Background: Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the analgesic effect and safety ...of duloxetine in total knee arthroplasty (TKA). Methods: A systematic search was completed on MEDLINE, PsycINFO, and Embase from inception to December 2022 to find relevant articles. We used Cochrane methodology to evaluate the bias of included studies. Investigated outcomes included postoperative pain, opioid consumption, adverse events (AEs), range of motion (ROM), emotional and physical function, patient satisfaction, patient-controlled analgesia (PCA), knee-specific outcomes, wound complications, skin temperature, inflammatory markers, length of stay, and incidence of manipulations. Results: Nine articles involving 942 participants were included in our systematic review. Out of nine papers, eight were randomized clinical trials and one was a retrospective study. The results of these studies indicated the analgesic effect of duloxetine on postoperative pain, which was measured using numeric rating scale and visual analogue scale. Deluxetine was also effective in reducing the morphine requirement and wound complications and enhancing patient satisfaction after surgery. However, the results on ROM, PCA, and knee-specific outcomes were contraventional. Deluxetine was generally safe without serious AEs. The most common AEs included headache, nausea, vomiting, dry mouth, and constipation. Conclusion: Duloxetine may be an effective treatment option for postoperative pain following TKA, but further rigorously designed and well-controlled randomized trials are required.
Over the past two decades, ketamine has emerged as a novel effective and rapid-acting antidepressant. While the vast majority of studies on ketamine have focused on its ability to reduce the severity ...of depression broadly, its effectiveness in specific domains such as cognition, anhedonia, suicidality, and workplace/social/scholastic functionality has been neglected. Similarly, current treatments (e.g., SSRIs and SNRIs) aim to improve overall depression severity, which often results in the persistence of one or more residual symptom domains and prevents full recovery to premorbid functionality. In this review, we narratively synthesize the literature pertaining to the effectiveness of ketamine in treating key domains of depressive symptomatology (i.e., cognition, anhedonia, suicidality, and psychosocial functionality). Our findings suggest that ketamine is effective across domains varyingly, with the strongest evidence being for its ability to reduce suicidality. The rapid acting nature of ketamine further supports its use in treating suicidality and potentially preventing the completion of suicide. Evidence for the effectiveness of ketamine in other domains is weak, primarily due to a lack of robust studies specifically designed to assess these domains as primary outcomes. Future studies should scrutinize the effects of ketamine on specific domains of depression to optimize its implementation.
This article is part of the Special Issue on 'Ketamine and its Metabolites'.
•Ketamine and its enantiomers are an effective antidepressant modality with varying effectiveness across key domains of depression (i.e., suicidality, psychosocial functionality, cognition and anhedonia).•The strongest evidence was shown for reducing suicidality rapidly.•The evidence for efficacy of ketamine on ameliorating domains of cognition, psychosocial functioning and anhedonia is weak due to lack of studies mainly studying foregoing domains as primary outcomes.•Future researchers should design robust trials to further the therapeutic role of ketamine and its enantiomers in treating disparate domains of depression.
Background:
Ketamine is an emerging treatment for treatment-resistant depression (TRD) associated with rapid and robust improvements in depressive symptoms and suicidality. However, the efficacy and ...safety of ketamine in transitional age youth (TAY; age 18–25) populations remains understudied.
Methods:
In this retrospective analysis, TAY patients (n = 52) receiving ketamine for TRD were matched for sex, primary diagnosis, baseline depression severity, and treatment resistance with a general adult (GA) sample (age 30–60). Patients received four ketamine infusions over 2 weeks (0.5–0.75 mg/kg over 40 min). The primary outcome was the change in Quick Inventory of Depressive Symptomatology Self-Report 16-item (QIDS-SR16) over time. Secondary outcomes were changes in QIDS-SR16 suicidal ideation (SI) item, anxiety (Generalized Anxiety Disorder 7-item (GAD-7)), and adverse effects (ClinicalTrials.gov: NCT04209296).
Results:
A significant main effect of infusions on reduction of total QIDS-SR16 (p < 0.001), QIDS-SR16 SI (p < 0.001), and GAD-7 (p < 0.001) scores was observed in the TAY group with moderate effect sizes, indicative of clinically significant improvements in depression, anxiety, and suicidality. There were no significant differences between TAY and GA groups on these measures over time, suggesting comparable improvements in both groups. Safety and tolerability outcomes were comparable between groups with only mild, transient adverse effects observed.
Conclusion:
Ketamine was associated with comparable clinical benefits, safety, and tolerability in a TAY sample as compared to a matched GA TRD sample.
The 2019 novel coronavirus pandemic, severe acute respiratory syndrome CoV-2 (COVID-19), has been a worldwide urgent public health threat, resulting in six-hundred seventy thousand deaths to date. ...The COVID-19 pandemic has led to a series of public health challenges. One such challenge is the management of diseases such as chronic neurological diseases during an epidemic event. COVID-19 affects all kinds of people, including older people with chronic underlying diseases, who are particularly at risk of severe infection or even death. Chronic neurological diseases such as epilepsy, dementia, Parkinson’s disease (PD), and multiple sclerosis (MS) are frequently associated with comorbidities; thus, these patients are in the high-risk category. Therefore, in this article, we review associations and challenges the people with epilepsy, dementia, PD, and MS faces during the COVID-19 pandemic and suggest approaches to provide consensus recommendations on how to provide the best possible care.
Psychiatric and metabolic disorders are highly comorbid and the relationship between these disorders is bidirectional. The mechanisms underlying the association between psychiatric and metabolic ...disorders are presently unclear, which warrants investigation into the dynamics of the interplay between metabolism, substrate utilization, and energy expenditure in psychiatric populations, and how these constructs compare to those in healthy controls. Indirect calorimetry (IC) methods are a reliable, minimally invasive means for assessing metabolic rate and substrate utilization in humans. This review synthesizes the extant literature on the use of IC on resting metabolism in psychiatric populations to investigate the interaction between psychiatric and metabolic functioning. Consistently, resting energy expenditures and/or substrate utilization values were significantly different between psychiatric and healthy populations in the studies contained in this review. Furthermore, resting energy expenditure values were systematically overestimated when derived from predictive equations, compared to when measured by IC, in psychiatric populations. High heterogeneity between study populations (e.g., differing diagnoses and drug regimens) and methodologies (e.g., differing posture, time of day, and fasting status at measurement) impeded the synthesis of results. Standardized IC protocols would benefit this line of research by enabling meta-analyses, revealing trends within and between different psychiatric disorders.
This cross-sectional study is aimed at assessing the effects of opium use disorder (OUD) on attention, working memory, and information-processing speed. Thirty outpatients with OUD and 20 healthy ...controls (HCs) were assessed using a neuropsychological battery consisted of Auditory Verbal Learning Test-Revised (AVLT-R), Brief Visuospatial Memory Test-Revised (BVMT-R), Digit Forward and Backward Tests (DFT and DBT), and WAIS-R Digit Symbol Substitution Test (DSST). The most affected cognitive functions in patients with OUD were detected by DBT and DSST. However, we found no significant difference between patients according to the route of administration. Within patients with OUD, DBT score was associated with opium use quantity (OUQ) (r=−0.385), and DBT (r=0.483) and DSST (r=0.542) scores were correlated with duration of use. Our findings indicated that working memory and information-processing speed are the most affected domains of cognitive functioning. DBT and DSST could be used as brief assessments in clinical settings to screen for cognitive deficits in patients with OUD.
Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive ...impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI.
This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5-20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint.
Our findings showed significant effects for time (χ
= 7.771, p = 0.005), treatment (χ
= 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ
= 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047).
Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo.
NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).
Depression and obesity are highly comorbid conditions with shared biological mechanisms. It remains unclear how depressive symptoms and body mass index (BMI) interact in relation to inflammation. ...This cross-sectional study investigated the independent associations of depressive symptoms and BMI with high sensitivity C-reactive protein (hs-CRP), as well as the moderating role of BMI on the depressive symptoms-hs-CRP association.
Participants (n = 8827) from the 2015–2018 National Health and Nutrition Examination Surveys were aged ≥20 with a BMI ≥18.5 kg/m2, completed the Depression Screener, and had hs-CRP data. Multivariable linear regression was used to analyze hs-CRP in relation to depressive symptoms and BMI. An interaction term was included to examine whether the depressive symptoms-hs-CRP relationship differs depending on BMI.
There was a slight, albeit non-significant, increase in hs-CRP levels with each one-point increase in depressive symptoms (aCoef.Estm. = 0.01, 95% CI = −0.05, 0.06, p = 0.754). Participants with overweight (aCoef.Estm. = 1.07, 95% CI = 0.61, 1.53, p < 0.001) or obese (aCoef.Estm. = 3.51, 95% CI = 3.04, 3.98, p < 0.001) BMIs had higher mean hs-CRP levels than those with a healthy BMI. There were no significant interactions between depressive symptoms and overweight (aCoef.Estm. = 0.04, 95% CI = −0.04, 0.13, p = 0.278) or obese (aCoef.Estm. = 0.11, 95% CI = −0.01, 0.22, p = 0.066) BMI indicating a lack of difference in the depressive symptoms-hs-CRP association across participants in the healthy versus overweight and obese ranges.
This study suggests that BMI might not act as a moderator in the association between depressive symptoms and hs-CRP. Results should be replicated in larger samples. Further research is warranted to understand underlying mechanisms.
•Depression and obesity share biological mechanisms.•It is unclear how depressive symptoms and BMI interact in relation to inflammation.•This study investigated if BMI moderates the depressive symptoms-hs-CRP association.•The depressive symptoms-hs-CRP association did not differ by BMI.•Further research is warranted to understand underlying mechanisms.
Findings from another study showed that women with depression who had never used antidepressants had reduced odds of having an obese BMI.9 Moreover, the positive relationship between antidepressant ...use and an obese BMI only became significant when analyses were limited to those with a history of depression.9 A large, population-level analysis is warranted to clarify the associations between depression, antidepressant use and BMI. Exposure variables Participants self-reported the frequency of their depressive symptoms over the past 2 weeks in response to items DPQ010 through DPQ090, the nine questions of the Patient Health Questionnaire-9 (PHQ-9).10 The PHQ-9 is a reliable and valid measure of depression, aligned with the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition.10 Each symptom was scored on a 4-point scale ranging from 0 (not experienced) to 3 (experienced nearly every day). Potential covariates (ie, age, sex, race, poverty–income ratio, education, cigarette smoking status, alcohol use and minutes of sedentary activity per day) were selected based on prior work.9 Age was definitively included in the model.9 Univariate feature selection was then used to determine which of the remaining potential covariates were to be included in the final model if p<0.10. Table 1 Demographic characteristics of the study population (n=27 990) Characteristic Depression—yes Depression—no Statistic P value Sample size 2405 25 585 Age*, mean (SD) 47.06 (16.05) 47.90 (16.97) −1.68 0.097 Sex—female (%) 63.16 48.87 156.81 <0.001 Race (%) 53.08 <0.001 Mexican American 8.47 8.54 Other Hispanic 8.62 5.59 Non-Hispanic white 61.68 67.51 Non-Hispanic black 13.51 10.79 Other race—including multiracial 7.72 7.57 Education—≤high school (%) 52.73 37.24 194.54 <0.001 Cigarette smoking—yes (%) 39.06 17.73 560.95 <0.001 Alcohol use—yes (%) 62.80 70.16 49.04 <0.001 Minutes sedentary activity/day*, mean (SD) 387.53 (222.58) 370.43 (200.88) 2.33 0.021 PHQ-9*, mean (SD) 13.94 (3.72) 2.08 (2.37) 133.76 <0.001 Antidepressant use—yes (%)† 32.02 10.20 877.00 <0.001 SSRI 58.32 60.87 12.26 0.477 SNRI 17.63 16.03 8.49 0.476 TCA 5.79 7.42 18.05 0.351 MAOI 0.00 0.19 10.92 0.501 Atypical 18.26 15.49 25.57 0.188 Unspecified 0.00 0.01 0.18 0.656 BMI (%) 104.64 <0.001 Normal 25.21 28.59 Overweight 26.31 34.07 Obese 48.48 37.34 Categorical characteristics reported as weighted per cent; continuous characteristics reported as weighted mean (SD). χ2 statistics values are given. *Denotes t-test statistics values. †Antidepressant class subsets presented as weighted percent of total antidepressant users.
PDF
