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Purpose: To analyze the risk of dental implant failure for patients with a history of antidepressant use through a systematic review and meta-analysis. Materials and Methods: An electronic search was performed up to June 2023 in three databases including PubMed/MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials; data on the comparison of implant failure rate for patients with and without the use of antidepressants were included. Meta-analyses for the risk ratio of implant failure rate at patient level and implant level were performed. Results: Overall, 11 clinical studies were selected for inclusion in this review. The meta-analyses showed a risk ratio of 2.44 (95% CI = 1.75 to 3.39; P < .0001) and 2.44 (95% CI = 1.73 to 3.46; P < .0001) for the implant failure at patient level and implant level, respectively. The comparisons presented a low heterogeneity for the patient-level analysis and a moderate heterogeneity for the implant-level analysis among the pooled studies. Subgroup analyses also revealed that patients who received only selective serotonin reuptake inhibitors (SSRIs) or SSRIs with other types of antidepressants had a higher risk of implant failure than those who were not on any antidepressants. Conclusions: The current review demonstrates that the use of antidepressants such as SSRIs may increase the risk of dental implant failure at both patient level and implant level. Although limited evidence suggests that a certain type of SSRI (sertraline) may have more influence on implant failure than other SSRIs, future studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Narcolepsy is mainly associated with excessive daytime sleepiness, but the characteristic feature is abnormal rapid eye movement (REM) sleep phenomena. REM sleep disturbances can manifest as cataplexy (in narcolepsy type 1), sleep paralysis, sleep-related hallucinations, REM sleep behavior disorder, abnormal dreams, polysomnographic evidence of REM sleep disruption with sleep-onset REM periods, and fragmented REM sleep. Characterization of REM sleep and related symptoms facilitates the differentiation of narcolepsy from other central hypersomnolence disorders and aids in distinguishing between narcolepsy types 1 and 2. A circuit comprising regions within the brainstem, forebrain, and hypothalamus is involved in generating and regulating REM sleep, which is influenced by changes in monoamines, acetylcholine, and neuropeptides. REM sleep is associated with brainstem functions, including autonomic control, and REM sleep disturbances may be associated with increased cardiovascular risk. Medications used to treat narcolepsy (and REM-related symptoms of narcolepsy) include stimulants/wake-promoting agents, pitolisant, oxybates, and antidepressants; hypocretin agonists are a potential new class of therapeutics. The role of REM sleep disturbances in narcolepsy remains an area of active research in pathophysiology, symptom management, and treatment. This review summarizes the current understanding of the role of REM sleep and its dysfunction in narcolepsy.

Researchers have developed multiple approaches to treat major depressive disorder (MDD). Clinicians commonly employ antidepressant medication (ADM) and psychotherapy as treatment protocols. This review surveys the knowledge and identifies problems with the effects of personality and temperament for MDD treatment in 14 quantitative studies. High extraversion and conscientiousness have a positive effect on psychotherapy treatment while high neuroticism has a negative effect. Agreeableness and openness to experience appear to have conflicting results. All individual traits do not influence ADM treatment except for high and low reward dependence, which may be better for psychotherapy and ADM respectively. Low persistence and high harm avoidance adversely affect psychotherapy, but novelty seeking has an insignificant effect. Some problems in the literature include the self-report measures for individual traits, heterogeneity of study designs, and the complexity of defining personality and temperament. This paper is limited to ADM by SSRIs, SNRIs, and tricyclic antidepressants. These findings may assist patients in choosing treatment types and clinicians in creating better treatment plans for patients, especially psychotherapy. This article may also contribute to the reconceptualization of mental disorders as a dimension instead of a type.

Background: Depression affects approximately 280 million individuals globally and it is a leading cause of disability. Despite effective medication options, 50% of patients prematurely discontinue antidepressants within 6 months. We sought to understand patients' perspectives regarding their needs and expectations related to antidepressants. Objectives: To identify and describe enablers and barriers that influence adult patients' medication adherence in depression treatment and to explore patients' educational needs on initiating or continuing antidepressant therapy. Methods: Qualitative descriptive study was conducted using individual, semi-structured interviews of adult patients with depression who were prescribed an antidepressant within 3 months of study recruitment at an urban primary care clinic in Toronto, Canada. Thirteen participants were interviewed. Interviews were recorded and transcribed verbatim for inductive thematic analysis. Results: Six themes emerged: safety and effectiveness of antidepressant, understanding of depression and its management, medication administration, healthcare experiences in the treatment of depression, and social influences and relationships. Barriers to adherence included adverse effects of antidepressants, preference for non-pharmacological therapies, uncertainty about therapeutic effects, and social stigma. In contrast, enablers were positive responses from antidepressants, fear of relapse, reminder aids, established routine, and a trusting patient-provider relationship. Participants desired access to reliable, evidence-based, and personalized educational information delivered through verbal, written, and digital formats to support antidepressant adherence. Conclusion: To overcome the identified barriers, educational strategies should involve both patients and their prescribers to identify patient-specific needs and treatment goals, engage in shared decision-making, and maintain consistent follow-up to support antidepressant adherence. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) is a global health issue, and a significant portion of individuals with MDD experience Treatment-Resistant Depression (TRD), characterized by the lack of response to adequately trialed antidepressant medication and therapy. This systematic review aims to investigate the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) as an intervention for individuals with TRD. Materials and methods: We will conduct a thorough search for publications of randomized clinical trials and quasi-experimental studies in MEDLINE, Embase, PsycINFO, Web of Science databases, and ClinicalTrials.gov. Furthermore, reference lists of included studies will be manually screened for additional relevant articles, with no restrictions on language or publication date. The search will be conducted from the inception of the databases until June 2024. Our PICO-guided research questions are: (1) In adults with Treatment-Resistant Depression, is MBCT more effective than standard care or other active treatments in reducing depressive symptoms? (2) In adults with Treatment-Resistant Depression, does MBCT demonstrate a comparable safety profile to standard care or other active treatments? The quality of the included studies will be assessed independently using the Cochrane Risk of Bias Tool (RoB 2). This study seeks to evaluate the effectiveness and tolerability of Mindfulness-Based Cognitive Therapy as an intervention for Treatment-Resistant Depression, and will employ the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to appraise the confidence in the evidence. Prospero registration: Prospero registration ID:CRD42023411978. Registered on April 07, 2023. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population. A total of 2742 patients with MDD (males/females = 816/1926, aged 14–60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use. The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001). The cross-sectional design of this study precludes establishing causal relationships. Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD. • Prevalence of benzodiazepine use in patients with MDD in China is notably high. • Age is significantly associated with increased risks of benzodiazepine use. • Anxiety, depressive symptoms or sleep problem contribute to the use of benzodiazepine. [ABSTRACT FROM AUTHOR]

Functional impairment is common in patients with major depressive disorder (MDD). The Functioning Assessment Short Test (FAST) provides a detailed clinician-rated assessment of functioning across multiple aspects of daily life. This study aimed to establish clinically relevant response thresholds for the FAST in patients with MDD receiving antidepressant treatment. Data were derived from three 8-week clinical trials of antidepressant therapy in patients with MDD that included assessment of functioning using the FAST as a pre-specified endpoint. The minimal clinically important difference (MCID) and threshold for response in terms of change in FAST total score were determined using anchor-based methods. After 8 weeks of antidepressant treatment, the mean reduction in FAST total score in patients considered clinically minimally improved (Clinical Global Impression–Improvement [CGI-I] score of 3) was 7–9 points (~20 % reduction). The threshold for functional response (reduction in FAST total score from baseline in patients with a CGI-I score of ≤2 at week 8) was 16–19 points (~50 % reduction). The threshold for functional response was higher in patients with MDD and comorbid generalized anxiety disorder than in those with MDD alone (mean reduction in FAST total score at 8 weeks: 26 points [63 %]). Short-term studies. These results provide further validation of the FAST for assessing functioning in patients with MDD. In patients with MDD, the suggested MCID for FAST total score is 7–9 points and the proposed threshold for response is a reduction from baseline of approximately 50 %. • Patients with major depressive disorder (MDD) experience functional impairments that impact all aspects of their daily life • The Functioning Assessment Short Test (FAST) provides a detailed assessment of functional impairments in patients with MDD • In patients with MDD, the minimal clinically important difference in FAST total score after 8 weeks therapy was 7–9 points • A reduction in FAST total score of approximately 50 % after 8 weeks of antidepressant treatment was indicative of response • The threshold for functional response was higher in patients with comorbid anxiety than in those with MDD alone [ABSTRACT FROM AUTHOR]

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of >400 natural products with a broad spectrum of bioactivity, ranging from antidepressant and antimicrobial to anti-obesity and anticancer activity. Here, we present a scalable, regio-, site-, and enantioselective catalytic method for synthesis of cyclic b-prenyl ketones, compounds that can be used for efficient syntheses of many PPAPs in high enantiomeric purity. The transformation is prenyl conjugate addition to cyclic b-ketoesters promoted by a readily accessible chiral copper catalyst and involving an easy-to-prepare and isolable organoborate reagent. Reactions reach completion in just a few minutes at room temperature. The importance of this advance is highlighted by the enantioselective preparation of intermediates previously used to generate racemic PPAPs. We also present the enantioselective synthesis of nemorosonol (14 steps, 20% yield) and its one-step conversion to another PPAP, garcibracteatone (52% yield). [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Hypericumperforatum (HP) is a traditional herb that has been shown to have antidepressant effects, but its mechanism is unclear. This study aims to identify the molecular targets of HP for the treatment of MDD. Methods: We performed differential analysis and weighted gene co-expression network analysis (WGCNA) with blood mRNA expression cohort of MDD and healthy control to identify DEGs and significant module genes (gene list 1). Three databases, CTD, DisGeNET, and GeneCards, were used to retrieve MDD-related gene intersections to obtain MDD-predicted targets (gene list 2). The validated targets were retrieved from the TCMSP database (gene list 3). Based on these three gene lists, 13 key pathways were identified. The PPI network was constructed by extracting the intersection of genes and HP-validated targets on all key pathways. Key therapeutic targets were obtained using MCODE and machine learning (LASSO, SVM-RFE). Clinical diagnostic assessments (Nomogram, Correlation, Intergroup expression), and gene set enrichment analysis (GSEA) were performed for the key targets. In addition, immune cell analysis was performed on the blood mRNA expression cohort of MDD to explore the association between the key targets and immune cells. Finally, molecular docking prediction was performed for the targets of HP active ingredients on MDD. Results: Differential expression analysis and WGCNA module analysis yielded 933 potential targets for MDD. Three disease databases were intersected with 982 MDD-predicted targets. The TCMSP retrieved 275 valid targets for HP. Separate enrichment analysis intersected 13 key pathways. Five key targets (AKT1, MAPK1, MYC, EGF, HSP90AA1) were finally screened based on all enriched genes and HP valid targets. Combined with the signaling pathway and immune cell analysis suggested the effect of peripheral immunity on MDD and the important role of neutrophils in immune inflammation. Finally, the binding of HP active ingredients (quercetin, kaempferol, and luteolin) and all 5 key targets were predicted based on molecular docking. Conclusions: The active constituents of Hypericumperforatum can act on MDD and key targets and pathways of this action were identified. [ABSTRACT FROM AUTHOR]

AbstractPurpose/Aim of the studyMaterials and methodsResultsConclusionsThe pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment.MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks.Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks.These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment. [ABSTRACT FROM AUTHOR]

In the present work, we performed a computational study on hydroxamic acid containing compounds as acid sphingomyelinase (ASM) inhibitors. The study starts from the development of 3D‐QSAR and pharmacophore models, which were further taken as a source for the enumeration and virtual screening study. The 3D‐QSAR results showed the best statistical model with Q2, R2, and R2 scrambling values of 0.7175, 0.9019, and 0.7128, respectively. The pharmacophore hypothesis generated one of the best hypotheses including five features such as 2 aromatic rings, 2 hydrogen bond donors, and 1 hydrogen bond acceptor. The enumeration study paved the path in the discovery of novel compounds where pharmacophore hypothesis and 3D QSAR study data was used for the identification of novel compounds. Compound 9f_20 showed good docking score −11.399 and binding interactions with amino acids HIP317, ASN316, GLH386, Zn701, Zn702, HIP317, and HIP280 required for ASM inhibitory activity. The virtual screening study was performed on the basis of developed pharmacophore ADDRR_1 where ZINC000013941849 showed good binding interactions with receptor including amino acids Zn701, Zn702, HIP280, LYS103, HIP317, ASN316, and ILE487. ZINC000013941849 with docking score −13.101. The screened compounds may be taken for the further development of novel antidepressant agents. [ABSTRACT FROM AUTHOR]

Depression has emerged as a significant global health concern, exerting a profound impact on individuals, as evidenced by its high prevalence and associated suicide rates. Considering its pervasive nature, the absence of optimal treatment modalities remains a challenge. Acupuncture has garnered substantial clinical and experimental validation for its efficacy in addressing diverse forms of depression, including postpartum, post-stroke, and adolescent depression. This article endeavors to elucidate the distinctive attributes and underlying mechanisms of acupuncture in the contemporary treatment of depression. Research has demonstrated that acupuncture exerts diverse physiological effects in animal models of depression, encompassing modulation of the brain, serum, and brain-gut axis. These effects are attributed to various mechanisms, including anti-inflammatory and anti-oxidative actions, promotion of neuronal plasticity, neuroprotection, neurotrophic effects, modulation of neurotransmitters, regulation of endocrine and immune functions, and modulation of cell signal pathways. Currently, the therapeutic mechanism of acupuncture involves the engagement of multiple targets, pathways, and bidirectional regulation. Hence, acupuncture emerges as a promising alternative medical modality, exhibiting substantial research prospects and meriting comprehensive worth further study and dissemination. [ABSTRACT FROM AUTHOR]

Mood disorders, including depression, remain a significant global health concern, necessitating continuous efforts to develop novel and more effective antidepressant therapies. Although there have been significant advancements in comprehending the biology of Major Depressive Disorder (MDD), a considerable number of people suffering from depression do not exhibit positive responses to the pharmacologic treatments now available. This study specifically examines emerging targets and potential future approaches for pharmaceutical interventions in the treatment of MDD. The discussion revolves around novel therapeutic agents and their effectiveness in treating depression. The focus is on the specific pathophysiological pathways targeted by these agents and the amount of evidence supporting their use. While conventional antidepressants are anticipated to continue being the primary treatment for MDD in the foreseeable future, there is currently extensive research being conducted on numerous new compounds to determine their effectiveness in treating MDD. Many of these compounds have shown encouraging results. This review highlighted the recent advances in the synthesis of antidepressant derivatives and explores their pharmacologic insights for the treatment of mood disorders. [ABSTRACT FROM AUTHOR]

Background: The assessment of antidepressant and anxiolytic consumption and expenditures represents a reliable barometer of the burden of such mental health disorders and the effectiveness of relative healthcare services. Objectives: The current analysis aims to evaluate trajectories of consumption and expenditures of antidepressant and anxiolytic drugs to define patterns of usage and spending across 14 European countries between 2012 and 2021. Methods: A retrospective longitudinal study was performed based on pooled time series secondary data analysis over 2012/2021. Defined Daily Doses (DDD) per 1000 inhabitants and health expenditure per capita were analysed. Linear and quadratic trends were computed to determine relationships between the variables of interest. Results: Only 2 patterns of consumption/expenditure of antidepressants can be identified: consumption and expenditure both grow; consumption grows, and spending decreases. Consumption and expenditures registered 2 main patterns, decreasing in most European countries and increasing only in 2 cases. Conclusion: Prevailing patterns of consumption and spending show an increase in antidepressants and a decrease in anxiolytics. The variation in consumption of such drugs during this timeframe is attributable to several reasons, such as the epidemiological characteristics of mental disease, for instance, the prevalence and incidence of disorders, the accessibility of drugs and alternative treatments, like psychotherapy, different clinical practices and national guidelines. However, such analyses deserve attention for targeted policies and strategies for promoting mental health. [ABSTRACT FROM AUTHOR]

Natural products derived from various sources, including plants, have garnered significant interest as alternative therapeutic options. Among these, Tualang honey, extracted from the nectar of Tualang trees (Koompassia excelsa (Becc.) Taub.), has a long history of traditional use due to its therapeutic properties. This review aims to examine the pharmacological activities of Tualang honey, encompassing both in vitro and in vivo studies. A systematic search was conducted in multiple databases, including PubMed, Springer, Scopus, Wiley, and Science Direct, up until December 2022 to identify relevant studies on the pharmacological activities of Tualang honey. Two independent reviewers were involved in article selection, followed by data extraction and assessment of methodological quality using Syrcle's risk of bias tool. 123 articles were included, collectively describing the pharmacological activities of Tualang honey, including antimicrobial, anticancer, anti-inflammatory, antioxidant, antinociceptive, neuroprotective effects, and others. Tualang honey has significant promise as an alternative treatment option for treating a wide range of pathological diseases due to its wide range of pharmacological properties. Tualang honey's diverse array of pharmacological actions indicates its potential for multiple medicinal uses. [ABSTRACT FROM AUTHOR]

The association between depression and ambulatory care utilization is unclear. The authors sought to determine the association between untreated depression and ambulatory care utilization, including the extent to which care is fragmented, or spread across providers. The authors conducted a longitudinal study using data from the nationwide REasons for Geographic and Racial Differences in Stroke study linked to Medicare fee-for-service claims (N = 1412). They categorized participants into three study groups, based on self-reported depressive symptoms (Center for Epidemiological Studies Depression Scale score ≥ 4) and a medication inventory for antidepressants: Symptomatic Untreated (SU), Symptomatic Treated (ST), and Asymptomatic Treated (AT). The authors used descriptive statistics to characterize ambulatory care patterns by study group. They determined the association between the study group and fragmentation score (with high fragmentation defined as a reversed Bice–Boxerman Index ≥ 0.85) using multivariable logistic regression. All groups had similar numbers of primary care visits, but the SU group had the fewest specialist visits. The SU group had the lowest proportion of participants who received care from a psychiatrist (3.4% vs. 10.7% for ST and 11.9% for AT, pairwise P-values < 0.001). The SU group was the least likely to have highly fragmented care (adjusted odds ratio 0.68; 95% confidence interval 0.48, 0.95, compared with the ST group). These results suggest that older adults with untreated depression are not engaged in excess care-seeking behaviors. Rather, the results suggest undertreatment of depression in primary care and underutilization of psychiatric care. [ABSTRACT FROM AUTHOR]

Background: Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT. Aims: This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers. For the patients, it also investigated the relationship between antidepressant effects and six measures of acute drug effects. Methods: We compared data on acute psychedelic drug effects between 28 PAT patients with data from 28 healthy participants who participated in a randomized, double-blind crossover trial. All participants received varying doses of psilocybin and LSD. Subjective effects were assessed on an hourly basis during the acute drug effects, and the Mystical Experience Questionnaire (MEQ) was completed retrospectively. For patients, depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Results: Ratings of overall drug effect and mystical experience were similar across groups. Compared with healthy controls, patients reported lower ratings of ego dissolution. Patients showed a significant decrease in MADRS scores, and the greatest predictor of antidepressant outcome was relaxation during the PAT session. We did not observe a relationship between mystical-type experiences and antidepressant effects. Most patients experienced mild adverse effects which resolved within 48 h. Conclusion: PAT reduced depressive symptoms in this heterogeneous patient group. Patients may experience more challenging psychedelic effects and reduced ego dissolution. Hourly assessment of drug effects may predict clinical outcomes better than retrospectively assessed mystical experiences, and the impact of relaxation during PAT should be investigated further. [ABSTRACT FROM AUTHOR]

Depression is a mental illness that affects patients' behavior, and it impacts approximately 264 million people globally. Tetracyclic antidepressants (TeCAs) are one class of medication that is available for the treatment of depression. These medications work by modifying hormones such as serotonin, norepinephrine, and dopamine. TeCAs, such as setiptiline, amoxapine, mianserin, maprotiline, and mirtazapine, are four ring‐based compounds that assist in preventing the brain from reabsorbing the neurotransmitters norepinephrine and serotonin. Each of these medications interacts with adrenergic (α1 and α2) and serotonin (5HT1 and 5HT2) receptors independently. Using biological samples (plasma, blood, and urine) and pharmaceutical formulations, this review focuses on providing a complete overview of the various analytical conditions maintained for the medications in the above class and their metabolites. Major analytical methods such as mass spectrometry, gas chromatography, and high‐performance liquid chromatography are used to quantify and determine the drugs. This review provides a thorough understanding of impurity identification, pharmacokinetic and stability evaluations, and structural degradation quantification. It provides valuable and reliable information for research, enhancing their understanding of the subject matter. [ABSTRACT FROM AUTHOR]

The article discusses three randomized controlled trials (RCT) which focused on the use of brexpiprazole to treat the behavioral and psychological symptoms of dementia (BPSD). Topics explored include the brexpiprazole dosage administered which demonstrated improvement in symptoms, the treatment-emergent adverse events recorded following treatment, and a comparison between brexpiprazole and other antipsychotic medications in terms of effectiveness in managing BPSD.

Introduction: Seasonality in depressive and bipolar disorders, are recognized in the ICD-10/11 and DSM-5 diagnostic systems. The existence of a seasonal pattern of hospital diagnosis of major depression, bipolar disorder and prescription of antidepressant medications has not been evaluated in the Danish population. Methods: We retrieved date and year for all first-time hospital contacts with depression or bipolar disorder between 1999 and 2019, registered in the Danish National Patient Registry. Depression was defined using the ICD-10 F32-F33 codes, and for bipolar disorder the F30 or F31 codes. Date and year of all first-time purchases of antidepressant medications with ATC codes (N06A) between 1999 and 2021 were retrieved from the Danish National Prescription Registry, containing information on all prescribed drugs dispensed at pharmacies since 1995. Data on sunlight hours from 2012 to 2021 were retrieved from the Danish Metrological Institute. Results: Incidences of hospital diagnoses as well as purchases of medication varied with month and season. The monthly variations were larger for antidepressant medication and smallest for bipolar disorder. The multiple linear regression analysis showed that number of first-time diagnoses of depression or bipolar disorder did not correlate with season. For antidepressant medication the number of first-time prescriptions was significantly lower in summer compared to the winter season. Conclusion: This study found a seasonal variation of first-time prescriptions of antidepressant medication. We did not find a seasonal variation in first-time hospital diagnoses. Further research looking into depression severity, polarity of bipolar illness episodes, lag-time for sunlight exposure, and specific parts of the yearly photoperiods should be conducted. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness, tolerability, and safety of topical amitriptyline as a potential route of administration for the management of burning mouth syndrome. Background: Burning mouth syndrome is a complex, idiopathic, and debilitating orofacial pain disorder that impairs quality of life, with a prevalence of up to 18% in menopausal women. Available drugs to alleviate its burning sensation have inconsistent and limited efficacy. Given its physicochemical properties, excellent tolerability, and ability to target peripheral pathways, topical amitriptyline seems a promising mechanistically specific analgesic drug for burning mouth syndrome. Methods: In this retrospective cross‐sectional real‐world evidence study, patients with burning mouth syndrome who were prescribed topical amitriptyline for 8 weeks were identified. Eligibility criteria stemmed from ICHD‐3, ICOP, and consensus definitions. The primary outcome measure was mean daily pain intensity (on a 0–10 scale); secondary outcomes included adverse events and patient global impression of improvement. Data are given as the mean ± SD. Results: A total of 15 patients fulfilling the eligibility criteria were included and analyzed. Mean daily pain was 6.7 ± 2.1 at baseline and 3.7 ± 2.3 after treatment, with a mean reduction of 3.1 ± 2.8 (p = 0.002). Half of the patients experienced a decrease in pain by at least 50% (p = 0.008). Several mild adverse events were reported, such as somnolence or dry mouth. Conclusions: Topical amitriptyline may be a safe and potent route of administration in the treatment of burning mouth syndrome, a hypothesis to be tested in further controlled trials. [ABSTRACT FROM AUTHOR]

Objective: To develop machine learning models using patient and migraine features that can predict treatment responses to commonly used migraine preventive medications. Background: Currently, there is no accurate way to predict response to migraine preventive medications, and the standard trial‐and‐error approach is inefficient. Methods: In this cohort study, we analyzed data from the Mayo Clinic Headache database prospectively collected from 2001 to December 2023. Adult patients with migraine completed questionnaires during their initial headache consultation to record detailed clinical features and then at each follow‐up to track preventive medication changes and monthly headache days. We included patients treated with at least one of the following migraine preventive medications: topiramate, beta‐blockers (propranolol, metoprolol, atenolol, nadolol, timolol), tricyclic antidepressants (amitriptyline, nortriptyline), verapamil, gabapentin, onabotulinumtoxinA, and calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) (erenumab, fremanezumab, galcanezumab, eptinezumab). We pre‐trained a deep neural network, "TabNet," using 145 variables, then employed TabNet‐embedded data to construct prediction models for each medication to predict binary outcomes (responder vs. non‐responder). A treatment responder was defined as having at least a 30% reduction in monthly headache days from baseline. All model performances were evaluated, and metrics were reported in the held‐out test set (train 85%, test 15%). SHapley Additive exPlanations (SHAP) were conducted to determine variable importance. Results: Our final analysis included 4260 patients. The responder rate for each medication ranged from 28.7% to 34.9%, and the mean time to treatment outcome for each medication ranged from 151.3 to 209.5 days. The CGRP mAb prediction model achieved a high area under the receiver operating characteristics curve (AUC) of 0.825 (95% confidence interval [CI] 0.726, 0.920) and an accuracy of 0.80 (95% CI 0.70, 0.88). The AUCs of prediction models for beta‐blockers, tricyclic antidepressants, topiramate, verapamil, gabapentin, and onabotulinumtoxinA were: 0.664 (95% CI 0.579, 0.745), 0.611 (95% CI 0.562, 0.682), 0.605 (95% CI 0.520, 0.688), 0.673 (95% CI 0.569, 0.724), 0.628 (0.533, 0.661), and 0.581 (95% CI 0.550, 0.632), respectively. Baseline monthly headache days, age, body mass index (BMI), duration of migraine attacks, responses to previous medication trials, cranial autonomic symptoms, family history of headache, and migraine attack triggers were among the most important variables across all models. A variable could have different contributions; for example, lower BMI predicts responsiveness to CGRP mAbs and beta‐blockers, while higher BMI predicts responsiveness to onabotulinumtoxinA, topiramate, and gabapentin. Conclusion: We developed an accurate prediction model for CGRP mAbs treatment response, leveraging detailed migraine features gathered from a headache questionnaire before starting treatment. Employing the same methods, the model performances for other medications were less impressive, though similar to the machine learning models reported in the literature for other diseases. This may be due to CGRP mAbs being migraine‐specific. Incorporating medical comorbidities, genomic, and imaging factors might enhance the model performance. We demonstrated that migraine characteristics are important in predicting treatment responses and identified the most crucial predictors for each of the seven types of preventive medications. Our results suggest that precision migraine treatment is feasible. Plain Language Summary: Currently, there is no way to predict whether preventive medications, which are medications that may reduce the frequency and severity of headaches, will be helpful to all patients. We used novel artificial intelligence techniques and developed effective tools that can predict how a patient responds to seven different types of migraine preventive medications before the medication is started. We also found that the ways in which patients describe their headache and the types of symptoms they have is important to predict whether the medication will work. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) stands as one of the serious psychiatric conditions that detrimentally affect patients' quality of life and leads to a significant part of disability worldwide. Due to the limited understanding of the basic molecular mechanisms of depression and antidepressant medications, a clear understanding of the onset and development of MDD is unavailable. This study aims to figure out the pivotal genes and pathways implicated in the MDD development and identify medications that can potentially improve MDD treatment based on their relation with the key genes. Method: Symbols of human coding genes were retrieved from the HUGO Gene Nomenclature Committee database. These symbols were then queried for MDD-related associations using a Python script in PubMed. Subsequently, genes with two or more related articles to MDD were selected. A union of our search data and MDD-related genes in the DisGeNET database was found. The gene interaction network was generated and analyzed utilizing the STRING and Cytoscape, respectively. Finally, a drug-gene network was constructed and medications that can affect multiple genes were selected. Results: The union of our search data and DisGeNET data contained 1734 genes. Based on network analysis, TNF, IL1B, IL6, STAT1, and STAT3 were identified as the key genes in the MDD pathogenesis. Eleven drugs that affect more than one gene were detected through a drug-gene network. These medications include Acitretin, Adalimumab, Alteplase, Cisplatin, Digoxin, Etanercept, Infliximab, Insulin, Omeprazole, Pentoxifylline, and Rabeprazole. Conclusion: In summary, our findings identified five genes as key genes in MDD development, as well as medications related to key genes. This study provides a new vision of the pathogenesis and treatment of MDD. However, further experimental and clinical studies are necessary. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the proportion of Australians dispensed psychotropic medications between 2013 and 2022 according to their age. Methods: Services Australia provided a de-identified 10% random Pharmaceutical Benefits Scheme sample that allowed us to determine, for each year, the proportion of Australians dispensed at least one script for antipsychotics, antidepressants, anxiolytics, or hypnotics. The classification of medications followed Anatomical Therapeutic Chemical coding. Participants were stratified into 10-year age groups from 0–9 to ⩾90 years, and sex was coded as male/female. We retrieved population numbers from the Australian Bureau of Statistics. Results: The number of records per year ranged from 1,540,520 to 1,746,402, and 54.10% were for females. A greater proportion of older adults, particularly those aged ⩾70 years, were dispensed antipsychotics, antidepressants, anxiolytics and hypnotics than any other age group. The proportion of people who dispensed antipsychotics, anxiolytics and hypnotics declined between 2013 and 2022 but increased for antidepressants, most markedly for adolescents and young adults. Females were more frequently dispensed antidepressants, anxiolytics and hypnotics than males, but males were more frequently dispensed antipsychotics than females, albeit not in later life. Conclusion: Older age groups and females are the most frequent recipients of psychotropic medications dispensed in Australia. [ABSTRACT FROM AUTHOR]

Ketamine is a restricted and regulated medication in Australia and New Zealand, which has implications when considering treatment for patients with treatment-resistant depression and a history of illicit drug use, abuse or dependence. Regulations governing prescription of ketamine for treatment-resistant depression vary between jurisdictions in Australia and New Zealand, though most restrict use in those with drug dependence. There is substantial variation in definitions of drug dependence used in each jurisdiction, and between the legal and clinical definitions, with the latter specified in the current International Classification of Diseases, Eleventh Revision and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This paper reviews the literature assessing the risk of ketamine misuse and dependence in patients with a history of illicit drug use, abuse or dependence and presents recommendations for psychiatrists who prescribe ketamine in such patients with treatment-resistant depression. [ABSTRACT FROM AUTHOR]

This study endeavors to deepen our understanding of the subject matter by exploring, within a real-world sample, the impact of menopausal status on the antidepressant treatments response. The whole sample included a total of 447 patients, 156 male and 291 female, 110 pre-menopause and 181 post-menopause. In our sample post-menopause women showed a worse response to antidepressants than pre-menopause women (p = 0.006), and this difference seems to be unrelated to age or brain aging. [ABSTRACT FROM AUTHOR]

Purpose: Perinatal mood disorders affect both parents, impacting their children negatively. Little is known on the association between parental perinatal mood disorders and pediatric outcomes in Japan considering relevant covariates. Our objective was to investigate the association between paternal and maternal perinatal mood disorders and adverse physical and psychological child outcomes by the age of 36 months, adjusting for covariates such as the child's sex, age of parent at child's birth, perinatal mood disorders of the other parent, and perinatal antidepressant use. Methods: We identified parents in the JMDC Claims Database in Japan from 2012 to 2020. Perinatal mood disorders were defined using International Classification of Diseases, 10th codes for mood disorders during the perinatal period combined with psychiatric treatment codes. We evaluated the association between parental perinatal mood disorders and pediatric adverse outcomes by the age of 36 months using Cox proportional hazard models adjusted for the covariates. Results: Of the 116,423 father-mother-child triads, 2.8% of fathers and 2.3% of mothers had perinatal mood disorders. Paternal perinatal mood disorders were not significantly associated with adverse child outcomes. After adjusting for paternal perinatal mood disorders and antidepressant use, maternal perinatal mood disorders were associated with delayed motor development, language development disorders, autism spectrum disorders, and behavioral and emotional disorders (adjusted hazard ratio [95% confidence interval]: 1.65 [1.01–2.69], 2.26 [1.36–3.75], 4.16 [2.64–6.55], and 6.12 [1.35–27.81], respectively). Conclusions: Paternal perinatal mood disorders were not associated with adverse child outcomes in this population. Maternal perinatal mood disorders were associated with multiple child outcomes. [ABSTRACT FROM AUTHOR]

Available data shows associations between chronotype, circadian rhythms, sleep quality and fibromyalgia (FM) presentation. However, no studies have explored links between the chronobiological variables and effectiveness of pharmacotherapy. We aimed to assess the chronotypes, circadian rhythms, sleep-wake cycle and sleep quality in FM and their links to treatment response to serotonin and noradrenalin reuptake inhibitors (SNRI). 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-]) and 30 healthy controls participated. Subjects were assessed by physician and with questionnaire tools: Composite Scale of Morningness, Biological Rhythms Interview of Assessment in Neuropsychiatry, Sleep-Wake Pattern Assessment Questionnaire, Pittsburgh Sleep Quality Index and Fibromyalgia Impact Questionnaire. ANOVA analysis and simple logistic regressions were used to examine the relationships between chronological variables and response to SNRI. FM T[-] vs. FM T[+] presented lower morning affect (11.50[95%CI 9.96-13.04] vs. 14.00[95%CI 12.42-15.57];p=0.04), anytime wakeability (2.27[95%CI 1.4-3.13] vs. 4.03[95%CI 2.99-5.08];p=0.013) worse overall (11.40[95%CI 9.92-12.88] vs. 7.97[95%CI 6.75-9.19];p=0.002) and subjective (1.70[95%CI 1.30-2.01] vs. 1.17[95%CI 0.94-1.39];p=0.008) sleep quality, higher circadian rhythm disruptions (55.47[95%CI 52.32-58.62] vs. 44.97[95%CI 41.31-48.62];p<0.001), sleep disturbances (1.63[95%CI 1.38-1.68] vs. 1.30[95%CI 1.1-1.5];p=0.04), sleeping-medication use (1.80[95%CI 1.27-2.32] vs. 0.70[95%CI 0.28-1.12];p=0.003). Levels of morningness (AIC=82.91,OR=0.93,p=0.05), morning affect (AIC=81.901,OR=0.86,p=0.03) diurnal dysrhythmia (AIC=69.566,OR=1.14,p<0.001), anytime wakeability (AIC=80.307,OR=0.76,p=0.015), overall sleep quality (AIC=74.665, OR=1.31,p=0.002) subjective sleep quality (AIC=79.353, OR=2.832,p=0.01) and disturbances (AIC=82.669,OR=2.54,p=0.043), sleep medication use (AIC=77.017, OR=1.9,p=0.003) and daytime disfunction (AIC=82.908, OR=1.971,p=0.049) were predictors of non-response to SNRI. Chronobiological variables vary between FM T[+] and FM T[-] and are predictors of non-response to SNRI. [ABSTRACT FROM AUTHOR]

A systematic review and meta‐analysis encompassing 79 studies has found that around one‐third of patients who discontinue antidepressant medication will experience adverse symptoms, but only around 1 in 30 will experience severe discontinuation symptoms. An analysis of individual antidepressants found that imipramine, desvenlafaxine, and venlafaxine were associated with the highest incidence of discontinuation symptoms. Results were published online June 5, 2024, in Lancet Psychiatry. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the importance of a multidimensional view of disparities in quality of antidepressant medication management (AMM), as well as discriminating "within‐facility" disparities from disparities that exist between facilities. Data Sources and Study Setting: We used data from the Veterans Health Administration's (VA) Corporate Data Warehouse (CDW) which contains clinical and administrative data from VA facilities nationally. Study Design: CDW data were used to measure five indicators of AMM quality, including the HEDIS Effective Acute‐Phase and Effective Continuation‐Phase measures. Mixed effects regression models were used to examine differences in quality indicators between racial/ethnic groups, controlling for other demographic and clinical factors. An adaptation of the Kitagawa‐Blinder‐Oaxaca (KBO) method was used to decompose mean differences in treatment quality between racial and ethnic groups into within‐ and between‐facility effects. Data Extraction Methods: Demographic, clinical, and health service utilization data were extracted for patients in fiscal year 2017 with a diagnosis of depression and a new start of an antidepressant medication. Principal Findings: The decomposition of the overall differences between White and Black patients on receiving an initial 90‐day prescription (46.7% vs. 32.7%), Effective Acute‐Phase (79.7% vs. 66.8%), and Effective Continuation‐Phase (64.0% vs. 49.6%) HEDIS measures revealed that most of the overall effects were "within‐facility," meaning that Black patients are less likely to meet these measures regardless of where they are treated. Although the overall magnitude of disparities between White and Hispanic patients on these three measures was very similar (46.7% vs. 32.7%; 79.7% vs. 69.2%; 64.0% vs. 53.6%), the differences were more attributable to Hispanic patients being treated in facilities with overall lower performance on these measures. Conclusions: Discriminating within‐ and between‐facility disparities and taking a multidimensional view of quality are essential to informing efforts to address disparities in AMM quality. [ABSTRACT FROM AUTHOR]

Objectives. To examine trends in overdose deaths by intent and drug category to better understand the recent decrease in overdose suicides amid the overdose epidemic. Methods. We examined trends in rates of overdose deaths by intent (unintentional, suicide, or undetermined) across 9 drug categories from 1999 to 2022 using US National Vital Statistics System mortality data. Results. Unintentional overdoses involving synthetic opioids, polydrug toxicity involving synthetic opioids, psychostimulants, and cocaine increased exponentially with annual percentage changes ranging from 15.0% to 104.9% during 2010 to 2022. The death rates also increased for suicides involving these drugs, especially for psychostimulants (annual percentage change = 12.9% for 2010–2022; P <.001). However, these drugs accounted for relatively small percentages of overdose suicides. The leading drug categories among suicides were antidepressants, prescription opioids, and benzodiazepines, though these deaths have decreased or leveled off in recent years. Conclusions. Different drugs commonly involved in suicides and unintentional overdoses may contribute to their divergent trends. Public Health Implications. Amid the overdose epidemic, safe storage of medications remains a crucial strategy to prevent overdose suicides. The large increases in suicides involving psychostimulants warrant monitoring. (Am J Public Health. 2024;114(10):1081–1085. https://doi.org/10.2105/AJPH.2024.307745) [ABSTRACT FROM AUTHOR]

Background: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram. Aims: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness—assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice. Method: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent‐related") confounding by indication. Results: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91–1.05) for citalopram and 1.21 (95% CI = 1.10–1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82–1.18). The results of the analyses of suicide were inconclusive, due to few outcome events. Conclusions: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent‐related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation. [ABSTRACT FROM AUTHOR]

Approximately 30 % of persons with Major Depressive Disorder (MDD) inadequately respond to conventional antidepressants. Kappa opioid receptor (KOR) antagonists, aticaprant and navacaprant, are in development as treatments for MDD. Herein, we aim to comprehensively evaluate the safety, efficacy and pharmacology of aticaprant and navacaprant for MDD. We performed a systematic review of primary research investigating aticaprant and navacaprant on PubMed, OVID, and Scopus databases from inception to April 2024. Studies that reported on the pharmacological profile and/or safety and efficacy of aticaprant and navacaprant were included. Navacaprant monotherapy and aticaprant adjunctive therapy are in development for MDD. Navacaprant exhibits 300-fold selectivity for the KOR compared to the mu-opioid receptor, while aticaprant exhibits 30-fold selectivity. At clinically-relevant doses, navacaprant and aticaprant occupy 87–95 % and 73–94 % of KORs, respectively. Clinical trials of the foregoing agents (navacaprant as monotherapy and actiprant as adjunctive therapy) reported significant improvement in depressive symptoms and may clinically benefit measures of anhedonia. Both agents appear well-tolerated, with most adverse events mild and no known safety concerns. Aticaprant and navacaprant treatment for MDD are in early stages of clinical trials and results from Phase 3 pivotal trials are not yet available. Kappa opioid receptor antagonists may serve as mechanistically-novel treatments for MDD and persons who inadequately respond to index conventional antidepressants. Anhedonia is debilitating and insufficiently treated with conventional antidepressants. Future research vistas should establish the efficacy and safety of KORAs in phase 3 studies in both acute and maintenance paradigms. • Aticaprant adjunctive therapy and navacaprant monotherapy are in development for MDD. • Navacaprant has 300-fold selectivity for kappa opioid receptors over mu and delta. • Aticaprant has 30-fold selectivity for kappa opioid receptors over mu and delta. • Aticaprant and navacaprant reduced depressive symptoms in persons with MDD. • Treatment-emergent adverse events were mild in severity and tolerable. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. The study was registered with clinicaltrials.gov (NCT04433767). • Augmentation with open-label transdermal nicotine patches improved depression severity and secondary affective symptoms. • Nicotine administration also improved executive function, specifically cognitive control. • Nicotine patches were safe and well tolerated in older depressed nonsmoking participants. • Rigorous blinded, randomized trials are needed to definitively demonstrate efficacy. [ABSTRACT FROM AUTHOR]

Population-based surveys suggest that low socioeconomic status (SES) is associated with higher prevalence of depressive symptoms, while their healthcare utilization is not necessarily higher. To investigate the association between neighborhood socioeconomic status (NSES) and healthcare utilization among individuals diagnosed with major depressive disorder (MDD). This was a retrospective longitudinal study of all adults with a first MDD diagnosis within primary care during 2010–2018. NSES was defined by the household area of residence using the Mosaic™ classification. Outcomes were AD (antidepressants) (N06A) dispensation and psychiatric outpatient visit, both of which are outlined as options in depression guidelines. Cox multivariable regression was used for the time to event analyses. A total of 117,193 individuals were included, of which 87,499 (75 %) were dispensed an AD and 35,989 (31 %) had a recorded psychiatric outpatient visit. Low NSES was associated with lower rate of AD dispensation in the first-year post-diagnosis (HR: 0.95, 95 % CI: 0.93–0.96, p < 0.001) and higher rate of psychiatric visit (HR: 1.10, 95 % CI: 1.07–1.12, p < 0.001) compared with high NSES. Data sources have high coverage. A minority of psychiatric care provided by non-publicly financed providers was not included. It was not possible to adjust for depression severity. Socioeconomic status as measured by the neighborhood of residency was associated with AD dispensation and psychiatric outpatient visit in MDD, also in a healthcare system with virtually free access. This is of relevance for clinical practice, considering the focus on equity of care and the increase in depression prevalence worldwide. • A total of 75 % were dispensed an AD (antidepressant) while 31 % had a specialist psychiatric outpatient visit post-diagnosis. • AD dispensation • The low NSES group had 5 % lower rate of AD compared with the high NSES group in the first-year post-diagnosis. • Females had 7 % lower rate of AD compared with males. Older age was associated with 54 % higher rate of AD compared with younger. • Outpatient psychiatric visit • The low NSES was associated with 10 % higher rate of psychiatric outpatient visit post-diagnosis compared with high NSES. • Being female and of older age was associated with 18 % and 60 % lower rate of psychiatric visit respectively. • Socioeconomic status, measured by neighborhood of residency was associated with AD and psychiatric outpatient visit in MDD. [ABSTRACT FROM AUTHOR]

Objective: As part of the Geriatric Emergency Department (ED) Guidelines 2.0 project, we conducted a systematic review to find risk factors or risk stratification approaches that can be used to identify subsets of older adults who may benefit from targeted ED delirium screening. Methods: An electronic search strategy was developed with a medical librarian, conducted in April 2021 and November 2022. Full‐text studies of patients ≥65 years assessed for prevalent delirium in the ED were included. Risk of bias was assessed using the McMaster University Clarity Group tool. Outcomes measures pertained to the risk stratification method used. Due to heterogeneity of patient populations, risk stratification methods, and outcomes, a meta‐analysis was not conducted. Results: Our search yielded 1878 unique citations, of which 13 were included. Six studies developed a novel delirium risk score with or without evaluation of specific risk factors, six studies evaluated specific risk factors only, and one study evaluated an existing nondelirium risk score for association with delirium. The most common risk factor was history of dementia, with odds ratios ranging from 3.3 (95% confidence interval [CI] 1.2–8.9) to 18.33 (95% CI 8.08–43.64). Other risk factors that were consistently associated with increased risk of delirium included older age, use of certain medications (such as antipsychotics, antidepressants, and opioids, among others), and functional impairments. Of the studies that developed novel risk scores, the reported area under the curve ranged from 0.77 to 0.90. Only two studies reported potential impact of the risk stratification tool on screening burden. Conclusions: There is significant heterogeneity, but results suggest that factors such as dementia, age over 75, and functional impairments should be used to identify older adults who are at highest risk for ED delirium. No studies evaluated implementation of a risk stratification method for delirium screening or evaluated patient‐oriented outcomes. [ABSTRACT FROM AUTHOR]

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Introduction: Antidepressants and menopause are risk factors which are independently associated with an increased risk of fractures. This review aims to investigate the risk of fragility fractures in women aged 40 and older and prescribed antidepressants. Methods: A literature search was conducted using PubMed, Ovid Embase, Ovid PsychINFO, Web of Science, and Scopus from inception to 1 June 2024. Relevant citations were identified and screened against our inclusion/exclusion criteria. The study population comprised women over 40 years. The risk of fragility fractures was compared between users and non-users of antidepressants. Risk of bias assessment was carried out using the ROBINS-I tool. A meta-analysis of cohort studies was performed to assess fracture risk associated with prescribing of any antidepressant agents, and SSRIs specifically. Results: Of the 3,676 articles retrieved, five observational studies were found eligible for inclusion (n = 1,240,354). In a meta-analysis of 4 studies, an increased risk of fractures in women was associated with the prescribing of antidepressants (HR = 1.62, 95% CI: 1.15–2.28; I2 = 96.50%) and SSRIs in particular (HR = 1.36, 95% CI: 1.20–1.55; I2 = 40.32%). Conclusions: Findings from this review suggest that prescribing of antidepressants is associated with an increased risk of fractures in women aged 40 and older. Substantial heterogeneity between studies may have affected the results of the meta-analysis. [ABSTRACT FROM AUTHOR]

Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6‐dependent opioids while on CYP2D6‐inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6‐dependent opioids utilizing electronic health records data from the University of Florida Health (2015–2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine‐treated patients exposed to CYP2D6‐inhibitor antidepressants (n = 7,043) had a higher crude rate of pain‐related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6‐inhibitor antidepressant‐exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27–2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control. [ABSTRACT FROM AUTHOR]

Objective: Using benzodiazepines and certain antidepressants is associated with an increased risk of motor vehicle crashes due to impaired driving skills. Hence, several countries prohibit people who use these drugs from driving. Traffic regulations for driving under the influence of these drugs are, however, largely based on single-dose studies with healthy participants. The effects of drugs on chronic users may be different because of potential development of tolerance or by adapting behavior. In this study, we test the effects of anti-depressants, hypnotics, or anxiolytics use on driving performance in patients who use these drugs for different durations and compare the effects to healthy controls' performance. Methods: Sixty-six healthy controls and 82 medication users were recruited to perform four drives in a driving simulator. Patients were divided into groups that used anti-depressants, hypnotics, or anxiolytics, for shorter or longer than 3 years (i.e. LT3− or LT3+, respectively). The minimum term of use was 6 months. Driving behavior was measured in terms of longitudinal and lateral control (speed variability and Standard Deviation of Lateral Position: SDLP), brake reaction time, and time headway. Impaired driving performance was defined as performing similar to driving with a Blood Alcohol Concentration of 0.5‰ or higher, determined by means of non-inferiority analyses. Results: Reaction time analyses revealed inconclusive findings in all groups. No significant performance differences between matched healthy controls, LT3− (n = 2), and LT3+ (n = 8) anxiolytics users were found. LT3+ antidepressants users (n = 12) did not perform inferior to their matched controls in terms of SDLP. LT3− hypnotics users (n = 6) showed more speed variability than their matched healthy controls, while this effect was not found for the LT3+ group (n = 14): the latter did not perform inferior to the healthy controls. Regarding Time Headway, no conclusions about the LT3− hypnotics group could be drawn, while the LT3+ group did not perform inferior compared to the control group. Conclusions: The small number of anxiolytics users prohibits drawing conclusions about clinical relevance. Although many outcomes were inconclusive, there is evidence that some elements of complex driving performance may not be impaired (anymore) after using antidepressants or hypnotics longer than 3 years. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions Antidepressants may lead to a series of sexual adverse effects (SAEs), among which ejaculation dysfunction (EjD) is often overlooked by clinicians. The purpose of the present network meta‐analysis was to assist drug adjustment by comparing and ranking the incidence of EjD among various antidepressants.Relevant studies were retrieved from PubMed, Embase, Scopus, Web of Science, ClinicalTrials.gov, and other additional records. Eligible randomized controlled trials (RCTs) assessed the rate of EjD in patients with major depressive disorder (MDD) and anxiety disorder after taking anti‐depressants. The incidences of EjD, erectile dysfunction (ED), decreased libido (DL), adverse events (AE), withdrawal due to adverse events (WDAE) and withdrawal due to lack of efficacy (WDLE) were pooled using odds ratio (OR) with their 95% confidence intervals (CI). The values of surface under the cumulative ranking curve (SUCRA) helped to rank the risk of each outcome in different antidepressants.Thirty RCTs comprising 18,157 patients were included. Results of all node‐splitting analysis demonstrated no statistical inconsistency (all P > 0.05). Clomipramine (OR 42.11, 95% CI [9.90, 179.08]), WS5570 (OR 28.99, 95% CI [1.48, 568.97]) and paroxetine (OR 18.63, 95% CI [9.33, 37.23]) had significant risk of EjD comparing to placebo. Additionally, duloxetine (OR 7.37, 95% CI [2.61, 20.78]), clomipramine (OR 5.29, 95% CI [1.72, 16.25]), paroxetine (OR 3.75, 95% CI [1.37, 10.26]) and escitalopram (OR 3.04, 95% CI [1.20, 7.71]) presented higher risk of ED comparing to placebo. Agomelatine, levomilnacipran, vortioxetine, trazodone, vilazodone, fluvoxamine and imipramine exhibited similar incidence of EjD with placebo (all P > 0.05). Besides, trazodone, vilazodone and vortioxetine had the top‐five SUCRA values in each of SAEs (EjD, ED and DL), and agomelatine might be alternative in EjD and DL. Considering about AE, WDAE and WDLE, vilazodone appeared to offer more satisfactory performance across all these aspects.For patients undergoing SAEs following the administration of antidepressants, trazodone, vortioxetine, vilazodone and agomelatine are alternative antidepressants. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Older‐age bipolar disorder (OABD) is commonly defined as bipolar disorder in individuals aged 60 or more. There have been no studies to examine temporal trends in the pharmacological treatment of OABD. We aimed to investigate prescription changes among OABD patients discharged from two public mental hospitals in Taiwan from 2006 to 2019.OABD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 1072), entered the analysis. Prescribed drugs at discharge, including mood stabilisers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second‐ and first‐generation antipsychotics (SGAs and FGAs)), and antidepressants, were investigated. Complex polypharmacy was defined as the use of three or more agents among the prescribed drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran‐Armitage Trend test.The most commonly prescribed drugs were SGAs (72.0%), followed by valproate (48.4%) and antidepressants (21.7%). The prescription rates of SGAs, antidepressants, antidepressants without mood stabilisers, and complex polypharmacy significantly increased over time, whereas the prescription rates of mood stabilisers, lithium, FGAs, and antidepressants plus mood stabilisers significantly decreased.Prescribing patterns changed remarkably for OABD patients over a 14‐year period. The decreased use of lithium and increased use of antidepressants did not reflect bipolar treatment guidelines. Future research should examine whether such prescribing patterns are associated with adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: In 2019, coronavirus disease 2019 (COVID-19) emerged in China, spreading globally with significant impacts in Japan, including the Delta and Omicron variants. The research identified risk factors such as age, chronic diseases, and lifestyle choices, emphasizing the need for further study on the association between underlying health conditions, treatments, and COVID-19 severity in Japan. Methods: This study used a nationwide medical database to analyze the association between COVID-19 underlying conditions and pharmacological interventions to identify risk factors for disease severity. We examined the Japanese COVID-19 dataset from Medical Data Vision, selecting patients diagnosed with COVID-19 between January 2020 and December 2022. Logistic regression was used to calculate the odds ratios (ORs) for intensive care unit treatment- or ventilator use-related risk factors. Results: Among 650,317 patients (mean age: 52.1 ± 20.9 years; male individuals: 324,127; female individuals: 326,190), factors that significantly increased the severe disease risk (OR [95% confidence interval]) included age > 65 years (1.31 [1.27–1.36]), hypertension (1.34 [1.28–1.41]), cardiovascular disease (1.74 [1.67–1.81]), and use of beta-blockers (2.09 [2.00–2.17]), calcium blockers (1.97 [1.89–2.06]), angiotensin-converting enzyme inhibitors (1.41 [1.33–1.49]), low-dose aspirin (1.38 [1.32–1.45]), and insulin (7.14 [6.87–7.43]). Conversely, factors that reduced the severe disease risk included female sex and the use of sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists, and alpha-glucosidase inhibitors. Conclusions: Patients using cardiovascular medications faced a higher risk, whereas those receiving diabetes treatment had a lower risk. Appropriate pharmacotherapy and risk factor identification can aid in the prevention of severe COVID-19. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusions\nKEY POINTSTherapeutic drug monitoring (TDM) is an important tool for treatment optimisation. Its usefulness has recently been demonstrated for some first-line antidepressants; however, few studies have been reported on the relationship between blood levels of mirtazapine and its antidepressant effects. The aim of this study was to investigate the association between blood concentration of mirtazapine and antidepressant response.59 outpatients treated with mirtazapine for depression were recruited and followed up for three months in a naturalistic setting. Hamilton Depression Rating Scale-21 (HAMD-21) was administered at baseline, month 1, and month 3 to assess antidepressant response. Mirtazapine serum concentration was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between serum concentration of mirtazapine and antidepressant response.Our results showed no overall association between serum concentration of mirtazapine and symptom improvement at month 1 and month 3. A marginally significantly higher serum concentration of mirtazapine was found in responders vs non-responders at month 3.The study suggests that serum concentration of mirtazapine is not strongly associated with the antidepressant efficacy of mirtazapine. This is probably attributed to its pharmacodynamic profile, even though higher blood levels seem to be marginally more effective.Mirtazapine plasma levels association with response is mild and do not follow the same curve of other antidepressantsMirtazapine higher plasma levels may show some benefit in a subgroup of patientsTherapeutic drug monitoring may help during antidepressant treatment [ABSTRACT FROM AUTHOR]

Background: Neuropathic pain (NP) is a chronic and disabling condition, caused by a lesion or disease of the somatosensory nervous system, characterized by a systemic inflammatory state. Signs and associated symptoms are rarely recognized, and response to usual analgesic drugs is poor. Antidepressant drugs are first-line agents for the treatment of NP. This narrative review aims to summarize the role of antidepressant drugs in treating NP and their mechanism of action, focusing on the effects on inflammatory cytokines. Main text. Peripheral nerve injury leads to a local inflammatory response and to the disruption of the blood-medullary barrier, allowing the influx of peripheral immune cells into the central nervous system. Antidepressants have antinociceptive effects because they recruit long-term neuronal plasticity. Amitriptyline modulates the inflammatory response due to the reduction of the mRNA of pro-inflammatory cytokines acting as an adenosine agonist and leading to the activation of the A3AR receptor. Through toll-like receptors, local inflammation determines the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) that drives and stimulates the hyperflammation in NP. Nortriptyline has an important antiallodynic effect in NP as it determines the recruitment of norepinephrine in the dorsal root ganglia. By modulating the β2-adrenoreceptors expressed by non-neuronal satellite cells, it inhibits the local production of TNF-α and determines a reduction of NP symptoms. Following the administration of antidepressants, there is a reduction in the production of TNF-α in the brain which in turn transforms the function of the α2-adrenergic receptor from an inhibitor to an activator of the release of norepinephrine. This is important to prevent the development of chronic pain. Conclusion: Inflammatory cytokines are the main players in a bidirectional communication between the central and peripheral nervous system and the immune system in NP. Antidepressants have an important role in NP. Further research should explore the interaction between neuroinflammation in NP, the effects of antidepressants and the clinical relevance of this interaction. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 μL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 μg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method's efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Agitated depression, also known as melancholia agitata, is a variant of depression characterized by severe symptoms of psychomotor agitation, inner unrest, anxiety, restlessness, prominent vegetative symptoms, and a high risk of suicide. This form of depression is reported to worsen with antidepressants and potentially improve with the use of ECT, lithium, antiepileptics, antipsychotics, and benzodiazepines. We describe a case of a 73‐year‐old female with a prior history of depression and generalized anxiety disorder who was maintained on flurazepam for 44 years and was admitted for severe depression with psychomotor agitation, prominent vegetative symptoms, thought perseveration, indecisiveness, and psychotic features that emerged following the discontinuation of flurazepam. Symptoms did not resolve with the use of alternative benzodiazepines such as nitrazepam and temazepam and further worsened with the use of several antidepressants. She finally had a complete resolution of these symptoms with a combination of alprazolam, zopiclone, and olanzapine. This case provides insight into this unique variant of depression and the role of GABA agonists in its pathology and management. [ABSTRACT FROM AUTHOR]