OBJECTIVE: A rise in affective and anxiety disorders and in antidepressant (AD) treatment during the COVID-19 pandemic has been extensively described, but few studies were provided at the individual level, further considering COVID-19 severity and vaccination status.
METHODS: Case-control study evaluating the association between the new use of ADs and a previous COVID-19 infection, in Friuli Venezia Giulia Region, Italy, from March 1, 2020, to July 19, 2022. Multiple conditional logistic regressions assess the association between a new AD use and a COVID-19 infection previous to the index date, stratified by gender, age and anti-COVID-19 vaccination status. Odds Ratios (OR) and 95% confidence intervals were reported.
RESULTS: COVID-19 was associated with AD treatment after the infection. The disease severity was positively associated with a growing risk of being dispensed an AD, with the highest risk in unvaccinated subjects previously hospitalised in ICU (OR = 28.77). The risk of using ADs after COVID-19 infection was higher in unvaccinated subjects aged 65 years and older, both females and males. The association between COVID-19 infection and AD dispensation in vaccinated subjects was not significant, with the exception of females aged 65 years and over.
CONCLUSIONS: Anti-COVID-19 vaccination, especially among the elderly, might prevent post-COVID AD treatment. Clinicians should be aware that COVID-19 patients requiring hospitalisation are more likely to experience these symptoms, given their higher risk of being dispensed ADs. Future studies may benefit by analysing the incidence of both mental disorders and psychotropic treatment in post-COVID patients, considering socioeconomic factors and vaccination status.

Depressive disorders are one of the most common mental disorders globally and progress in treating these disorders has been hampered, in part, by a lack of suitable nonclinical efficacy tests. Two common tests used in nonclinical efficacy studies of antidepressants-the forced swim test (FST) and tail suspension test (TST)-have come under criticism in recent years for their inconsistency and lack of validity, yet they continue to be used in the pharmaceutical industry. In this review, we provide a rationale for why international pharmaceutical regulatory and guidance agencies should begin issuing direction on methods for non-clinical efficacy testing that traditionally use the FST and TST, particularly considering that some regulators, such as those in the U.S. and E.U., allow the authorization of clinical trials to proceed without requiring tests in animals. The area of antidepressant drug discovery represents an important opportunity for reducing the attrition of psychiatric drugs, harmonizing regulatory requirements, and reducing animal use. Specific recommendations for the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) have been provided.

Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called \"therapy-resistant depression\". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a \"patient fingerprint\", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.

This review focus on the terpenoids as potential therapeutic agents for depression and anxiety disorders, which naturally found in a variety of plants and exhibit a wide range of biological activities. Among the terpenoids discussed in this review are α-pinene, β-caryophyllene, α-phellandrene, limonene, β-linalool, 1, 8-cineole, β-pinene, caryophyllene oxide, p-cymene, and eugenol. All of these compounds have been studied extensively regarding their pharmacological properties, such as neuroprotective effect, anti-inflammation, antibacterial, regulation of neurotransmitters and antioxidant effect. Preclinical evidence are reviewed to highlight their diverse mechanisms of action and therapeutic potential to support antidepressant and anxiolytic properties. Additionally, challenges and future directions are also discussed to emphasize therapeutic utility of terpenoids for mental health disorders. Overall, this review provides a promising role of terpenoids as novel therapeutic agents for depression and anxiety, with potential implications for the development of more effective and well-tolerated treatments in the field of psychopharmacology.

Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side effects. In this regard, the search for and development of new antidepressant agents remains an urgent task. In this review, we discuss the current available evidence indicating that G protein-coupled trace amine-associated receptors (TAARs) might represent new targets for depression treatment. The most frequently studied receptor TAAR1 has already been investigated in the treatment of schizophrenia, demonstrating antidepressant and anxiolytic properties. In fact, the TAAR1 agonist Ulotaront is currently undergoing phase 2/3 clinical trials testing its safety and efficacy in the treatment of major depressive disorder and generalized anxiety disorder. Other members of the TAAR family (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) are not only involved in the innate olfaction of volatile amines, but are also expressed in the limbic brain areas. Furthermore, animal studies have shown that TAAR2 and TAAR5 regulate emotional behaviors and thus may hold promise as potential antidepressant targets. Of particular interest is their connection with the dopamine and serotonin systems of the brain and their involvement in the regulation of adult neurogenesis, known to be affected by the antidepressant drugs currently in use. Further non-clinical and clinical studies are necessary to validate TAAR1 (and potentially other TAARs) as novel therapeutic targets for the treatment of depression.

The incidence of major depressive disorder (MDD) after heart transplantation is high; however, there are no reports on treatment options when antidepressant therapy fails to improve the condition. We herein report on the case of a woman with MDD after heart transplantation who partially improved with antidepressant treatment but continued to have a loss of appetite. Augmentation treatment with aripiprazole improved her appetite, and her MDD went into remission. When antidepressant treatment is not sufficiently effective for MDD after heart transplantation, augmentation treatment with antipsychotics, such as aripiprazole, should be considered.

The increasing prevalence of depression is a major societal burden. The etiology of depression involves multiple mechanisms. Thus, the outcomes of the currently used treatment for depression are suboptimal. The anti-depression effects of traditional Chinese medicine (TCM) formulations have piqued the interest of the scientific community owing to their multi-ingredient, multi-target, and multi-link characteristics. According to the TCM theory, the functioning of the kidney is intricately linked to that of the brain. Clinical observations have indicated the therapeutic potential of the kidney-tonifying formula Erxian Decoction (EXD) in depression. This review aimed to comprehensively search various databases to summarize the anti-depression effects of EXD, explore the underlying material basis and mechanisms, and offer new suggestions and methods for the clinical treatment of depression. The clinical and preclinical studies published before 31 August 2023, were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, and Wanfang Database. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical studies have demonstrated that EXD exhibits therapeutic properties in patients with menopausal depression, postpartum depression, and maintenance hemodialysis-associated depression. Meanwhile, preclinical studies have reported that EXD and its special chemical markers exert anti-depression effects by modulating monoamine neurotransmitter levels, inhibiting neuroinflammation, augmenting synaptic plasticity, exerting neuroprotective effects, regulating the hypothalamic-pituitary-adrenal axis, promoting neurogenesis, and altering cerebrospinal fluid composition. Thus, the anti-depression effects of EXD are mediated through multiple ingredients, targets, and links. However, further clinical and animal studies are needed to investigate the anti-depression effects of EXD and the underlying mechanisms and offer additional evidence and recommendations for its clinical application. Moreover, strategies must be developed to improve the quality control of EXD. This review provides an overview of EXD and guidance for future research direction.

Sheng-ma is recorded in the Compendium of Materia Medica and mainly originates from the rhizomes of Cimicifuga dahurica (Turcz.) Maxim. (CD), Cimicifuga heracleifolia Kom. and Cimicifuga foetida L. The alcoholic extract of Cimicifuga foetida L. (Brand name: Ximingting®) has been approved for the treatment of perimenopausal symptoms accompanying hot flash, depression and anxiety in China. However, there\'s no further study about the antidepressant-like effects of C. dahurica (CD). The aim of this study is to investigate the antidepressant-like effect of CD extracted by 75% ethanol and its possible mechanisms.The neuro-protective effects of CD on injured PC12 cells induced by corticosterone was measured firstly. Then, forced swim test (FST), tail suspension test (TST), reserpine-induced hypothermia, 5-hydroxytryptophan (5-HTP) induced head twitch response in mice and chronic unpredictable mild stress (CUMS) on sucrose preference tests were executed. Moreover, the potential mechanisms were explored by measuring levels of monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme A (MAO-A) activities in the brains of CUMS-exposed mice. Results showed that CD (60, 120 mg/kg) can significantly decreased the immobility period in FST and TST in mice without affecting locomotor activity. CD (30 mg/kg, 60 mg/kg, 120 mg/kg) could significantly counteracted reserpine-induced hypothermia and increased the number of head-twitches in 5-HTP induced head twitch response. It was also found that the monoamine neurotransmitter levels in the hippocampus and frontal cortex were significantly increased in 60 mg/kg and 120 mg/kg CD treated mice. In addition, CD (60 and 120 mg/kg) significantly inhibited MAO-A after 6-week CUMS exposure. CD can effectively produce an antidepressant-like effect, which involved with modulation of monoamine regulatory pathways.

BACKGROUND: 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.
OBJECTIVE: To investigate the association between neighborhood socioeconomic status (NSES) and healthcare utilization among individuals diagnosed with major depressive disorder (MDD).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.

Depression is a debilitating mental illness that has a significant impact on an individual\'s psychological, social, and physical life. Multiple factors, such as genetic factors and abnormalities in neurotransmitter levels, contribute to the development of depression. Monoamine oxidase inhibitors, tricyclic antidepressants, serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors, and atypical and new-generation antidepressants are well-known drug classes. SSRIs are the commonly prescribed antidepressant medications in the clinic. Genetic variations impacting serotonergic activity in people can influence susceptibility to diseases and response to antidepressant therapy. Gene polymorphisms related to 5-hydroxytryptamine (5-HT) signaling and subtypes of 5-HT receptors may play a role in the development of depression and the response to antidepressants. SSRIs binding to 5-HT reuptake transporters help relieve depression symptoms. Research has been conducted to identify a biomarker for detecting depressive disorders to identify new treatment targets and maybe offer novel therapy approaches. The pharmacological potentials of the piperazine-based compounds led researchers to design new piperazine derivatives and to examine their pharmacological activities. Structure-activity relationships indicated that the first aspect is the flexibility in the molecules, where a linker of typically a 2-4 carbon chain joins two aromatic sides, one of which is attached to a piperazine/phenylpiperazine/benzyl piperazine moiety. Newly investigated compounds having a piperazine core show a superior antidepressant effect compared to SSRIs in vitro/in vivo.