Effects of open-label transdermal nicotine antidepressant augmentation on affective symptoms and executive function in late-life depression.

BACKGROUND: Late-life depression (LLD) is characterized by a poor response to antidepressant medications and diminished cognitive performance, particularly in executive functioning. There is currently no accepted pharmacotherapy for LLD that effectively treats both mood and cognitive symptoms. This study investigated whether transdermal nicotine augmentation of standard antidepressant medications benefitted mood and cognitive symptoms in LLD. METHODS: Nonsmoking participants aged 60 years or older with unremitted LLD on stable SSRI or SNRI medications (N = 29) received transdermal nicotine patches up to a 21 mg daily dose over 12 weeks. Clinical measures assessed depression severity, secondary affective symptoms, and cognitive performance. Nicotine metabolite concentrations were obtained from blood samples. RESULTS: Depression severity significantly decreased over the trial, with a 76 % response rate and 59 % remission rate. Change in depression severity was positively associated with nicotine exposure. Participants also exhibited improvement in self-reported affective symptoms (apathy, insomnia, rumination, and generalized anxiety symptoms), negativity bias, and disability. Executive function test performance significantly improved, specifically in measures of cognitive control, as did subjective cognitive performance. Adverse events were generally mild, with 75 % of the sample tolerating the maximum dose. CONCLUSION: The current study extends our previous pilot open-label trial in LLD, supporting feasibility and tolerability of transdermal nicotine patches as antidepressant augmentation. Although preliminary, this open-label study supports the potential benefit of transdermal nicotine patches for both mood and cognitive symptoms of LLD. Further research, including definitive randomized, blinded trials, is warranted to confirm these findings and explore long-term risk and benefit. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT04433767).

Antidepressant prescription patterns and polypharmacy in outpatient psychiatry: a cross-sectional study.

Background and aim: Prescription patterns of antidepressants have changed over the years with a shift towards newer antidepressants with better tolerability and safety. Polypharmacy is common in psychiatry settings. The study aimed to evaluate the antidepressant drug prescription pattern and polypharmacy in a psychiatry outpatient setting. Investigations: This prospective observational study was conducted in a psychiatric outpatient clinic. The medication use data of eligible patients were collected. In addition, the rationale of antidepressant medication prescription, the defined daily dosage (DDD), the prescribed daily dose (PDD), and the PDD to DDD ratio were assessed. The assessment of prescription polypharmacy was conducted utilizing the framework provided by the National Association of State Mental Health Program Directors. Results: Data from 131 patients was analyzed. Major depressive disorder (32.8%) was the most common disorder for which antidepressants were prescribed. The majority, 91 (69.4%), received monotherapy. Selective serotonin reuptake inhibitors were the most frequently prescribed drugs in 69 (52.7%). Mirtazapine was the most frequently 32(24.4%) prescribed drug. Escitalopram and mirtazapine were the most commonly prescribed combination therapy (4.6%). Antipsychotic medications (37.4%) were the most widely co-prescribed medications, along with antidepressants. The PDD to DDD ratio was less than 1 for mirtazapine and imipramine; they were ≥1 for others. Psychiatric polypharmacy was documented in 87.1% of prescriptions. The total polypharmacy was not significantly (p>0.05) associated with demographic, illness, and treatment-related variables. Conclusion: Selective serotonin reuptake inhibitors were the most commonly prescribed antidepressants, monotherapy, and combination therapy. A substantial amount of patients received concomitant administration of antidepressants or psychotropic drugs, warranting careful monitoring.

Psychotropic medications and mortality from cardiovascular disease and suicide for individuals with depression in Taiwan.

BACKGROUND: Polypharmacy for treatment of depression has been increasing in Taiwan. METHODS: Individuals having depressive disorders were identified in a national database for healthcare services and followed up for 5 years. The mean dosage of antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics was calculated; the associations between the exposure dosage to different psychotropic medications and patients' overall death and death due to cardiovascular diseases (CVD) and suicide were examined. RESULTS: A total of 400,042 individuals with depressive disorders (63.8% women) were identified. Compared with those with no exposure to antidepressants, patients prescribed antidepressants had decreased mortality. Use of antipsychotics had a dose-related increase in overall mortality risk compared to no exposure group. Contrarily, depressed patients taking sedative-hypnotics had decreased overall and CVD mortality compared to no exposure group, with the most prominent decrease in CVD mortality of up to 54.9% for those in the moderate exposure group (hazard ratio: 0.451, 95% confidence interval: 0.405-0.503). A moderate or high dose of antidepressants or sedative-hypnotics was shown to be associated with a significantly increased mortality for suicide compared to those with no exposure. CONCLUSIONS: Antidepressant and sedative-hypnotic use was associated with decreased all-cause and CVD-related mortality and use of antipsychotics was associated with a dose-related increase in mortality risk. Future studies are needed to further clarify the involved mechanisms and benefits and risks should be carefully weighed when prescribing psychotropic medications in patients with depressive disorders.

Prescription Patterns and Predisposing Factors of Benzodiazepine and Z-Hypnotic Use During Pregnancy: A Nationwide Cohort Study.

PURPOSE: The use of benzodiazepines and Z-hypnotics during pregnancy has raised significant concerns in recent years. However, there are limited data that capture the prescription patterns and predisposing factors in use of these drugs, particularly among women who have been long-term users of benzodiazepines and Z-hypnotics before pregnancy. METHODS: This population-based cohort study comprised 2 930 988 pregnancies between 2004 and 2018 in Taiwan. Women who were dispensed benzodiazepines or Z-hypnotics during pregnancy were identified and further stratified into groups based on their status before pregnancy: long-term users (with a supply of more than 180 days within a year), short-term users (with a supply of less than 180 days within a year), and nonusers. Trends in the use of benzodiazepines or Z-hypnotics and concomitant use with antidepressants or opioids were assessed. Logistic regression models were utilized to identify factors associated with use of these drugs during pregnancy, and interrupted time series analyses (ITSA) were employed to evaluate utilization patterns of these drugs across different pregnancy-related periods. RESULTS: The overall prevalence of benzodiazepine and Z-hypnotic use was 3.5% during pregnancy. Among prepregnancy long-term users, an upward trend was observed. The concomitant use of antidepressants or opioids among exposed women increased threefold (from 8.6% to 23.1%) and sixfold (from 0.3% to 1.7%) from 2004 to 2018, respectively. Women with unhealthy lifestyle behaviors, such as alcohol abuse (OR 2.48; 95% CI, 2.02-3.03), drug abuse (OR 10.34; 95% CI, 8.46-12.64), and tobacco use (OR 2.19; 95% CI, 1.96-2.45), as well as those with psychiatric disorders like anxiety (OR 6.99; 95% CI, 6.77-7.22), insomnia (OR 15.99; 95% CI, 15.55-16.45), depression (OR 9.43; 95% CI, 9.07-9.80), and schizophrenia (OR 21.08; 95% CI, 18.76-23.69), and higher healthcare utilization, were more likely to use benzodiazepines or Z-hypnotics during pregnancy. ITSA revealed a sudden decrease in use of benzodiazepines and Z-hypnotics after recognition of pregnancy (level change -0.55 percentage point; 95% CI, -0.59 to -0.51). In contrast, exposures to benzodiazepines and Z-hypnotics increased significantly after delivery (level change 0.12 percentage point; 95% CI, 0.09 to 0.16). CONCLUSIONS: In this cohort study, an increased trend of benzodiazepine and Z-hypnotic use during pregnancy among prepregnancy long-term users, as well as concomitant use with antidepressants or opioids were found. The findings have highlighted the existence of various risk factors associated with the use of these drugs during pregnancy. Utilization patterns varied across different stages of pregnancy, highlighting the need for prescription guidelines and educational services for women using these drugs during pregnancy.

Developing an innovative 3D printing platform for production of personalised medicines in a hospital for the OPERA clinical trial.

Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.

Efficacy of ketamine versus esketamine in the treatment of perioperative depression: A review.

Depression is a significant factor contributing to postoperative occurrences, and patients diagnosed with depression have a higher risk for postoperative complications. Studies on cardiovascular surgery extensively addresses this concern. Several studies report that people who undergo coronary artery bypass graft surgery have a 20% chance of developing postoperative depression. A retrospective analysis of medical records spanning 21 years, involving 817 patients, revealed that approximately 40% of individuals undergoing coronary artery bypass grafting (CABG) were at risk of perioperative depression. Patients endure prolonged suffering from illness because each attempt with standard antidepressants requires several weeks to be effective. In addition, multi-drug combination adjuvants or combination medication therapy may alleviate symptoms for some individuals, but they also increase the risk of side effects. Conventional antidepressants primarily modulate the monoamine system, whereas different therapies target the serotonin, norepinephrine, and dopamine systems. Esketamine is a fast-acting antidepressant with high efficacy. Esketamine is the S-enantiomer of ketamine, a derivative of phencyclidine developed in 1956. Esketamine exerts its effect by targeting the glutaminergic system the glutaminergic system. In this paper, we discuss the current depression treatment strategies with a focus on the pharmacology and mechanism of action of esketamine. In addition, studies reporting use of esketamine to treat perioperative depressive symptoms are reviwed, and the potential future applications of the drug are presented.

Pentoxifylline as a Novel Add-on Therapy for Major Depressive Disorder in Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Evidence indicates an association between immune dysregulation and major depressive disorder (MDD). Pentoxifylline (PTX), a phosphodiesterase inhibitor, has been shown to reduce pro-inflammatory activities. The aim of this study was to evaluate changes in depressive symptoms and pro-inflammatory markers after administration of PTX as an adjunctive agent to citalopram in patients with MDD. METHODS: One hundred patients were randomly assigned to either citalopram (20 mg/day) plus placebo (twice daily) (n=50) or citalopram (20 mg/day) plus PTX (400 mg) (twice daily) (n=50). The Hamilton Depression Rating Scale-17 (HAM-D-17) scores at baseline, weeks 2, 4, 6, 8, 10, and 12 and serum levels of interleukin1-ß (IL-1-ß), tumor necrosis factor-α, C-reactive protein, IL-6, serotonin, IL-10, and brain-derived neurotrophic factor (BDNF) at baseline and week 12 were evaluated. RESULTS: HAM-D-17 score in the PTX group significantly reduced in comparison to the control group after weeks 4, 6, 8,10, and 12 ((LSMD): - 2.193, p=0.021; - 2.597, p=0.036; - 2.916, p=0.019; - 4.336, p=0.005; and - 4.087, p=0.008, respectively). Patients who received PTX had a better response (83%) and remission rate (79%) compared to the placebo group (49% and 40%, p=0.006 and p=0.01, respectively). Moreover, the reduction in serum concentrations of pro-inflammatory factors and increase in serotonin and BDNF in the PTX group was significantly greater than in the placebo group (p<0.001). CONCLUSION: These findings support the safety and efficacy of PTX as an adjunctive antidepressant agent with anti-inflammatory effects in patients with MDD.

Efficacy of addition of the anti-inflammatory, IV glutathione to standard ketamine IV therapy in major depressive disorder.

Ketamine, a N-methyl-D-aspartate (NMDA) antagonist, is used for treatment-resistant depression (TRD). Recent studies have shown that there are increased levels of pro-inflammatory cytokines in individuals with major depressive disorder (MDD) and those with higher levels of oxidative stress markers have a decreased or null response to conventional antidepressants. Glutathione (GSH) as an antioxidant adjuvant to ketamine has not been well studied. This double-blind study with 30 patients divided into 2 groups of 15 each, aimed to determine if GSH, added to standard ketamine infusion (GSH+K), rendered better outcomes in MDD patients versus patients receiving ketamine infusions with a normal saline placebo (K+NS). There were significant drops in BDI-II scores from day 1 to day 14, PHQ- scores from day 1 to day 14 and PHQ-9 scores day 14 to day 28, suggesting the overall treatment was effective. There were no statistically significant differences between the groups over time. However, a sustained improvement in depressive symptoms was observed for 14 days post-infusion in both groups.

Discovering the Potential Value of Coenzyme Q10 as an Adjuvant Treatment in Patients With Depression.

PURPOSE/BACKGROUND: Depressive disorder or mental cold is the most common mental disorder, and depression exists all over the world and in all countries and cultures. The results of several studies have shown that using compounds with antioxidant properties has been fruitful in patients with depression. Coenzyme Q10 (CoQ10) is a fat-soluble antioxidant and exerts its antioxidant effect by directly neutralizing free radicals or reducing tocopherol and preventing the inhibition of mitochondrial activity because of oxidative stress. This study aimed to investigate the effects of oral CoQ10 in patients with depression as an adjunctive treatment. METHODS/PROCEDURES: Sixty-nine patients with moderate and severe depression were randomly divided into 2 CoQ10 groups (36) and placebo (33). The first group of patients received CoQ10 supplements at a dose of 200 mg daily for 8 weeks along with standard interventions and treatments for depression, and the second group received standard treatments for depression along with a placebo. The change in the score of Montgomery-Åsberg Depression Rating Scale depression scale was evaluated 4 and 8 weeks after the intervention. Also, at baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity, total thiol groups, nitric oxide, malondialdehyde, and interleukin 6 were assessed. FINDINGS/RESULTS: The changes in the depression score at the end of the study showed that, in the group receiving the CoQ10 supplement after 8 weeks, there was a reduction in depression symptoms, which was statistically significant compared with before the start of the study Meanwhile, no significant changes were observed in the patients of the placebo group in terms of symptom reduction. Compared with baseline and the placebo condition, serum levels of nitric oxide and total thiol groups significantly decreased and increased, respectively. Also, no statistically significant changes were observed for interleukin 6, malondialdehyde, and total antioxidant capacity. IMPLICATIONS/CONCLUSIONS: A dose of 200 mg of CoQ10 supplement daily for 8 weeks can reduce depression and fatigue, as well as improve the quality of life of patients with depression. In addition, CoQ10 can significantly improve inflammation and oxidative stress status in patients with depression.

Suicide ideation and male-female differences in major depressive disorder.

OBJECTIVE: This study aimed to explore male-female differences in suicide ideation (SI) and suicide risk factors in major depressive disorder (MDD). METHODS: We analysed 482 adults (sample 1) and 438 elderly outpatients (sample 2) with MDD. Sample 1 was treated with different antidepressant combinations (escitalopram; bupropion plus escitalopram; venlafaxine plus mirtazapine) and assessed by means of the Concise Health Risk Tracking (SI), Quick Inventory of Depressive Symptomatology, Altman Mania Rating Scale and Psychiatric Diagnostic Screening Questionnaire. Sample 2 was treated with venlafaxine and assessed using the Hamilton scale for depression, Anxiety Sensitivity Index and Penn State Worry Questionnaire for anxiety, Beck Scale for Suicide Ideation and Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: In sample 1, females had greater depression severity (O.R 0.961 99%CI: 0.929 - 0.995), males reported more alcohol abuse (O.R 1.299 99%CI: 1.118 - 1.509) and active SI (O.R 1.109 99%CI: 1.005 - 1.255). In sample 2 men showed more severe SI (O.R 1.067; 99%CI: 1.014 - 1.122) and weight loss (OR = 5.89 99%CI: 1.01 - 34.19), women more gastrointestinal symptoms. CONCLUSIONS: In these selected samples, although women had more severe depression, men had more suicide risk factors. Such differences might contribute to men's increased suicide risk.

In major depressive disorder sex differences affect the clinical expression of depressive episodes. In comparison to men, women endorse higher levels of overall depression in adult MDD and more somatic anxiety and gastrointestinal symptoms in late-life MDD.After controlling for confounding variables, males have more severe SI and a larger number of suicide risk factors (eg. alcohol abuse; weight loss). The association between male sex and SI is detectable in both adults and elderly patients with MDD.Further studies are necessary to elucidate how sex differences in suicide ideation and suicide risk factors are related to men's increased suicide risk.

Effects of a single subanesthetic dose of esketamine on postoperative subthreshold depressive symptoms in patients undergoing unilateral modified radical mastectomy: a randomised, controlled, double-blind trial.

BACKGROUND: Breast cancer is the most common malignant tumor in females worldwide. During disease development, breast cancer patients suffer anxious and depressed, which may lead to worse quality of life or even higher mortality. Esketamine has been regarded as an antidepressant in breast cancer patients with mild or moderate depression. Here, we wonder whether the administration of esketamine could reduce the postoperative depressive symptom score of breast cancer patients who have no preoperative depression. METHODS: A total of 64 patients treated with unilateral modified radical mastectomy were randomly divided into an experimental group (esketamine group, Group E) and a control group (Group C), with 32 cases in each one. After anesthesia induction, Group C received 0.2 ml/kg of normal saline intravenously and Group E was administered 0.2 mg/kg intravenous esketamine. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores. The secondary outcomes included the Visual Analogue Scale (VAS) scores for pain, inflammatory markers, perioperative-related indicators, and the incidence of postoperative delirium, nausea and vomiting. RESULTS: The PHQ-9 score on postoperative day (POD) 1 in Group E declined from the preoperative level, while the score in Group C was higher than before, and the former was far lower than the latter (P = 0.047). There is no statistically significant difference in PHQ-9 scores between Group E and Group C on POD 3, 7, and 30. Moreover, the postoperative leukocyte level of Group E was higher than that of Group C, and the difference was statistically significant (P = 0.030). CONCLUSIONS: A single subanesthetic dose of esketamine can result in lower postoperative score on subthreshold depressive symptoms compared to the Group C on POD 1, without increasing the occurrence of postoperative adverse reactions. TRIAL REGISTRATION: Registration number: Chinese Clinical Trial Registry ChiCTR2200057028. Date of registration: 26/02/2022.

20(S)-Protopanaxadiol Exerts Antidepressive Effects in Chronic Corticosterone-Induced Rodent Animal Models as an Activator of Brain-Type Creatine Kinase.

20(S)-Protopanaxadiol (PPD) is one of the bioactive ingredients in ginseng and possesses neuroprotective properties. Brain-type creatine kinase (CK-BB) is an enzyme involved in brain energy homeostasis via the phosphocreatine-creatine kinase system. We previously identified PPD as directly bound to CK-BB and activated its activity in vitro. In this study, we explored the antidepressive effects of PPD that target CK-BB. First, we conducted time course studies on brain CK-BB, behaviors, and hippocampal structural plasticity responses to corticosterone (CORT) administration. Five weeks of CORT injection reduced CK-BB activity and protein levels and induced depression-like behaviors and hippocampal structural plasticity impairment. Next, a CK inhibitor and an adeno-associated virus-targeting CKB were used to diminish CK-BB activity or its expression in the brain. The loss of CK-BB in the brain led to depressive behaviors and morphological damage to spines in the hippocampus. Then, a polyclonal antibody against PPD was used to determine the distribution of PPD in the brain tissues. PPD was detected in the hippocampus and cortex and observed in astrocytes, neurons, and vascular endotheliocytes. Finally, different PPD doses were used in the chronic CORT-induced depression model. Treatment with a high dose of PPD significantly increased the activity and expression of CK-BB after long-term CORT injection. In addition, PPD alleviated the damage to depressive-like behaviors and structural plasticity induced by repeated CORT injection. Overall, our study revealed the critical role of CK-BB in mediating structural plasticity in CORT-induced depression and identified CK-BB as a therapeutic target for PPD, allowing us to treat stress-related mood disorders.

Enhanced neuronal survival and BDNF elevation via long-term co-activation of galanin 2 (GALR2) and neuropeptide Y1 receptors (NPY1R): potential therapeutic targets for major depressive disorder.

BACKGROUND: Major Depressive Disorder (MDD) is a prevalent and debilitating condition, necessitating novel therapeutic strategies due to the limited efficacy and adverse effects of current treatments. We explored how galanin receptor 2 (GALR2) and Neuropeptide Y1 Receptor (NPYY1R) agonists, working together, can boost brain cell growth and increase antidepressant-like effects in rats. This suggests new ways to treat Major Depressive Disorder (MDD). RESEARCH DESIGN AND METHODS: In a controlled laboratory setting, adult naive Sprague-Dawley rats were administered directly into the brain's ventricles, a method known as intracerebroventricular (ICV) administration, with GALR2 agonist (M1145), NPYY1R agonist, both, or in combination with a GALR2 antagonist (M871). Main outcome measures included long-term neuronal survival, differentiation, and behavioral. RESULTS: Co-administration of M1145 and NPYY1R agonist significantly enhanced neuronal survival and maturation in the ventral dentate gyrus, with a notable increase in Brain-Derived Neurotrophic Factor (BDNF) expression. This neurogenic effect was associated with an antidepressant-like effect, an outcome partially reversed by M871. CONCLUSIONS: GALR2 and NPYY1R agonists jointly promote hippocampal neurogenesis and exert antidepressant-like effects in rats without adverse outcomes, highlighting their therapeutic potential for MDD. The study's reliance on an animal model and intracerebroventricular delivery warrants further clinical exploration to confirm these promising results.

Characterization of rice endosperm-derived antidepressant-like peptide (REAP): An orally active novel tridecapeptide derived from rice protein.

It is ideal to ingest bioactive substances from daily foods to stay healthy. Rice is the staple food for almost half of the human population. We found that an orally administered enzymatic digest of rice endosperm protein exhibits antidepressant-like effects in the tail suspension test (TST) using mice. A comprehensive peptide analysis of the digest using liquid chromatography-tandem mass spectrometry was performed, and a tridecapeptide QQFLPEGQSQSQK, detected in the digest, was chemosynthesized. Oral administration of the tridecapeptide exhibited antidepressant-like effects at a low dose comparable to classical antidepressant in the TST. This also exhibited anti-depressant-like effect in the forced swim test. We named it rice endosperm-derived antidepressant-like peptide (REAP). Intriguingly, intraperitoneal administration had no effect. Orally administered REAP(8-13) but not REAP(1-7) exhibited antidepressant-like activity, suggesting that the C-terminal structure is important for the antidepressant-like effect. We confirmed the presence of REAP, corresponding to rice glutelin type B4(130-142) and B5(130-142), in the digest. The effects of REAP were blocked by both dopamine D1 and D2 antagonists. These results suggest that it exerts its antidepressant-like activity through activation of the dopamine system. Taken together, oral administration of a novel tridecapeptide exhibited antidepressant-like effects via the dopamine system. This is the first report of a rice-derived peptide that exhibits antidepressant-like effects.

Brain-Hazardous Medications and Potential Subadequate Antidepressant Dosing in Older Surgical Patients Receiving Home Antidepressants: An Observational Study of a Large US Health System.

BACKGROUND: Older surgical patients with depression often experience poor postoperative outcomes. Poor outcomes may stem from brain-hazardous medications and subadequate antidepressant dosing. METHODS: This was a retrospective, observational cohort study covering the period between January 1, 2021 and December 31, 2021. Patients ≥60 years of age who underwent inpatient surgery and had an overnight stay at an integrated academic health care system comprising 14 hospitals were eligible. We analyzed the prevalence of home central nervous system (CNS)-active potentially inappropriate medication (PIM) and potential subadequate antidepressant dosing in older surgical patients receiving home antidepressants. Univariable and multivariable regression models were used to identify factors associated with home CNS-active PIM prescribing and potential subadequate antidepressant dosing. Additionally, outcomes were compared among patients receiving and not receiving CNS-active PIMs and patients receiving and not receiving subadequate antidepressant dosing. RESULTS: A total of 8031 patients were included in this study (47% female, mean age = 70 years) of whom 2087 (26%) were prescribed antidepressants. Roughly one-half (49%, 95% confidence interval [CI], 46.5-50.1) of patients receiving home antidepressants were also receiving ≥1 CNS-active PIM and 29% (95% CI, 27.0-29.3) were receiving a potential subadequate dose. Factors associated with an increased likelihood of receiving a home CNS-active PIM included female sex (adjusted odds ratio [aOR], 1.46), anxiety (aOR, 2.43), asthma or chronic obstructive pulmonary disease (aOR, 1.39), and serotonin-norepinephrine reuptake inhibitor use (aOR, 1.54). Patients aged ≥75 years (aOR, 1.57), black race (aOR, 1.48) and those with congestive heart failure (aOR, 1.33) were more likely to be prescribed a potential subadequate antidepressant dose. Patients receiving potential subadequate antidepressant doses were discharged home less often (64% vs 73%), had a longer hospital length of stay (9 days vs 7 days), and a higher mortality rate (18% vs 10%) compared to patients receiving adequate home antidepressant doses (P-value for all <0.01). No differences in these outcomes were found among patients receiving home antidepressants with or without CNS-active PIMs. CONCLUSIONS: Older surgical patients receiving antidepressants are frequently prescribed brain-hazardous medications and potentially subadequate antidepressant doses. Those receiving subadequate antidepressant doses may be at risk for worse postoperative outcomes compared to patients receiving adequate doses. The role of preoperative medication optimization to improve outcomes for older surgical patients should be evaluated.

Análisis del conocimiento sobre los inhibidores selectivos de la recaptura de serotonina (ISRS) en el manejo de la depresión por médicos residentes y concurrentes de clínica médica de 5 hospitales de CABA / Review of the Knowledge on Selective Serotonin Reuptake Inhibitors (SSRIs) for Depression Management by Resident and Intern Physicians of the Medical Clinic of 5 Hospitals in CABA

Introducción: la depresión es un trastorno cada vez más prevalente alrededor del mundo. Los médicos generales son los profesionales de la salud más consultados por pacientes deprimidos. Más del 70% de los pacientes con depresión son vistos por médicos generales y no por especialistas en Psiquiatría. Según estudios realizados en Buenos Aires, más del 25% de los pacientes internados en Servicios de Clínica Médica en hospitales generales presenta depresión. Estos pacientes suelen ser atendidos y seguidos por médicos en formación, sean residentes o concurrentes de Clínica Médica. El objetivo del trabajo fue analizar el conocimiento sobre los inhibidores selectivos de la recaptura de serotonina (ISRS) que tienen los médicos residentes y concurrentes de Clínica Médica de 5 hospitales de la Ciudad Autónoma de Buenos Aires (CABA) y describir el tratamiento de un paciente depresivo por ellos. Material y métodos: se realizó un estudio descriptivo de corte transversal con un muestreo de tipo no probabilístico. Se utilizó como instrumento de medición un cuestionario semiestructurado organizado en dos secciones, una de datos demográficos que permiten caracterizar la muestra. La otra, de 15 ítems, explora los conocimientos sobre los ISRS y el tratamiento de la depresión. Dicho cuestionario fue revisado por 4 expertos. El instrumento es anónimo. Se aplicó a 59 médicos en formación en Clínica Médica, residentes y concurrentes, de 5 hospitales de la CABA, que participaron de forma voluntaria, durante el período agosto-septiembre de 2022. Resultados: la mayoría de los médicos en formación en Clínica Médica no tratan cuadros depresivos y, ante un paciente deprimido, solicitan la evaluación por un especialista en Salud Mental. Solo un 6,8% lo medica con un antidepresivo. Más del 75% de la muestra refiere recordar los conocimientos que tiene sobre de los ISRS de la cursada de Farmacología y un 13,6 de la cursada de Psiquiatría en la Facultad de Medicina. Conclusión: se observa un conocimiento deficitario sobre los ISRS en médicos residentes y concurrentes de Clínica Médica. Se considera necesario reforzar la formación sobre depresión y manejo de antidepresivos durante la residencia/concurrencia de Clínica Médica. (AU)

Introduction: depression is an increasingly common disorder around the world. General practitioners are the most frequently consulted health professionals by depressed patients. More than 70% of all depressed patients receive treatment by general practitioners and not by psychiatric specialists. According to studies conducted in Buenos Aires, more than 25% of all patients admitted to the Clinical Services in public hospitals present depression. These patients are usually under the care and follow-up of clinical trainee physicians, residents, or interns.This study aimed to analyze the knowledge about selective serotonin reuptake inhibitors (SSRIs) of clinical trainee residents and interns in five hospitals in the Ciudad Autónoma de Buenos Aires (CABA) and to describe their treatment of a depressive patient. Material and methods: we conducted a descriptive cross-sectional study with a non-probabilistic sampling. We used a semi-structured questionnaire arranged into two sections as a measuring tool. One, with demographic data to describe the sample. The other, with 15 items, explores respondents' knowledge of SSRIs and the treatment of depression. Four experts reviewed the questionnaire, which was anonymous. We applied it to 59 clinical medical trainees, residents, and interns from five CABA hospitals who volunteered to participate during August-September 2022. Results: most clinical trainees do not treat depressive conditions and, when confronted with a depressed patient, request an assessment by a Mental Health specialist. Only 6.8% medicate the patient with an antidepressant. More than 75% of the sample reported remembering their knowledge of SSRIs from the Pharmacology course and 13.6% from the Psychiatry course at the School of Medicine. Conclusion: there is a deficient knowledge about SSRIs in trainee residents and interns of Clínica Médica. We believe it is necessary to reinforce training on depression and management of antidepressants during residency/internship practice in Clínica Médica. (AU)

Diretrizes clínicas para tratamento da depressão: análise de fatores associados à qualidade e comparação de recomendações para pacientes não respondedores e com depressão resistente / Clinical guidelines for the treatment of depression: analysis of factors associated with quality and comparison of recommendations for nonresponding patients and for patients with resistant depression

Diretrizes clínicas (DCs) de alta qualidade são importantes para a assistência efetiva de pacientes com doenças crônicas, incluindo a depressão. A depressão é um dos principais problemas de saúde mundial, sendo um dos transtornos psiquiátricos mais comumente encontrados na prática médica, afetando cerca de 300 milhões de pessoas. Além de sua natureza debilitante e onerosa, muitas vezes pode levar a desfechos graves, tal como o suicídio, principalmente em pacientes que não respondem aos tratamentos. Assim, o objetivo geral desta tese foi identificar fatores das DCs associados à qualidade metodológica desses documentos e de suas recomendações, e comparar as recomendações para duas situações de falhas da farmacoterapia: pacientes não respondedores e pacientes com depressão resistente ao tratamento (DRT). Operacionalmente, foram feitas revisões sistemáticas da literatura em bases científicas e específicas de DCs, e incluídas DCs publicadas nos últimos onze anos que contivessem recomendações para o tratamento farmacológico de adultos com depressão. Para avaliação geral das DCs, foi aplicado o instrumento AGREE II, e para avaliação específica das recomendações, o instrumento AGREE-REX. As DCs foram consideradas de alta qualidade quando pontuaram com escores maiores ou iguais a 60% (no estudo descrito no capítulo 2) e maiores ou iguais a 80% (no estudo descrito no capítulo 3) no domínio 3 (Rigor de desenvolvimento) do AGREE II. As DCs com recomendações de alta qualidade foram as que pontuaram com mais de 60% no domínio 1 (Aplicabilidade Clínica) do AGREE-REX. Das 63 DCs selecionadas, 17 (27%) apresentaram alta qualidade, e 7 (11%) apresentaram recomendações de alta qualidade. Os fatores associados à maior qualidade foram gerenciamento de conflitos de interesses, equipe multiprofissional e tipo de instituição. A inclusão de representante do paciente na equipe também foi associada a recomendações de maior qualidade. Verificou-se que a maioria das DCs concorda com a necessidade de: reavaliar o diagnóstico, a presença de comorbidades, a adesão ao tratamento, ajustar a dosagem do antidepressivo e adicionar psicoterapia como os primeiros passos para aqueles que não respondem ao tratamento antidepressivo de primeira linha. Em relação às recomendações, há falhas importantes, incluindo a não apresentação de definição padronizada de resposta adequada/inadequada/parcial, e o não estabelecimento de tempo de tratamento necessário para declarar DRT. Todas as DCs incluíram a possibilidade de substituição do antidepressivo, potencialização com outros medicamentos e combinação de antidepressivos. Todavia, três DCs não recomendaram uma sequência entre eles. Por fim, verificou-se que das 17 DCs de alta qualidade e das 7 DCs com recomendações de alta qualidade, apenas duas incluíram definição e recomendações para DRT. Não existe consenso entre as DCs de alta qualidade quanto à definição e uso do termo DRT. Não foi possível extrair uma estratégia terapêutica convergente para DRT em adultos. Os resultados obtidos reforçam a necessidade de maior foco no aprimoramento da qualidade das DCs e de suas recomendações, especialmente nos subgrupos relativos à resposta inadequada ao tratamento e a DRT, nas quais as definições não são claras

High-quality clinical practice guidelines (CPGs) are important for treating patients with chronic diseases such as depression. Depression is a major health concern worldwide, affecting approximately 300 million people. It is one of the most prevalent psychiatric disorders in medical practice. It is not only debilitating and costly but can also lead to tragic consequences such as suicide, particularly in patients who do not respond to treatment. The objective of this thesis was to identify CPGs factors associated with the methodological quality of these documents and their recommendations. Furthermore, this thesis aimed to compare the recommendations in two pharmacotherapy failure situations: inadequate response to treatment and treatment-resistant depression (TRD). Systematic literature reviews were conducted on scientific and CPG-specific databases. Reviews were also conducted on CPGs published in the last eleven years that included recommendations for pharmacological treatment of adults with depression. The AGREE II instrument was used for the CPGs general assessment, while the AGREE-REX instrument was used specifically to assess their recommendations. CPGs were considered high quality if they achieved a score of at least 60% in the study mentioned in Chapter 2 and a score of at least 80% in the study mentioned in Chapter 3 in the AGREE II, rigour of development domain. The CPGs with high-quality recommendations were those that scored greater than 60% in Domain 1 (Clinical Applicability) of the AGREE-REX. Of the 63 selected CPGs, 17 (27%) were high quality, and 7 (11.1%) had recommendations of high quality. Factors associated with higher quality were conflict of interest management, multi-professional team, and type of institution. Inclusion of a patients representative on the team was associated with higher quality recommendations. Most CPGs agreed with the need to reassess diagnoses, comorbidities, and treatment adherence. They also agreed on adjusting antidepressant dosage and providing psychotherapy as a first step for patients who do not respond to first-line antidepressant treatment. There are significant shortcomings in the recommendations. In particular, the lack of a standardized definition of adequate, inadequate, or partial response to treatment and the lack of clarity surrounding the duration of treatment required to establish TRD. All CPGs included the possibility of antidepressant substitution, potentiation with other drugs, and a combination of antidepressants. However, three CPGs did not recommend a preferred sequence for these interventions. Finally, of the 17 high-quality CPGs and the 7 CPGs with high-quality recommendations, only two included definition and recommendations for TRD. There is no consensus among the high-quality CPGs regarding the definition and use of the term TRD. Ultimately, finding a convergent therapeutic strategy for TRD in adults was not possible. These results highlighted the need to focus more on improving the quality of CPGs and their recommendations, especially in the subgroups related to inadequate response to treatment and TRD, where definitions are unclear

S-ketamine as an adjuvant in patient-controlled intravenous analgesia for preventing postpartum depression: a randomized controlled trial.

BACKGROUND: Postpartum depression (PPD) is a common complication of cesarean section. S-ketamine given intravenously during surgery can help prevent PPD. However, whether S-ketamine in patient-controlled intravenous analgesia (PCIA) can reduce the incidence of PPD is unknown. This study assessed the effect of S-ketamine as an adjuvant in PCIA for preventing PPD in women undergoing cesarean delivery. METHODS: A total of 375 parturients scheduled to undergo cesarean section and then receive PCIA were recruited from a single center and were randomly assigned to control (C) group (sufentanil 2 µg/kg + tropisetron 10 mg) or S-ketamine (S) group (S-ketamine 0.5 mg/kg + sufentanil 2 µg/kg + tropisetron 10 mg). The primary outcome was the incidence of PPD measured by the Edinburgh postnatal depression scale (EPDS) after surgery. The secondary outcomes were EPDS scores, visual analog scale (VAS) scores, Ramsay sedation scale (RSS) scores, and the rate of adverse events, including headache, nausea, dizziness, drowsiness, and vomit. RESULTS: A total of 275 puerperal women were included in the study. The rate of depression in parturient on postoperative days 3, 14, 28 in the C group and S group were 17.6 and 8.2% (p < 0.05), 24.2 and 9.8% (p < 0.05), and 19.0 and 17.2% (p = 0.76) respectively. EPDS scores in the C group and S group on postoperative days 3,14, and 28 were 7.65 ± 3.14 and 6.00 ± 2.47 (p < 0.05), 7.62 ± 3.14 and 6.38 ± 2.67 (p < 0.05), and 7.35 ± 3.17 and 6.90 ± 2.78 (p = 0.15), respectively. The rate of adverse events in the C group and S group were headache 3.3 and 4.1% (p = 0.755), nausea 5.9 and 8.2% (p = 0.481), dizziness 9.2 and 12.3% (p = 0.434), drowsiness 6.5 and 10.7%(p = 0.274), and vomit 5.9 and 5.7% (p = 0.585). CONCLUSIONS: S-ketamine (0.01 mg/kg/h) as an adjuvant in PCIA significantly reduces the incidence of PPD within 14 days and relieves pain within 48 h after cesarean delivery, without increasing the rate of adverse reactions. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( ChiCTR2100050263 ) on August 24, 2021.

New Insights into Depressive Disorder with Respect to Low-Grade Inflammation and Fish Oil Intake.

Unipolar depression has been recognized as one of the major diseases by the World Health Organization in the 21st century. The etiology of depression is complicated and includes genetic factors, stress, aging, and special physical status (pregnancy, metabolic syndrome, and trauma). Numerous animal and human studies have demonstrated that n-3 polyunsaturated fatty acids (n-3 PUFAs) are highly correlated to cognition and depression. These nutritional antidepressants, including EPA and DHA, have a range of neurobiological activities contributing to their potential antidepressant effects. Our preclinical and clinical studies have indicated that n-3 PUFA supplementation in addition to standard antidepressant medications may provide synergistic neuroprotective and antioxidant/inflammatory effects. To translate our preliminary findings into clinical application, this paper reviews the existing evidence on the antidepressant effects of n-3 PUFAs and the potential underlying mechanisms, which include modulation of chronic lowgrade inflammation and the corresponding changes in peripheral blood immune biomarkers.

Resolvin E1 Attenuates Chronic Pain-Induced Depression-Like Behavior in Mice: Possible Involvement of Chemerin Receptor ChemR23.

The antidepressant effect of eicosapentaenoic acid-derived bioactive lipid, resolvin E1 (RvE1), was examined in a murine model of chronic pain-induced depression using a tail suspension test. Because RvE1 reportedly possesses agonistic activity on a chemerin receptor ChemR23, we also examined the antidepressant effect of chemerin. Two weeks after surgery for unilateral spared nerve injury to prepare neuropathic pain model mice, immobility time was measured in a tail suspension test. Chronic pain significantly increased immobility time, and this depression-like behavior was attenuated by intracerebroventricular injection of RvE1 (1 ng) or chemerin (500 ng). These results demonstrate that RvE1 exerts an antidepressant effect in a murine model of chronic pain-induced depression, which is likely to be via ChemR23. RvE1 and its receptor may be promising targets to develop novel antidepressants.