 total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%). LIMITATIONS: A short-term non-inferiority study without a placebo arm. CONCLUSIONS: This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.

Differential symptom cluster responses to repetitive transcranial magnetic stimulation treatment in depression.

Background: Repetitive transcranial magnetic stimulation (rTMS) can target specific neural circuits, which may allow for personalized treatment of depression. Treatment outcome is typically determined using sum scores from validated measurement scales; however, this may obscure differential improvements within distinct symptom domains. The objectives for this work were to determine: (1) whether a standard depression measure can be represented using a four symptom cluster model and (2) whether these symptom clusters had a differential response to rTMS treatment. Methods: Data were obtained from two multi-centre randomized controlled trials of rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC) for participants with treatment-resistant depression (TRD) conducted in Canada (THREE-D [Conducted between Sept 2013, and Oct 2016] and CARTBIND [Conducted between Apr 2016 and Feb 2018]). The first objective used confirmatory factor analytic techniques, and the second objective used a linear mixed effects model. Trial Registration: NCT01887782, NCT02729792. Findings: In the total sample of 596 participants with TRD, we found a model consisting of four symptom clusters adequately fit the data. The primary analysis using the THREE-D treatment trial found that symptom clusters demonstrated a differential response to rTMS treatment (F(3,5984) = 31.92, p < 0.001). The anxiety symptom cluster was significantly less responsive to treatment than other symptom clusters (t(6001) = -8.02, p < 0.001). These findings were replicated using data from the CARTBIND trial. Interpretation: There are distinct symptom clusters experienced by individuals with TRD that have a differential response to rTMS. Future work will determine whether differing rTMS treatment targets have distinct patterns of symptom cluster responses with the eventual goal of personalizing rTMS protocols based on an individual's clinical presentation. Funding: Canadian Institutes of Health Research, Brain Canada.