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Micronutrient deficiencies and excesses are closely related to developing and treating depression. Traditional and effective antidepressants include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and lithium. There is no consensus on the fluctuation of zinc (Zn 2+ ), magnesium (Mg 2+ ), calcium (Ca 2+ ), copper (Cu 2+ ), iron (Fe 2+ ), and manganese (Mn 2+ ) ion levels in depressed individuals before and after therapy. In order to determine whether there were changes in blood and cerebrospinal fluid (CSF) levels of these ions in depressed patients compared with healthy controls and depressed patients treated with TCAs, SSRIs, or lithium, we applied a systematic review and meta-analysis. Using the Stata 17.0 software, we performed a systematic review and meta-analysis of the changes in ion levels in human samples from healthy controls, depressive patients, and patients treated with TCAs, SSRIs, and lithium, respectively. By searching the PubMed, EMBASE, Google Scholar, Web of Science, China National Knowledge Infrastructure (CNKI), and WAN FANG databases, 75 published analyzable papers were chosen. In the blood, the levels of Zn 2+ and Mg 2+ in depressed patients had decreased while the Ca 2+ and Cu 2+ levels had increased compared to healthy controls, Fe 2+ and Mn 2+ levels have not significantly changed. After treatment with SSRIs, the levels of Zn 2+ and Ca 2+ in depressed patients increased while Cu 2+ levels decreased. Mg 2+ and Ca 2+ levels were increased in depressed patients after Lithium treatment. The findings of the meta-analysis revealed that micronutrient levels were closely associated with the onset of depression and prompted more research into the underlying mechanisms as well as the pathophysiological and therapeutic implications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To examine the association between depression, the use of antidepressants, and atherosclerotic cardiovascular disease (ASCVD)., Methods: The South Korean national claims data was used. Among a nationally representative population, 273,656 subjects who had been diagnosed with depression and prescribed antidepressants ("DEP with antidepressants") and 78,851 subjects who had been diagnosed with depression but not prescribed antidepressants ("DEP without antidepressants") were identified to be eligible. Healthy controls (HCs) were 1:1 matched with DEP with antidepressants group for age and sex. We followed up on the occurrence of ASCVD including ischemic heart diseases and ischemic stroke., Results: The risk of ASCVD was increased in the DEP with antidepressants group and decreased in the DEP without antidepressants group compared to HCs. Among those under antidepressants, tricyclic antidepressant users showed the highest risk of ASCVD compared to HCs. Among young adults, the risk of ASCVD was increased in both groups., Conclusion: The risk of ASCVD increased in depression patients taking antidepressants, while it decreased in depression patients not taking antidepressants. However, the relationship showed differences according to drug class and age group., Competing Interests: Declaration of competing interest Jungkuk Lee and Dongwoo Kang were employed by Hanmi Pharm. Co. and the remaining authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Continuous use of antidepressants can relieve depressive symptoms and prevent recurrence in people with depression; however, many studies have reported low drug compliance rates. This study aimed to investigate the relationship between the type of initial antidepressants and treatment adherence in outpatients with new onset depression., Methods: This was a retrospective cohort study using National Health Insurance claim data for services provided in 2012. We examined data from 142,336 individuals aged 18 years or older, who were continuously enrolled in treatment after a new episode of depression, and had initiated antidepressant treatment. A new diagnosis of depression, is defined as a first reported diagnosis of depression in the preceding five years. Adherence was operationally defined as the antidepressant being dispensed to the patient at least 80% of the time during the first three- and six-month treatment periods. To investigate the relationship between the initial type of antidepressants and treatment adherence, we estimated adjusted odds ratios and 95% confidence intervals using logistic regression analysis, adjusting for socio-demographic and health care utilization characteristics., Results: A statistically significant association was found between initial antidepressant type and adherence in the first three- and six-month treatment periods for employed and self-employed patients newly diagnosed with major depression. In addition, patients with starting prescriptions for tricyclic antidepressants had significantly lower adherence compared to selective serotonin reuptake inhibitors., Limitations: This study used national insurance data; therefore, only variables on the claim form were available, and psychological and environmental factors were not considered., Conclusions: This was the first study to demonstrate the relationship between initial antidepressant type and treatment adherence among Korean outpatients with new onset depression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Tricyclic antidepressants (TCA) continue to be an important group of drugs, but it is unclear whether a dose-response relationship is supported by high-level evidence., Methods: Systematic review in the Cochrane Collaboration's Central Register of Controlled Trials (CENTRAL) of studies randomizing patients to at least two doses of one TCA, complemented by searches in Medline, Embase, and PsycInfo. In multilevel regression, we calculated the standardized mean difference (SMD) in antidepressant efficacy per mg TCA dose increase, and we analyzed drop-outs due to adverse events. Finally, we computed random effects meta-analyses of all dose comparisons investigated in a minimum of two studies., Results: Out of 5365 studies screened, we included 15 randomized trials on 24 comparisons of 14 different dose contrasts. We found a statistically non-significant positive effect of increasing the dose: 0.34 SMD with 100 mg/d dose increase ([-0.03; 0.70] p = 0.073). While several comparisons showed no clear signal of a dose gradient, 300 mg of imipramine/desipramine is statistically significantly superior to 150 mg (SMD: 0.80 [0.28; 1.33], p = 0.003, I 2 : 0%). Drop-outs increased with higher doses, albeit not statistically significantly: Odds ratio (OR) of 1.44 with 100 mg dose increase [0.54; 3.86]. Overall, risk of bias was high., Limitations: Limited number of studies with mainly high risk of bias., Conclusions: So far, data on a dose-response relationship in TCAs from direct dose comparisons are inconclusive. Clinically, escalation to high doses may be justified if side effects are bearable., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available., Methods: In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3h daily for 10days (blood alcohol concentration ∼150mg%) followed by daily injection of 10mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand., Results: Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains., Conclusions: The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to investigate characteristics, drug use patterns, and predictors for treatment choice in older German patients initiating antidepressant (AD) treatment., Methods: Using the German Pharmacoepidemiological Research Database, we identified a cohort of AD initiators aged at least 65 years between 2005 and 2011. Potential indications, co-morbidity, and co-medication as well as treatment patterns such as the duration of the first treatment episode were assessed. In addition, a logistic regression model was used to identify independent predictors for initiating treatment with tricyclic ADs (TCAs) compared to selective serotonin reuptake inhibitors (SSRIs)., Results: Overall, 508,810 individuals were included in the cohort. About 55 % of patients initiated AD treatment with TCAs, followed by 22 % receiving SSRIs. During the study period, a decrease of treatment initiation with TCAs was observed. Higher age and male sex as well as being diagnosed with depression were highly associated with SSRI treatment, whereas pain and sleeping disorders were strong predictors for initiating TCA treatment. The duration of the first treatment episode was substantially longer in SSRI users compared to TCA initiators (median 119 vs. 43 days)., Conclusions: Potential indications and drug use patterns in older German AD initiators varied substantially for different drug classes and single agents. Given the anticholinergic and sedative properties of TCAs, the frequent use of this drug class though probably related to indications such as pain was remarkable.

The efficacy of modern antidepressants is largely related to their ability to enhance neurotransmission of serotonin. The medicines with serotonergic properties include trazodone, which is intermediate between tricyclic antidepressants with their powerful antidepressive effect and selective serotonin reuptake inhibitors, as first-line agents in the treatment of depression and anxiety disorders. The value of trazodone for clinical practice is determined by the effective elimination of the symptoms of major depressive disorder in combination with good tolerability, including in elderly patients. Among the advantages of trazodone is the absence of such undesirable effects as sexual dysfunction and weight gain. Trazodone has significant hypnotic and anxiolytic properties, which gives it special meaning in the treatment of depression, combined with insomnia and anxiety. It is emphasized that the beneficial effect of trazodone on sleep should not prevent its main use as a drug for treating major depressive disorder regardless of whether depression is accompanied by insomnia or not.

In this study we have generated a pharmacophore model of triple uptake inhibitor compounds based on novel asymmetric pyran derivatives and the newly developed asymmetric furan derivatives. The model revealed features important for inhibitors to exhibit a balanced activity against dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET). In particular, a 'folded' conformation was found common to the active pyran compounds in the training set and was crucial to triple uptake inhibitory activity. Furthermore, the distances between the benzhydryl moiety and the N-benzyl group as well as the orientation of the secondary nitrogen were also important for TUI activity. We have validated our findings by synthesizing and testing novel asymmetric pyran analogs. The present work has also resulted in the discovery of a new series of asymmetric tetrahydrofuran derivatives as novel TUIs. Lead compounds 41 and 42 exhibited moderate TUI activity. Interestingly, the highest TUI activity by lead tetrahydrofuran compounds for example, 41 and 42, was exhibited in a stereochemical preference similar to pyran TUI for example, D-161., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Depression is a common psychiatric comorbidity in Parkinson's disease (PD) and contributes to significant impairments in cognitive, functional, motor, and social performance. This results in reduced quality of life, higher levels of care dependency, and increased caregiver burden. When treating depression, it is important to ensure that the patient's response to treatment will be adequately monitored. This can be accomplished in neurology or primary care settings, or in clinical settings with interdisciplinary treatment teams. Mental health services should be engaged early as a component of ongoing comprehensive care. This article reviews a general approach to treating the pharmacotherapy of depression in PD. Ultimately, clinicians should rely on empiric assessments of known risks and putative benefits to guide treatment decisions and should include a targeted and individualized multimodal approach that utilizes psychotherapeutic interventions along with pharmacologic therapies., (© 2013 Pharmacotherapy Publications, Inc.)

This article explores the clinical implications of withdrawal syndromes associated with antidepressant drugs. The author shares their own clinical observations and proposes an oppositional model of tolerance to explain the loss of treatment effectiveness and the occurrence of side effects over time. The article also discusses the phenomenon of withdrawal syndromes during the tapering and discontinuation of antidepressants, emphasizing the need for personalized approaches and the potential for severe and persistent symptoms. The author suggests the use of clonazepam, a medication with neuroprotective properties, to support patients during this phase, and highlights the importance of self-therapy and psychotherapeutic strategies in the discontinuation process. The author calls for further research on the behavioral toxicity of antidepressant medications and emphasizes the importance of individualized treatment approaches. [Extracted from the article]

Introduction: Chronic pain (CP) and depression/anxiety often coexist, worsening each other's symptoms. Treating this comorbidity is challenging. Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are the first-line treatment options for this comorbidity, although sometimes they are not effective and/or well tolerated by patients, and there is little clinical evidence that selective serotonin reuptake inhibitors are useful for controlling CP. The antidepressant vortioxetine, with a multimodal mechanism that may help reduce pain, has proven clinical efficacy in patients with major depressive disorder (MDD). This study investigated vortioxetine's effectiveness for MDD and CP in clinical practice. Methods: This was a 3-month, multicenter, prospective, open-label, non-interventional pharmacoepidemiologic study. Patients (n = 64) with MDD (9-item Patient Health Questionnaire [PHQ-9] score ≥ 15) and CP (visual analogue scale [VAS] score ≥ 4) were treated with vortioxetine for 3 months (initiated with 10 mg/day, with flexible dosing thereafter [5–20 mg/day]). VAS, Clinical Global Impression (CGI), and Patient Global Impression (PGI) scales were used at baseline and at 1 and 3 months. Brief Pain Inventory (BPI), PHQ-9 scale, and Satisfaction with Medicines Questionnaire (SATMED-Q) were used at baseline and at 3 months. Adverse Events (AEs) were recorded. Descriptive statistics, chi-square tests, and Student's t-tests were used for paired data. Results: MDD patients showed a statistically significant improvement in VAS from baseline (mean [standard deviation (SD)]: 7.42 [0.69]) to 1 month (mean [SD]: 6.1 [0.81], P < 0.001) and 3 months (mean [SD]: 5.09 [1.26], P < 0.0001). Similarly, BPI and PHQ-9 scores showed significant improvement from baseline (mean [SD]: 6.20 [0.80] and 16.63 [1.47], respectively) to 3 months (mean [SD]: 4.73 [0.98] and 7.30 [2.60], P < 0.0001, respectively). Patients showed clinical improvement with CGI and PGI scales and reported being satisfied with the treatment in the SATMED-Q. A few mild EAs were registered. Conclusion: Vortioxetine can relieve depressive and pain symptoms, with a good safety profile, in patients with MDD and CP. [ABSTRACT FROM AUTHOR]

Depression is not similar to daily mood fluctuations and temporary emotional responses to day‐to‐day activities. Depression is not a passing problem; it is an ongoing problem. It deals with different episodes consisting of several symptoms that last for at least 2 weeks. It can be seen for several weeks, months, or years. At its final stage, or can say, in its worst condition, it can lead to suicide. Antidepressants are used to inhibit the reuptake of the neurotransmitters by some selective receptors, which increase the concentration of specific neurotransmitters around the nerves in the brain. Drugs that are currently being used for the management of various types of depression include selective serotonin reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, serotonin, noradrenaline reuptake inhibitors, etc. In this review, we have outlined different symptoms, causes, and recent advancements in nitrogen‐containing heterocyclic drug candidates for the management of depression. This article highlights the various structural features along with the structure–activity relationship (SAR) of nitrogen‐containing heterocyclics that play a key role in binding at target sites for potential antidepressant action. The in silico studies were carried out to determine the binding interactions of the target ligands with the receptor site to determine the potential role of substitution patterns at core pharmacophoric features. This article will help medicinal chemists, biochemists, and other interested researchers in identifying the potential pharmacophores as lead compounds for further development of new potent antidepressants. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics (AP) have been used to augment antidepressant (AD) medication in treatment‐resistant depression. In this study we examined factors (including severity of depression and initial antidepressant) affecting AP augmentation, as well as which APs were initiated as augmentation in young adults. Methods: Data were extracted from Finnish nationwide registers. Of persons aged 18–29 years diagnosed with a depression during 2004–2017 we focused on incident AD users (who initiated AD 6 months before and after the diagnosis) whose severity level of depression was recorded (N = 21,966). AP augmentation was studied during 1 year after diagnosis of depression. Persons diagnosed with severe depression with psychotic features (n = 1486) were excluded from main analyses and analyzed separately. Results: Overall, 8.4% of new antidepressant users initiated AP augmentation. Risk of augmentation increased with severity of depression as 3.9%, 5.8%, and 14.0% of persons with mild, moderate, and severe depression, respectively, initiated augmentation. Male sex, comorbid anxiety and personality disorders, substance abuse and selfharm/suicide attempt were positively associated with augmentation. Compared to citalopram, use of tricyclic antidepressant, paroxetine and venlafaxine were associated with increased risk of augmentation, while use of bupropion was associated with a decreased risk. Quetiapine and risperidone were the most common APs used in augmentation. Among persons with severe depression with psychotic features, use of sertraline was associated with AP augmentation, whereas use of fluoxetine decreased risk of augmentation. Conclusions: Use of APs as augmentation of AD therapy was common in severe depression. Comorbidities had only a small effect to augmentation, but selection of initial AD was more closely associated to risk of augmentation. Interestingly, use of bupropion decreased risk of augmentation, which warrants further studies, as well as the decrease in risk of augmentation when fluoxetine in case of psychotic depression was used. [ABSTRACT FROM AUTHOR]

Introduction: Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and costs. Methods: A population-based registry study was conducted to assess nonadherence and to analyze the economic burden of treatment and from nonadherence to antidepressants in 2021. Non-adherence was measured by the Medication Possession Ratio and those below 80% were classified as nonadherent. Results: In 2021, 246,718 patients (10.60% [95% CI: 10.48-10.72]) received antidepressants at a cost of €29 million. The median antidepressant cost per patient/year was €70.08€, ranging from €7.58 for amitriptyline to €396.66 for agomelatine. Out-of-pocket costs represented 6.09% of total expenditures, with a median copayment of €2.78 per patient. The 19.87% [95% CI 19.52-20.22)] of patients were non-adherent to antidepressants, costing €3.9 million (13.30% of total antidepressant costs). Non-adherence rates exceeded 20% for the tricyclic antidepressants, fluoxetine (23.53%), fluvoxamine (22.42%), and vortioxetine (20.58%). Venlafaxine (14.64%) and citalopram (14.88%) had the lowest nonadherence rates, of less than 15%. The median cost of non-adherent medications per patient/year was €18.96 and ranged from €2.50 (amitriptyline) to €133.42 (agomelatine). Conclusion: Reducing non-adherence to antidepressants is critical to improving clinical and economic outcomes. The implementation of interventions and standardized measures, including early detection indicators, is urgently needed. Antidepressants differ with regard to non-adherence and their cost, and this should be considered when prescribing this medication. The Medication Possession Ratio could be used by the healthcare provider and clinician to identify non-adherent patients for monitoring, and to take necessary corrective actions. [ABSTRACT FROM AUTHOR]

Depression, as a common mental illness that is often accompanied by suicidal and homicidal behaviors, is one of the most important diseases in the medical field that requires urgent attention. The pathogenesis of depression is complex, and the current therapeutic drugs such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, and secondary serotonin reuptake inhibitors have certain shortcomings. The inflammatory factor hypothesis, one of the pathogenesis of depression, suggests that inflammatory response is a key factor leading to the occurrence and development of depression, and that overactivation of inflammatory factors such as NLRP3, Toll-like receptor 4, and IDO leads to immune-system dysfunction and depression. The other pathogenic hypothesis, the gut flora hypothesis, has also been the focus of recent research. The gut flora may work together with inflammatory factors to cause depression. The approach to treating depression has been by altering the gut flora through drugs or probiotics. However, effective and clear treatment methods are lacking. In this study, by exploring the involvement of intestinal flora and inflammatory factors in the pathogenesis of depression, we found that improving the intestinal flora can affect inflammatory factors and, therefore, provide research ideas for the development of novel drugs to treat depression. [ABSTRACT FROM AUTHOR]

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Background: Electroacupuncture (EA) is a promising therapy for depression. However, a comprehensive review of EA for depression is needed. Methods: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) guidelines to evaluate the efficacy and safety of EA for depression. Potentially relevant trials and reviews were searched in MEDLINE, EMBASE, PsycINFO, and CENTRAL from inception to March 2022. EA alone and combined with other therapy were eligible for inclusion. The severity of depression during and after treatment and the number of adverse events were assessed as outcomes. Risk of bias (ROB) evaluation, subgroup analysis, sensitivity analysis, reporting bias assessment, and GRADE system evaluation were also conducted. Results: Thirty-four trials were included. The overall ROB was medium. Low-quality evidence showed that the efficacy of EA was not less than that of antidepressants [EA + selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)] and manual acupuncture (MA). EA and EA + SSRIs had better efficacy than SSRIs alone in decreasing the severity of depression during the early treatment. Moderate-quality evidence also showed that EA and EA + SSRIs were safer than SSRIs alone. Sensitivity analysis was mostly not feasible. Major publication bias was unlikely. Conclusion: These results indicate that the efficacy of EA is not less than that of antidepressants and MA. Moreover, EA and EA + SSRI treatments show a more rapid onset and greater safety than SSRIs. More high-quality trials are needed for further confirmation. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort. Purpose: To determine (1) the effects of serotonin reuptake inhibitors in pseudarthrosis rates after anterior cervical decompression and fusion (ACDF) and (2) to identify patient-reported outcome measures in patients taking serotonin reuptake inhibitors. Overview of Literature: Recent literature suggests that selective serotonin reuptake inhibitors (SSRIs) may inhibit fracture healing via downregulation of osteoblast differentiation. Spinal fusion supplementation with osteoblast-rich substances enhances spinal fusion, thus SSRIs may be detrimental. Methods: Patients with 1-year postoperative dynamic cervical spine radiographs following ACDF were grouped into serotonin reuptake inhibitor prescriptions (SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) and no prescription (atypical antidepressant or no antidepressant). Pseudarthrosis was defined as =1 mm interspinous process motion on dynamic radiographs. Logistic regression models were controlled for confounding to analyze pseudarthrosis rates. Alpha was set at p - values of <0.05. Results: Of the 523 patients who meet the inclusion criteria, 137 (26.2%) were prescribed an SSRI, SNRI, or TCA. Patients with these prescriptions were more likely to have pseudarthrosis (p =0.008) but not a revision surgery due to pseudarthrosis (p =0.219). Additionally, these patients had worse 1-year postoperative mental component summary (MCS)-12 (p =0.015) and Neck Disability Index (NDI) (p =0.006). The multivariate logistic regression analysis identified SSRI/SNRI/TCA use (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.11-2.99; p =0.018) and construct length (OR, 1.91; 95% CI, 1.50-2.44; p <0.001) as pseudarthrosis predictors. A SSRI/SNRI/TCA prescription was a revision surgery predictor due to adjacent segment disease on univariate analysis (OR, 2.51; p =0.035) but not on multivariate logistic regression analysis (OR, 2.24; p =0.10). Conclusions: Patients taking serotonin reuptake-inhibiting antidepressants are at increased risk of worse postoperative outcome scores, including NDI and MCS-12, likely due to their underlying depression. This may contribute to their greater likelihood of having adjacent segment surgery. Additionally, preoperative use of serotonin reuptake inhibitors in patients undergoing an ACDF is a predictor of radiographic pseudarthrosis but not pseudarthrosis revision. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate and categorize the survival benefit of tricyclic antidepressants (TCAs) in lung cancer patients based on systematic computational drug repositioning data. METHODS: Data were retrospectively extracted from the medical records of non-small cell lung cancer (NSCLC) patients from the University of Cincinnati Cancer Medical Center database. Patients receiving antidepressants during their course of anti-cancer treatment were compared with those without antidepressants. Data were analyzed using Kaplan–Meier survival curves with the log-rank test, and overall survival (OS) was calculated from the date of diagnosis until last follow-up or death. RESULTS: The median OS at 2 and 5 years for patients on antidepressants was 20.3 months (54.7% and 42%) vs 44.3 months (47.6% and 43.2%), which was not significant. The median OS for patients receiving TCAs, selective serotonin reuptake inhibitors, and other antidepressants was 3.17 months, 31.33 months, and 18.50 months, respectively. CONCLUSION: We found no significant survival benefit for TCA use in combination with anti-cancer agents in NSCLC patients.

• Depression, usually treated with antidepressants, is common in older adults with dementia. • Previous evidence does not support antidepressant use for older adults with dementia. • An increase in depression research may provide updated evidence, motivating this review. • The updated evidence found in this review does not support using antidepressants. Depression and dementia represent significant health challenges in older adults. Despite guidelines recommending antidepressants, their efficacy in depressed patients with dementia remains undetermined. This review, in following a living systematic review approach , primarily aims to determine the effect of any-type antidepressant on the level of depressive symptoms in older adults with dementia and secondly if there is an effect of any-type antidepressants on cognitive state, quality of life, and functionality in the old-age population with dementia. Systematic review and meta-analysis of RCTs from Medline, Embase, and Cochrane Register. Participants were ≥65 years, with both depression and any type of dementia. Certainty-of-Evidence was assessed through the Cochrane Risk-of-Bias tool and GRADE. Analysis involved standardized mean difference, with 95 % confidence-intervals (CIs). Of the 27,771 screened articles, 8 studies (617 participants), treated with SSRI, SSNRI, atypical, and tricyclic antidepressants were retained for quantitative synthesis. No evidence for an effect was found (SMD −0.10 [−0.26, 0.07]), nor when subgrouped based on depression severity or dementia level, nor for secondary outcomes. This review did not find evidence of a clinical effect of antidepressants for treating depression in older adults with dementia. Methodological challenges might contribute to this finding. [ABSTRACT FROM AUTHOR]

Antidepressants are a commonly prescribed psychotropic medication, and their use has increased in recent years. Medication non-adherence in patients with mental disorders is associated with worse health outcomes. A population-based registry study to assess antidepressant non-adherence during 2021 has been carried out. An indirect method based on the medication possession ratio (MPR) has been utilized. Patients with a MPR under 80% were classified as non-adherent. A multivariate logistic regression to identify non-adherence predictors has been used, considering sociodemographic (age, sex, institutionalization and urbanicity) and health related variables (diagnostics, antidepressant class, multiple prescribers, and polypharmacy). In 2021, 10.6% of the Castile and Leon population used antidepressants. These patients were institutionalized (7.29%), living in urban areas (63.44%), polymedicated with multiple prescribers (57.07%), and using serotonin selective reuptake inhibitors (SSRIs) (54.77%), other antidepressants (46.82%) or tricyclic antidepressants (TCAs) (13.76%). Antidepressants were prescribed mainly for depression (36.73%) and anxiety (29.24%). Non-adherence to antidepressants was more frequent in men (20.56%) than in woman (19.59%) and decreased with increasing age (32% up to 17 years old vs. 13.76% over 80 years old). TCAs were associated with the highest prevalence of non-adherence (23.99%), followed by SSRIs (20.19%) and other antidepressants (18.5%). Predictors of non-adherence in patients on antidepressants were: living in urban areas, using TCAs, and pain occurrence. Non-adherence to antidepressants decreases with aging. Being female, institutionalization, being polymedicated and having depression/anxiety alongside another psychiatric diagnosis are protective factors against non-adherence. The MPR is a robust indicator for the clinician to identify non-adherent patients for monitoring, and adopt any necessary corrective actions. [ABSTRACT FROM AUTHOR]

Depression is a condition characterized by low mood and an aversion to activity, that causes behavioral problems, poor quality of life and limits daily life activities. It is considered as the fourth leading cause of disability worldwide. Selective Serotonin Reuptake Inhibitors (SSRIs) Monoamine Oxidase (MAO) inhibitors, Tricyclic Antidepressants (TCAs), and atypical antidepressants are some of the conventional medications used to treat depression. However, only about half of patients with major depressive disorder (MDD) respond effectively to first-line antidepressant therapy. Additionally, there are a number of drawbacks to standard antidepressants, such as anti-cholinergic side effects, drug-drug interactions, and food-drug interactions, which prompts researchers to look at alternative approaches to the treatment of depression. Medicinal plants and their metabolites are extensively tested for their efficacy against depression. Electronic databases such as Google scholar, Science Direct, SciFinder and PubMed were used to search relevant literature on the role of polyphenols in depression. Plants-derived Polyphenols represent a major class of compounds extensively distributed in plants. Number of polyphenols have demonstrated antidepressant activity, among which berberine, piperine, curcumin, naringenin, ascorbic acid and ginsenosides are extensively evaluated. The medicinal plants and their derived compounds mediated synthesized green nanoparticles have also exhibited considerable efficacy in the management of depression. The therapeutic effects of these phytochemicals is mediated via differentiation and inhibition of neuronal cell apoptosis, promotion of neuronal cell survival and modulation of key neurotransmitters. The aim of this study is to review compressively the chemical, pharmacological and neurological evidence showing the potential of polyphenols in depression. [ABSTRACT FROM AUTHOR]

Patients with rheumatoid arthritis (RA) experience pain from inflammation, joint destruction, and neuropathy. Antidepressants may play a role among patients with RA and depression, fibromyalgia, or neuropathy to achieve desired outcomes. This commentary evaluated evidence for medications individually and identified important variables for future research. While we await the results of well-designed studies, a trial of duloxetine or milnacipran may be considered for patients with remnant pain and RA remission. Research is needed to evaluate the efficacy and safety of serotonin–norepinephrine reuptake inhibitors and tricyclic antidepressants in patients with RA and associated comorbid conditions. [ABSTRACT FROM AUTHOR]

Rationale: Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression.In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine.Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity.RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females.Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.Objectives: Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression.In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine.Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity.RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females.Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.Methods: Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression.In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine.Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity.RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females.Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.Results: Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression.In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine.Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity.RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females.Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.Conclusion: Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression.In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine.Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity.RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females.Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation. [ABSTRACT FROM AUTHOR]

• Antidepressant use was associated with an overall decreased risk of ovarian cancer. • The risk reduction was larger among postmenopausal women and long-term users. • The effect was most prominent for serous ovarian cancers. • Selective serotonin reuptake inhibitors showed the strongest risk reduction. • Oral contraceptive use and hormone replacement therapy both modified the association. Given that the evidence regarding the link between antidepressant use and ovarian cancer risk is equivocal, we investigated this research question by conducting two nationwide nested case-control studies among the Danish and Swedish populations. Altogether, 14,121 women with epithelial ovarian cancer (30–84 years old) (Denmark: 8976 diagnosed 2000–2019, Sweden: 5145 diagnosed 2010–2018) were randomly age-matched with 564,840 female controls (359,040 from Denmark, and 205,800 from Sweden) using risk set sampling. We used conditional logistic regression to estimate odds ratios (OR) with 95 % confidence intervals (CI) and combined the estimates based on the fixed-effect assumption. We also investigated potential effect modification by well-established risk factors for ovarian cancer. Antidepressant use was associated with an overall reduced risk of ovarian cancer (OR = 0.92, 95%CI: 0.88–0.96), and that reduction was more pronounced in postmenopausal women and long-term users. The effect was most pronounced for serous ovarian tumors (OR = 0.90, 95%CI: 0.86–0.95) but was also observed in other subtypes, although not statistically significant. Among different types of antidepressants, selective serotonin reuptake inhibitors in general and citalopram in particular exhibited a noteworthy reduction in ovarian cancer risk (OR = 0.89, 95%CI: 0.82–0.96). Additionally, use of oral contraceptives and hormone replacement therapy individually modified the association between antidepressant use and ovarian cancer risk. Use of an antidepressant was associated with a slight, but statistically significant, decrease in ovarian cancer risk. Given the morbidity and mortality associated with ovarian cancer, and increasing use of antidepressants, these findings may be of significance to cancer prevention and should be studied in more detail mechanistically. [ABSTRACT FROM AUTHOR]

Summary: Background: Despite high rates of depression and anxiety, little is known about the use of antidepressants amongst individuals diagnosed with inflammatory bowel disease (IBD). Aims: To evaluate temporal trends in the use of antidepressants; rates of antidepressant initiation and adherence of antidepressant use to international guidelines amongst individuals with IBD. Methods: This is a study of 14,525 incident IBD cases from 2004 to 2016 compared with 58,027 controls matched 1:4 for age and sex from the Clinical Practice Research Datalink. After excluding tricyclic antidepressants, we performed a Cox regression analysis to determine the risk associated with antidepressant use and logistic regression analysis to determine risk associated with antidepressant undertreatment. Results: Antidepressant use amongst individuals with IBD increased by 51% during the 12‐year study period, who were 34% more likely to initiate antidepressants in the year after IBD diagnosis compared with controls (aHR:1.34, 95% CI 1.21‐1.49). In those with IBD starting antidepressants, 67% received treatment lasting less than the duration recommended in international guidelines, of which 34% were treated for 1 month or less. 18‐24 year olds were twice as likely to discontinue treatment within 1 month compared with those aged 40‐60 years (aHR:2.03, 95% CI 1.40‐2.95). Socioeconomic deprivation was also associated with early treatment discontinuation (aHR:1.40, 95% CI 1.07‐1.83). Conclusions: In the year following IBD diagnosis individuals are significantly more likely to start antidepressants compared with controls, but treatment duration fell short of recommendations in the majority. Better integration of services may benefit individuals with IBD and psychiatric comorbidity. [ABSTRACT FROM AUTHOR]

Mental health disorders are independent risk factors for adverse perinatal and neonatal outcomes. It is estimated that 20% of women may experience symptoms of mental health disorders during or following pregnancy. It is important that obstetricians recognize the presentation of these symptoms and follow pathways for managing these conditions. This article utilizes case vignettes to describe the epidemiology, role of the multi-disciplinary team, clinical presentation, and management of common perinatal mental health disorders both from the obstetric and psychiatric view point. Indications and duration of psychotropic medications including side effects are also discussed as well as safety in pregnancy and lactation. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that microglial activation plays a key role in the pathogenesis of depression. In fact, neuroinflammation is associated with a phenotypic change of microglia, consisting of morphological differences, increased release of cytokines and oxidative stress products, which may contribute to the development and maintenance of depression. Antidepressants, including selective serotonin re-uptake inhibitors and serotonin–norepinephrine reuptake inhibitors, have been shown to act on the immune and oxidative stress mechanisms commonly found to be disrupted in depression. Thus, the inhibition of microglial activation may be one of the mechanisms through which they exert an antidepressant action. Aim: This is the first review summarising in vitro and ex vivo studies investigating the effects of different classes of antidepressants on microglia activation, by examining cellular changes and/or via measuring the production of immune and/or oxidative stress signalling molecules, in microglia models of neuroinflammation with either lipopolysaccharide (LPS) or cytokines. A total of 23 studies were identified, 18 using LPS stimulation and 5 using cytokines stimulation. Results: Overall, the studies show that antidepressants, such as selective serotonin re-uptake inhibitors, serotonin–norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants prevented microglial activation, including reduced microglial reactivity and decreased immune and oxidative stress products, in both models. However, specific antidepressants, such as bupropion and agomelatine did not prevent interferon-gamma (IFN-γ)-induced microglial activation; and for other antidepressants, including phenelzine, venlafaxine and sertraline, the results of different studies were inconsistent. Conclusions: Overall, results summarised in this review support the hypothesis that the action of at least certain classes of antidepressants may involve regulation of microglial activation, especially when in presence of increased levels of inflammation. [ABSTRACT FROM AUTHOR]

Background: Central post-stroke pain (CPSP) is a type of neuropathic pain caused by dysfunction in the spinothalamocortical pathway. However, no animal studies have examined comorbid anxiety and depression symptoms. Whether the typical pharmacological treatments for CPSP, which include antidepressants, selective serotonin reuptake inhibitors (SSRIs), and anticonvulsants, can treat comorbid anxiety and depression symptoms in addition to pain remains unclear? The present study ablated the ventrobasal complex of the thalamus (VBC) to cause various CPSP symptoms. The effects of the tricyclic antidepressants amitriptyline and imipramine, the SSRI fluoxetine, and the anticonvulsant carbamazepine on pain, anxiety, and depression were examined. Results: The results showed that VBC lesions induced sensitivity to thermal pain, measured using a hot water bath; mechanical pain, assessed by von Frey test; anxiety behavior, determined by the open-field test, elevated plus-maze test, and zero-maze test; and depression behavior, assessed by the forced swim test. No effect on motor activity in the open-field test was observed. Amitriptyline reduced thermal and mechanical pain sensitivity and anxiety but not depression. Imipramine suppressed thermal and mechanical pain sensitivity, anxiety, and depression. Fluoxetine blocked mechanical but not thermal pain sensitivity, anxiety, and depression. However, carbamazepine did not affect pain, anxiety, or depression. Conclusion: In summary, antidepressants and SSRIs but not anticonvulsants can effectively ameliorate pain and comorbid anxiety and depression in CPSP. The present findings, including discrepancies in the effects observed following treatment with anticonvulsants, antidepressants, and SSRIs in this CPSP animal model, can be applied in the clinical setting to guide the pharmacological treatment of CPSP symptoms. [ABSTRACT FROM AUTHOR]

The antidepressant actions of deep brain stimulation (DBS) are associated with progressive neuroadaptations within the mood network, modulated in part, by neurotrophic mechanisms. We investigated the antidepressant-like effects of chronic nucleus accumbens (NAc) DBS and its association with change in glycogen synthase kinase 3 (GSK3) and mammalian target of rapamycin (mTOR) expression in the infralimbic cortex (IL), and the dorsal (dHIP) and ventral (vHIP) subregions of the hippocampus of antidepressant resistant rats. Antidepressant resistance was induced via daily injection of adrenocorticotropic hormone (ACTH; 100 μg/day; 15 days) and confirmed by non-response to tricyclic antidepressant treatment (imipramine, 10 mg/kg). Portable microdevices provided continuous bilateral NAc DBS (130 Hz, 200 μA, 90 μs) for 7 days. A control sham electrode group was included, together with ACTH- and saline-treated control groups. Home cage monitoring, open field, sucrose preference, and, forced swim behavioral tests were performed. Post-mortem levels of GSK3 and mTOR, total and phosphorylated, were determined with Western blot. As previously reported, ACTH treatment blocked the immobility-reducing effects of imipramine in the forced swim test. In contrast, treatment with either active DBS or sham electrode placement in the NAc significantly reduced forced swim immobility time in ACTH-treated animals. This was associated with increased homecage activity in the DBS and sham groups relative to ACTH and saline groups, however, no differences in locomotor activity were observed in the open field test, nor were any group differences seen for sucrose consumption across groups. The antidepressant-like actions of NAc DBS and sham electrode placements were associated with an increase in levels of IL and vHIP phospho-GSK3β and phospho-mTOR, however, no differences in these protein levels were observed in the dHIP region. These data suggest that early response to electrode placement in the NAc, irrespective of whether active DBS or sham, has antidepressant-like effects in the ACTH-model of antidepressant resistance associated with distal upregulation of phospho-GSK3β and phospho-mTOR in the IL and vHIP regions of the mood network. [ABSTRACT FROM AUTHOR]

Introduction: Depression often affects people suffering from serious illnesses, including oncological and palliative patients. It reduces their quality of life and worsens their prognosis. This is why it is so important to properly treat depression in palliative patients. Material and Methods: The information provided was collected as a result of analysis of various articles and textbooks on development, diagnosis and treatment, as well as prevention of depression in terminally ill patients using Google Scholar and PubMed databases. Results: The results show that the most common drug in therapy for palliative patients with depression are the sluggish serotonin reuptake inhibitors (SSRIs). SSRIs inhibit serotonin transporter reducing serotonin reuptake. This raises the level of neurotransmitter - serotonin - in the synaptic cleft. They are well tolerated and have fewer side effects than older antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors). Tricyclic antidepressants may relieve neuropathic pain and they are also beneficial for patients with insomnia. Mirtazapine in addition to antidepressant effects also causes increasing appetite, reducing nausea and sedative effect. In cancer-diagnosed patients particular attention should be paid to side effects such as nausea and vomiting that may occur in patients undergoing radiotherapy and chemotherapy using SSRIs or TCAs. SSRI therapy have a good safety profile and also interacts less frequently, while atypical antipsychotics may reduce the discomforts of taking chemotherapy. An alternative method of treating depression is the use of psychostimulants such as methylphenidate. Another way to treat depression is psychotherapy. Conclusions: There are several options for treating depression in palliative patients. It is important to pay attention to the side effects of prescribed medicines. Nevertheless, the best results are obtained by combining pharmacotherapy with psychotherapy.

Depression is an affective disease with a complex clinical picture that is characterized by mood and emotional disturbances. It is known that several factors contribute to the risk of developing depression. The concept that mitochondrial dysfunction is one of the causes of depression is supported by a wide range of studies on cell cultures, animal models, and clinical research. An understanding the relationship between mitochondrial processes and central nervous system abnormalities that occur in the course of depression can guide the development of novel mitochondrial targeted therapeutic strategies as well as the usage of currently available antidepressants in a new context. This brief review aims to summarize recent findings on mitochondria dysfunction in depression, provide insight into therapeutic strategies targeting mitochondrial pathways, allude to future promising therapies, and discuss factors that can be used to improve treatment outcomes. The main focus is on new aspects (the effects of nutraceuticals and physical activity on brain metabolism), which can be combined with the available treatment options [monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and atypical drugs] to enhance their therapeutic effects. [ABSTRACT FROM AUTHOR]

A biopsychosocial and lifestyle approach should be used when managing depression. Many patients seen in primary care do not require drug therapy. Evidence-based treatments such as psychological therapies and antidepressant drugs are effective for depression. All patients should receive education about depression. Shared decision making with the patient is critical if an antidepressant is prescribed. The choice of antidepressant depends on its efficacy and tolerability, the depressive presentation, patient preference and drug interactions. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to estimate the features of suicide rate and its association with antidepressant prescriptions during the past decade in China. Methods: Official data on suicides were obtained and stratified by four age groups, gender, urban/rural areas, and regions (East, Central, and West). The annual antidepressant prescriptions were expressed in pills per 100 persons calculated as the volume of prescriptions divided by the total population. Negative binomial regression was carried out to examine the association between suicide and other variables. Results: Suicide rates in each stratum typically decreased from 2008 to 2015, while annual antidepressant prescriptions were generally increased by the year. The suicide rate increased with age and was greater in adult males than in females; higher in the central area and greater in rural than in urban areas. Suicide rates are negatively associated with antidepressant prescriptions including selective serotonin reuptake inhibitors (Incidence rate ratio [IRR] 0.983, 95% confidence interval [CI] 0.983–0.983), serotonin–norepinephrine reuptake inhibitors (IRR 0.951, 95% CI 0.951–0.951), tricyclic antidepressant (IRR 0.925, 95% CI 0.925–0.925) and total antidepressants (IRR 0.990, 95% CI 0.990–0.990) during 2008–2012. Conclusion: Suicide varied among different studied stratum. Suicide rates are negatively associated with antidepressant prescriptions. [ABSTRACT FROM AUTHOR]

Objective: This study investigated which comorbidities or comedications increased the probability of receiving quetiapine extended-release formulation (quetiapine XR) as an add-on treatment.Methods: Danish administrative registers were used as data sources. The study period was from 01 January 2011 to 01 July 2017. New users of selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), atypical antidepressants (AAD), and tricyclic antidepressants (TCA) aged ≥65 years were included in the study population. A multivariable Cox regression model was used to find predictors for receiving quetiapine XR add-on within the first year of antidepressant therapy.Results: A total of 123 655 new users of SSRI, SNRI, TCA, and AAD were eligible. The study population was composed of 57.7% females and the mean age was 77.2 years (SD 7.9 years). SSRI users comprised 49.6% of the study population. Among users of antidepressants, 171 (0.14%) patients received quetiapine XR as add-on treatment. In the adjusted analyses, female patients (HR 0.70; 95%CI 0.52-0.95) and glucocorticoid users (HR 0.41; 95%CI 0.21-0.80) had a significantly lower hazard of receiving quetiapine XR. Patients with dementia (HR 2.43; 95%CI 1.52-3.87) had a significantly higher hazard of receiving quetiapine XR than patients without this condition. When compared with SSRI users, AAD (HR 1.80; 95%CI 1.31-2.46) and TCA users (HR 0.18; 95%CI 0.06-0.49) had an increased/reduced hazard of receiving quetiapine XR, respectively.Conclusions: This study suggests that the choice of prescribing quetiapine add-on is driven by patient's differences in comorbidities, comedications and the type of antidepressant drug. [ABSTRACT FROM AUTHOR]

Objective: Few studies have longitudinally followed trends in antidepressant prescribing for Canadian children following the Black Box warning issued in 2004. Using a national data source, we aim to describe trends in antidepressant recommendations for Canadian children ages 1-18 during 2012 to 2016. Methods: A database called the Canadian Disease and Therapeutic Index (CDTI), provided by IQVIA, was used to conduct analyses. The CDTI dataset collects a quarterly sample of pediatric antidepressant recommendations, projected using a weight procedure from a dynamic sample of 652 Canadian office-based physicians. The term "recommendations" is used because nonprescription drugs may be recommended and there is no confirmation in the database that the prescriptions were filled or medications taken. The data were collected from 2012 to 2016 and the sample population was projected by IQVIA to be representative of the entire Canadian pediatric population. Results: The total number of projected antidepressant recommendations for children increased from 2012 to 2016. Selective serotonin reuptake inhibitors were the most recommended class of antidepressants. Analysis indicated that fluoxetine was the most frequently recommended drug. Findings also suggest that recommendations for tricyclic antidepressants (TCAs) are increasing, but predominantly for reasons other than treatment of depression. Conclusions: Overall, antidepressant use in Canadian children increased over the study period. Unsurprisingly, fluoxetine was the most recommended antidepressant for Canadian children. However, the observed increase in TCA use for a pediatric population is unexpected. The data source is descriptive and lacks detailed measures supporting comprehensive explanation of the findings, therefore, further research is required. [ABSTRACT FROM AUTHOR]

Background: Antidepressants may be used to manage a number of conditions in children and young people including depression, anxiety, and obsessive-compulsive disorder. UK guidelines for the treatment of depression in children and young people recommend that antidepressants should only be initiated following assessment and diagnosis by a child and adolescent psychiatrist. The aim of this study was to summarise visits to mental health specialists and indications recorded around the time of antidepressant initiation in children and young people in UK primary care.Methods: The study used linked English primary care electronic health records and Hospital Episode Statistics secondary care data. The study included 5-17-year-olds first prescribed antidepressants between January 2006 and December 2017. Records of visits to paediatric or psychiatric specialists and potential indications (from a pre-specified list) were extracted. Events were counted if recorded less than 12 months before or 6 months after the first antidepressant prescription. Results were stratified by first antidepressant type (all, selective serotonin reuptake inhibitors (SSRIs), tricyclic and related antidepressants) and by age group (5-11 years, 12-17 years).Results: In total, 33,031 5-17-year-olds were included. Of these, 12,149 (37%) had a record of visiting a paediatrician or a psychiatric specialist in the specified time window. The majority of recorded visits (7154, 22%) were to paediatricians. Of those prescribed SSRIs, 5463/22,130 (25%) had a record of visiting a child and adolescent psychiatrist. Overall, 17,972 (54%) patients had a record of at least one of the pre-specified indications. Depression was the most frequently recorded indication (12,501, 38%), followed by anxiety (4155, 13%).Conclusions: The results suggest many children and young people are being prescribed antidepressants without the recommended involvement of a relevant specialist. These findings may justify both greater training for GPs in child and adolescent mental health and greater access to specialist care and non-pharmacological treatments. Further research is needed to explore factors that influence how and why GPs prescribe antidepressants to children and young people and the real-world practice barriers to adherence to clinical guidelines. [ABSTRACT FROM AUTHOR]

Background: Primary care physicians and child and adolescent psychiatrists often treat sleep disturbances in children and adolescents with mood disorders using medications off-label, in the absence of clear evidence for efficacy, tolerability and short or long-term safety. This study is the first to report Canadian data about prescribing preferences and perceived effectiveness reported by child and adolescent psychiatrists regarding medications used to manage sleep disturbances in children and adolescents with depression. Methods: Canadian child and adolescent psychiatrists were surveyed on their perception of effectiveness of a range of medications commonly prescribed for sleep disturbances, their ranked preferences for these medications, reasons for avoiding certain medications, and perceived side effects. Results: Sixty-seven active child and adolescent psychiatrists completed the survey. Respondents reported noting significant sleep issues in 40% of all their patients. Melatonin and trazodone were identified as the first treatment of choice by 83% and 10% of respondents respectively, and trazodone was identified as the second treatment of choice by 56% of respondents for treating sleep disturbances in children and adolescents with depression. Melatonin (97%), trazodone (81%), and quetiapine (73%) were rated by a majority of respondents as effective. Doxepin, zaleplon, tricyclic antidepressants, zolpidem, or lorazepam were rarely prescribed due to lack of evidence and/or concerns about adverse effects, long-term safety, suitability for youth, suicidality, and dependence/tolerance. Conclusions: Melatonin and certain off-label psychotropic drugs are perceived as being more effective and appropriate to address sleep disturbances in children and adolescents with depression. More empirical evidence on the efficacy, tolerability and indications for using these medications and newer group of sleep medications in this population is needed. [ABSTRACT FROM AUTHOR]

Background: Understanding how patients are treated in the real-world is vital to identifying potential gaps in care. We describe the current pharmacologic treatment patterns for the treatment of depression. Methods: Patients with depression were identified from four large national claims databases during 1/1/2014–1/31/2019. Patients had ≥2 diagnoses for depression or an inpatient hospitalization with a diagnosis of depression. Patients were required to have enrollment in the database ≥1 year prior to and 3 years following their first depression diagnosis. Treatment patterns were captured at the class level and included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, and antipsychotics. Treatment patterns were captured during all available follow-up. Results: We identified 269,668 patients diagnosed with depression. The proportion not receiving any pharmacological treatment during follow-up ranged from 29 to 52%. Of the treated, approximately half received ≥2 different classes of therapy, a quarter received ≥3 classes and more than 10% received 4 or more. SSRIs were the most common first-line treatment; however, many patients received an anxiolytic, hypnotic/sedative, or antipsychotic prior to any antidepressive treatment. Treatment with a combination of classes ranged from approximately 20% of first-line therapies to 40% of fourth-line. Conclusions: Many patients diagnosed with depression go untreated and many others receive a non-antidepressant medication class as their first treatment. More than half of patients received more than one type of treatment class during the study follow up, suggesting that the first treatment received may not be optimal for most patients. [ABSTRACT FROM AUTHOR]

Objective: To compare antidepressant utilization in individuals aged 5–19 years from the Scandinavian countries. Methods: A population‐based drug utilization study using publicly available data of antidepressant use from Denmark, Norway, and Sweden. Results: In the study period from 2007 to 2017, the proportion of antidepressant users increased markedly in Sweden (9.3–18.0/1000) compared to Norway (5.1–7.6/1000) and Denmark (9.3–7.5/1000). In 2017, the cumulated defined daily doses (DDD) of selective serotonin reuptake inhibitors were 5611/1000 inhabitants in Sweden, 2709/1000 in Denmark, and 1848/1000 in Norway. The use of 'other antidepressants' (ATC code N06AX) also increased in Sweden with a higher DDD in 2017 (497/1000) compared to Denmark (225/1000) and Norway (170/1000). The use of tricyclic antidepressants was generally low in 2017 with DDDs ranging between 30–42 per 1000. The proportion of antidepressant users was highest among 15‐ to 19‐year‐old individuals. Girls were more likely to receive treatment than boys, and the treated female/male ratios per 1000 were similar in Sweden (2.39), Denmark (2.44), and Norway (2.63). Conclusion: Even in highly comparable healthcare systems like the Scandinavian countries', variation in antidepressant use is considerable. Swedish children and adolescents have a markedly higher and still increasing use of antidepressants compared to Danish and Norwegian peers. [ABSTRACT FROM AUTHOR]

Besides the memory impairment, Alzheimer’s disease (AD) is often complicated by neuropsychiatric symptoms also known as behavioral and psychological symptoms of dementia, which occur in one-third of patients at an early stage of the disease. Although the relationship between depressive disorders and AD is debated, the question if depression is a prodromal symptom preceding cognitive deficits or an independent risk factor for AD is still unclear. Moreover, there is growing evidence reporting that conventional antidepressants are not effective in depression associated with AD and, therefore, there is an urgent need to understand the neurobiological mechanism underlying the resistance to the antidepressants. Another important question that remains to be addressed is whether the antidepressant treatment is able to modulate the levels of amyloid-β peptide (Aβ), which is a key pathological hallmark in AD. The present review summarizes the present knowledge on the link between depression and AD with a focus on the resistance of antidepressant therapies in AD patients. Finally, we have briefly outlined the preclinical and clinical evidences behind the possible mechanisms by which antidepressants modulate Aβ pathology. To our opinion, understanding the cellular processes that regulate Aβ levels may provide greater insight into the disease pathogenesis and might be helpful in designing novel selective and effective therapy against depression in AD.

Background: Depression and anxiety may unfavorably impact on cardiac autonomic dysregulation. However, it is unclear whether this relationship results from a causal effect or may be attributable to confounding factors. We tested the relationship between depression and anxiety with heart rate (HR) and heart rate variability (HRV) across a 9-year follow-up (FU) period and investigated possible confounding by antidepressant use and genetic pleiotropy.Methods: Data (no. of observations = 6,994, 65% female) were obtained from the longitudinal Netherlands Study of Depression and Anxiety, with repeated waves of data collection of HR, HRV, depression, anxiety, and antidepressant use. Summary statistics from meta-analyses of genome-wide association studies were used to derive polygenic risk scores of depression, HR, and HRV.Results: Across the 9-year FU, generalized estimating equations analyses showed that the relationship between cardiac autonomic dysregulation and depression/anxiety rendered nonsignificant after adjusting for antidepressant use. A robust association was found between antidepressant use (especially tricyclic antidepressants, selective serotonin, and noradrenalin reuptake inhibitors) and unfavorable cardiac autonomic activity across all waves. However, no evidence was found for a genetic correlation of depression with HR and HRV, indicating that confounding by genetic pleiotropy is minimal.Conclusions: Our results indicate that the association between depression/anxiety and cardiac autonomic dysregulation does not result from a causal pathway or genetic pleiotropy, and these traits might therefore not be inevitably linked. Previously reported associations were likely confounded by the use of certain classes of antidepressants. [ABSTRACT FROM AUTHOR]

Many patients are prescribed antidepressants. This article discusses depression, as well as the available first- and second-line prescription medications used to manage the disorder in adults. [ABSTRACT FROM AUTHOR]

Besides the memory impairment, Alzheimer's disease (AD) is often complicated by neuropsychiatric symptoms also known as behavioral and psychological symptoms of dementia, which occur in one-third of patients at an early stage of the disease. Although the relationship between depressive disorders and AD is debated, the question if depression is a prodromal symptom preceding cognitive deficits or an independent risk factor for AD is still unclear. Moreover, there is growing evidence reporting that conventional antidepressants are not effective in depression associated with AD and, therefore, there is an urgent need to understand the neurobiological mechanism underlying the resistance to the antidepressants. Another important question that remains to be addressed is whether the antidepressant treatment is able to modulate the levels of amyloid-β peptide (Aβ), which is a key pathological hallmark in AD. The present review summarizes the present knowledge on the link between depression and AD with a focus on the resistance of antidepressant therapies in AD patients. Finally, we have briefly outlined the preclinical and clinical evidences behind the possible mechanisms by which antidepressants modulate Aβ pathology. To our opinion, understanding the cellular processes that regulate Aβ levels may provide greater insight into the disease pathogenesis and might be helpful in designing novel selective and effective therapy against depression in AD. [ABSTRACT FROM AUTHOR]

Background: The duration of antidepressant use affects the treatment of depression. Using the National Health Insurance database, which covers almost the entire national population, we verified the factors associated with the inadequate short-term use of initially prescribed antidepressants and their effects on the relapse and recurrence of depressive episodes. Methods: There were 752,190 patients included who had been newly prescribed antidepressants in 2012 with the diagnosis of depressive disorder. They were followed-up until December 31, 2015. They were classified as short-term and long-term antidepressant users depending on whether they used a specific initial antidepressant for at least four weeks. Sociodemographic, clinical, and medical utilization factors affecting the duration of antidepressant use were investigated. We also identified whether the duration of antidepressant use affected the risk of relapse and recurrence, which was defined by the restarting of antidepressants. Results: Initial antidepressants were taken for less than 28 days by 458,057 (60.84%) patients. Tricyclic antidepressants were used as the initial antidepressant more frequently than selective serotonin reuptake inhibitors (64.5% versus 19.3%). The type of initial antidepressant, polypharmacy, psychiatric and medical comorbidities, type of insurance coverage, and type of medical institution visited were associated with short-term use. Short-term use marginally increased the risk of relapse and recurrence of depressive episodes (Hazard ratio: 1.06, 95% confidence intervals 1.048–1.075). Conclusions: Short-term antidepressant use is widespread in Korea, and assessment in various aspects are necessary to set proper treatment plans. [ABSTRACT FROM AUTHOR]

Introduction: Minocycline is a tetracycline antibiotic drug that is receiving attention as an alternative for the treatment of depression. Several mechanisms have been proposed for this effect. The current study evaluated the involvement of the noradrenergic system in the antidepressant-like effect of minocycline. Materials and Methods: The total immobility time was evaluated as an index of depression in mice forced swimming test (FST). Minocycline (40 mg/kg) was injected for 3 days. Imipramine (5 mg/kg, a tricyclic antidepressant), prazosin (1 mg/kg, an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, an α2-adrenoceptor antagonist), and propranolol (2 mg/kg, a β-adrenoceptor antagonist) were injected 30 min before the last dose of minocycline, α-methyl-p-tyrosine (100 mg/kg, an inhibitor of tyrosine hydroxylase) was administered 4 h before minocycline final dose. Results: Minocycline decreased the immobility time during FST. The injection of prazosin prevented the antidepressant like effect of minocycline, while imipramine, yohimbine or propranolol potentiates the anti-depressant like effect of minocycline during the FST. Besides that, the pretreatment of mice with α-methyl-p-tyrosine did not change the minocycline antidepressant-like effect in the FST. Conclusion: The present study suggests that the noradrenergic system has a trivial role in the antidepressant-like effect of minocycline; the impact on neuroinflammation and cytokines might be more important. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of pharmaceutically treated depression (PTD) and treatment resistant depression (TRD) is largely unknown in South Korea. The aim of this study was to develop a greater understanding of the characteristics of PTD and TRD in nearly the entire adult population in South Korea using the Health Insurance Review and Assessment Service (HIRA). Method: Diagnostic codes and prescription data for South Korean adults were extracted from the HIRA. Subjects were included in the PTD cohort if they received at least one prescription for antidepressants and were diagnosed with depression. TRD was defined as PTD having two or more regimen failures of antidepressants or antipsychotics. Results: In 2012, there were 41,256,396 adults in South Korea with 834,694 meeting the criteria for PTD (2.0%). Among subjects with PTD, 57% stopped treatment in less than 28 days of antidepressant supply. Tricyclic and tetracyclic antidepressants were the most frequently used antidepressants as a first-line regimen for PTD (44.3% of PTD) followed by selective serotonin reuptake inhibitors (32.1% of PTD). Results also indicated that 34,812 subjects developed TRD (4.2% of PTD). Median PTD and TRD durations were 28 and 623 days respectively. Proportions of psychiatric and non-psychiatric comorbidities were higher in TRD cases than in PTD cases that were not treatment resistant. Conclusions: Despite a small proportion of patients with TRD, the prolonged duration of illness and higher comorbidity implies the need for better treatment. [ABSTRACT FROM AUTHOR]