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In this study, a dispersive liquid–liquid microextraction along with a back-extraction step (DLLME-BE) has been developed for the determination of thre antidepressant drugs (citalopram, sertraline, and venlafaxine) in biological samples prior to HPLC-UV. Briefly, the method involved two main steps: first, a deep eutectic solvent (DES) composed of tetrabutylammonium bromide (TBABr as a dispersive agent) and 1-dodecanol (as the extraction solvent) was decomposed in an aqueous phase and led to in situ dispersion of the organic phase and extraction of analytes.. Second, Air-assisted liquid–liquid microextraction (AALLME) was applied to back-extract analytes into 50 µL of an aqueous acceptor phase while many interferences were not able to extract into the acceptor solution. By performing this developed extraction method, a high sample clean-up was achieved. The maximum efficiency of analytes was obtained based on the optimisation of the main parameters. Validation of the method indicated that the limits of detection (LODs) and limits of quantifications (LOQs) were in the range of 0.7–3.9 µg L−1 and 2.1–9.8 µg L−1 respectively. The extraction recoveries and enrichment factors of analytes were obtained to be in the range of 87.1–99.1% and 89–102, respectively. Finally, the method was utilised for extraction of three antidepressant drugs in water, human urine and plasma samples. [ABSTRACT FROM AUTHOR]

Aims: Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D. Methods: We conducted repeated annual cross‐sectional analysesof a population‐based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross‐sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype. Results: The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person‐years to 33.3 per 100 person‐years and from 2.8 per 100 person‐years to 4.7 per 100 person‐years, respectively). We observed this pattern for all drug subtypes except for first‐generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class. Conclusions: There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration. [ABSTRACT FROM AUTHOR]

We describe the design, synthesis and structure–activity relationship of a novel series of 1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with combined effects on the serotonin (5-HT1A) and dopamine (D2) receptors and the serotonin (5-HT), noradrenaline (NA), and dopamine (DA) transporters as multi-target directed ligands for the treatment of depression. All of the tested compounds demonstrated good affinity for the serotonin transporter (SERT). Among them, compounds 11 and 4 emerged as the lead candidates because of their promising pharmacological profile based on in vitro studies. Compound 11 displayed a high affinity for the 5-HT1A (Ki = 128.0 nM) and D2 (Ki = 51.0 nM) receptors, and the SERT (Ki = 9.2 nM) and DAT (Ki = 288.0 nM) transporters, whereas compound 4 exhibited the most desirable binding profile to SERT/NET/DAT among the series: Ki = 47.0 nM/167.0 nM/43% inhibition at 1 µM. These results suggest that compounds 4 and 11 represent templates for the future development of multi-target antidepressant drugs. [ABSTRACT FROM AUTHOR]

Abstract Identifying and managing the most critical side effects encourages patients to take medications regularly and adhere to the course of treatment. Therefore, priority should be given to the more important ones, among these side effects. However, the number of studies that make a priority examination is limited. There is a need for a new study that determines which of these effects are more priority to increase the quality of the treatment. Accordingly, this study aims to define the most important side effects of antidepressant drugs with a novel model. Quantum Spherical fuzzy M-SWARA technique is considered to compute the importance weights of the items. The main contribution of this study is that the most critical side effects can be understood for antidepressant drugs by establishing a novel decision-making model. The findings demonstrate that psychological side effects are defined as the most critical side effects of antidepressant drugs. Furthermore, physical side effects also play a key role in this condition. Side effects in antidepressant treatment have a great impact on the effectiveness of treatment and patient compliance.

Abstract 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.

Background We analysed the prevalence of depression under among pregnant women both in the immigrant and native populations in a Health Region of Spain, and evaluated the maternal factors associated with it. Methods We performed a retrospective observational cohort study in pregnant women in the Health Region of Lleida between 2012 and 2018. We analysed the following variables: age, body mass index (BMI), diabetes mellitus, hypertension, country of origin, and antidepressant drug prescribed. We performed a multivariate analysis and obtained the linear regression coefficients and their 95% confidence interval (CI). Results In a sample of 17177 pregnant women, 2.5% had a diagnosis of depression. The patients with depression had an average age of 32 years (SD 5.56) compared to the rest of the women who had an average age of 30 (SD 5.85) years of age. Obesity was present in 17.7% of patients with depression compared to 14.3% in the rest. A high percentage of women from Western Europe presented depression (2.9%); followed by women from Latin America (2.6%) and Eastern Europe (2.3%). The values for Africa, (0.8%) and Asia and the Middle East (0.5%) were significantly lower. We did not observe any relationship between depression and hypothyroidism, high blood pressure, and diabetes. Conclusions In our study, we found a prevalence of depression similar to the one found in other publications. As main risk factors, we identified age, weight, and geographical origin.

Identifying and managing the most critical side effects encourages patients to take medications regularly and adhere to the course of treatment. Therefore, priority should be given to the more important ones, among these side effects. However, the number of studies that make a priority examination is limited. There is a need for a new study that determines which of these effects are more priority to increase the quality of the treatment. Accordingly, this study aims to define the most important side effects of antidepressant drugs with a novel model. Quantum Spherical fuzzy M-SWARA technique is considered to compute the importance weights of the items. The main contribution of this study is that the most critical side effects can be understood for antidepressant drugs by establishing a novel decision-making model. The findings demonstrate that psychological side effects are defined as the most critical side effects of antidepressant drugs. Furthermore, physical side effects also play a key role in this condition. Side effects in antidepressant treatment have a great impact on the effectiveness of treatment and patient compliance. [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]

Simple Summary: Epigenetics plays a significant role in understanding depression, which is considered one of the most complex mental health disorders. Epigenetics includes all changes in gene expression that do not involve any modifications to DNA sequences. In depression, epigenetic changes may affect the activation or suppression of specific genes involved in mood regulation. Scientists have attempted to determine how specific environmental factors, such as stress or trauma, can trigger epigenetic changes that are closely linked to gene function. By studying these mechanisms, researchers have developed effective treatments and interventions for depression. This discovery not only provides a better understanding of the biological basis of depression, but also suggests new approaches for highly personalized treatments that may be available to individuals suffering from this widespread mental health disorder in the near future. Depression, a significant mental health disorder, is under intense research scrutiny to uncover its molecular foundations. Epigenetics, which focuses on controlling gene expression without altering DNA sequences, offers promising avenues for innovative treatment. This review explores the pivotal role of epigenetics in depression, emphasizing two key aspects: (I) identifying epigenetic targets for new antidepressants and (II) using personalized medicine based on distinct epigenetic profiles, highlighting potential epigenetic focal points such as DNA methylation, histone structure alterations, and non-coding RNA molecules such as miRNAs. Variations in DNA methylation in individuals with depression provide opportunities to target genes that are associated with neuroplasticity and synaptic activity. Aberrant histone acetylation may indicate that antidepressant strategies involve enzyme modifications. Modulating miRNA levels can reshape depression-linked gene expression. The second section discusses personalized medicine based on epigenetic profiles. Analyzing these patterns could identify biomarkers associated with treatment response and susceptibility to depression, facilitating tailored treatments and proactive mental health care. Addressing ethical concerns regarding epigenetic information, such as privacy and stigmatization, is crucial in understanding the biological basis of depression. Therefore, researchers must consider these issues when examining the role of epigenetics in mental health disorders. The importance of epigenetics in depression is a critical aspect of modern medical research. These findings hold great potential for novel antidepressant medications and personalized treatments, which would significantly improve patient outcomes, and transform psychiatry. As research progresses, it is expected to uncover more complex aspects of epigenetic processes associated with depression, enhance our comprehension, and increase the effectiveness of therapies. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) and its downstream tropomyosin receptor kinase B (TrkB) signaling pathway play pivotal roles in the resilience and action of antidepressant drugs, making them prominent targets in psychiatric research. Oxidative stress (OS) contributes to various neurological disorders, including neurodegenerative diseases, stroke, and mental illnesses, and exacerbates the aging process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) serves as the primary cellular defense mechanism against OS-induced brain damage. Thus, Nrf2 activation may confer endogenous neuroprotection against OS-related cellular damage; notably, the TrkB/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, stimulated by BDNF-dependent TrkB signaling, activates Nrf2 and promotes its nuclear translocation. However, insufficient neurotrophin support often leads to the downregulation of the TrkB signaling pathway in brain diseases. Thus, targeting TrkB activation and the Nrf2-ARE system is a promising therapeutic strategy for treating neurodegenerative diseases. Phytochemicals, including indole-3-carbinol (I3C) and its metabolite, diindolylmethane (DIM), exhibit neuroprotective effects through BDNF's mimetic activity; Akt phosphorylation is induced, and the antioxidant defense mechanism is activated by blocking the Nrf2-kelch-like ECH-associated protein 1 (Keap1) complex. This review emphasizes the therapeutic potential of I3C and its derivatives for concurrently activating neuronal defense mechanisms in the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

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

As major depressive disorder is becoming a more and more common issue in modern society, it is crucial to discover new possible grip points for its diagnosis and antidepressive therapy. One of them is endocannabinoid system, which has been proposed as a manager of emotional homeostasis, and thus, endocannabinoid alterations have been found in animals undergoing various preclinical models of depression procedures as well as in humans suffering from depressive-like disorders. In this review article, studies regarding those alterations have been summed up and analyzed. Another important issue raised by the researchers is the impact of currently used antidepressive drugs on endocannabinoid system so that it would be possible to predict reversibility of endocannabinoid alterations following stress exposure and, in the future, to be able to design individually personalized therapies. Preclinical studies investigating this topic have been analyzed and described in this article. Unfortunately, too few clinical studies in this field exist, what indicates an urgent need for collecting such data, so that it would be possible to compare them with preclinical outcomes and draw reliable conclusions. [ABSTRACT FROM AUTHOR]

A simple and sensitive indirect spectrophotometric method is developed for the assay of Adrenaline, Dopamine hydrochloride, and Methyldopa in their pure and pharmaceutical preparations. The method is based on the principle of oxidation of the above drugs with a known amount of the oxidizing agent, N-bromosuccinimide (NBS), in hydrochloric acid. The unreacted oxidant bleaches Ponceau 4R dye, then the absorbance of the remaining dye (∆A) is measured at 507 nm. The method obeyed Beer’s law within the concentration range of 3.5-10, 4-15, and 5-20 μg/mL, with molar absorptivity values of 8.01×104, 5.32×104, and 4.93×104 L. mol-1cm-1 for Adrenaline, Dopamine hydrochloride and Methyldopa, respectively. The recovery ranged between 99.15 to 100.61%, and the relative standard deviation (RSD) was less than 1.42 % for all drug compounds. The method was applied successfully to pharmaceutical preparations for the studied medicinal compounds from different origins, as its results were in good agreement with the original content of the drugs in their pharmaceutical formulations and with the standard addition procedure, which proved that there was no interference by the excipients.

N -acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in Major Depressive Disorder (MDD) pathophysiology. To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a pre-registered meta-analysis of Proton Magnetic Resonance Spectroscopy (1H-MRS) studies comparing NAA concentrations in chronic MDD (n = 1308) and first episode of depression (n = 242) patients to healthy controls (HC, n = 1242). Sixty-two studies were meta-analyzed using a random-effect model for each brain region. NAA concentrations were significantly reduced in chronic MDD compared to HC within the frontal lobe (Hedges' g = −0.330; p = 0.018), the occipital lobe (Hedges' g = −0.677; p = 0.007), thalamus (Hedges' g = −0.673; p = 0.016), and frontal (Hedges' g = −0.471; p = 0.034) and periventricular white matter (Hedges' g = −0.478; p = 0.047). We highlighted a gap of knowledge regarding NAA levels in first episode of depression patients. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. We highlighted field strength and correction for voxel grey matter as moderators of NAA levels detection. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression. • We compared 1H-MRS NAA levels between Major Depressive Disorder (MDD) and controls. • Only 8 studies reported NAA levels in first episode of depression. • Thalamic, frontal, occipital NAA was lower in chronic MDD compared to controls. • Antidepressants may reverse frontal NAA deficits, but further research is needed. • Field strength and correction for voxel grey matter fraction modify NAA detection. [ABSTRACT FROM AUTHOR]

The dimer of the neuronal receptor tyrosine kinase-2 (TrkB) transmembrane domains (TMDs) is a novel target for drug binding. Antidepressant drugs act as allosteric potentiators of brain-derived neurotrophic factor (BDNF) signaling through binding to TrkB. Cholesterol modulates the structure and function of TrkB. Agonist TrkB antibodies are being developed for neurodegenerative disorders. TrkB (neuronal receptor tyrosine kinase-2, NTRK2) is the receptor for brain-derived neurotrophic factor (BDNF) and is a critical regulator of activity-dependent neuronal plasticity. The past few years have witnessed an increasing understanding of the structure and function of TrkB, including its transmembrane domain (TMD). TrkB interacts with membrane cholesterol, which bidirectionally regulates TrkB signaling. Additionally, TrkB has recently been recognized as a binding target of antidepressant drugs. A variety of different antidepressants, including typical and rapid-acting antidepressants, as well as psychedelic compounds, act as allosteric potentiators of BDNF signaling through TrkB. This suggests that TrkB is the common target of different antidepressant compounds. Although more research is needed, current knowledge suggests that TrkB is a promising target for further drug development. [ABSTRACT FROM AUTHOR]

Antidepressant drugs play a crucial role in the treatment of mental health disorders, but their efficacy and safety can be compromised by drug degradation. Recent reports point to several drugs found in concentrations ranging from the limit of detection (LOD) to hundreds of ng/L in wastewater plants around the globe; hence, antidepressants can be considered emerging pollutants with potential consequences for human health and wellbeing. Understanding and implementing effective degradation strategies are essential not only to ensure the stability and potency of these medications but also for their safe disposal in line with current environment remediation goals. This review provides an overview of degradation pathways for amitriptyline, a typical tricyclic antidepressant drug, by exploring chemical routes such as oxidation, hydrolysis, and photodegradation. Connex issues such as stability-enhancing approaches through formulation and packaging considerations, regulatory guidelines, and quality control measures are also briefly noted. Specific case studies of amitriptyline degradation pathways forecast the future perspectives and challenges in this field, helping researchers and pharmaceutical manufacturers to provide guidelines for the most effective degradation pathways employed for minimal environmental impact. [ABSTRACT FROM AUTHOR]

Depression is detrimental to partnership stability. However, it remains unclear if and how the duration and timing of depression affect the risk of family dissolution. We conducted a Danish register-based cohort study of newly-formed cohabiting and married couples in 2008 and 2009, who were followed from the second year after family formation. Depressive episodes were defined by individual-level prescription patterns of antidepressant drugs (ATC codes N06A) in either partner. Family dissolution was characterized by the discontinuation of a shared residential address. Using Longitudinal Targeted Minimum Loss-based Estimation, we estimated the risk of family dissolution after 5 years of follow-up under various lengths and timings of depressive episodes. There were 102,335 families included. The covariate-adjusted risk of family dissolution in families without depressive episodes was 30.0 % (95 % CI 29.6–30.4 %) and 35.5 % (95 % CI 29.5–41.5 %) in families with at least one depressive episode during follow-up. The risk of family dissolution increased with the duration of depressive episodes to 42.2 % (95 % CI 40.8–43.6 %) for five coherent years of depression. Depression shortly after family formation carried higher risk of family dissolution; this risk was 42.3 % (95 % CI 38.4–46.3 %) for depression experienced in the first year of family formation versus 32.9 % (95 % CI 31.8–34.0 %) in the fifth year of family formation. Proxy measures of depression by antidepressant prescriptions fails to identify milder depression. Annual measures of family dissolution precluded more fine-grained analyses of time-intervals. Depression is disruptive to family stability, particularly with longer duration and early onset after family formation. • Depression substantially increased the risk of family dissolution. • Enduring depressive episodes was increasingly detrimental to relationship stability. • The dissolution-risk was higher in families where depression presented early after family formation. [ABSTRACT FROM AUTHOR]

Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on "prescription drug use-related software" illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug–device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer's disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx "active ingredients" also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug–device combination products are illustrated by Humira® (adalimumab) facing a "patent-cliff" competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies. [ABSTRACT FROM AUTHOR]

There is a growing concern that antidepressant drugs impair sexual function and adversely impact spermatogenesis and male fertility. Vitamin C is a natural antioxidant that plays a vital role in the male reproductive system. The present study investigated the ameliorating potential of vitamin C against citalopram (CTL)‐evoked testicular toxicity and spermatogenesis impairment in mice. Mice were randomly divided into six groups: control, CTL, vitamin C 100, vitamin C 200, CTL plus vitamin C 100, and CTL plus vitamin C 200. Adult male mice were intraperitoneally (ip) injected with 10 mg/kg of CTL for 35 days with or without vitamin C. At the end of the study, body and testes weight, sperm parameters, histopathology of testes, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (TUNEL assay) were evaluated. Our findings revealed that vitamin C restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and testes histopathology were significantly improved in the vitamin C‐administrated groups. Furthermore, vitamin C administration markedly alleviated CTL‐induced nitro‐oxidative damage, enhancing TAC levels, and reducing NO and MDA levels. Whilst CTL therapy induced a significant increase in the number of TUNEL‐positive cells compared to the control, the administration of vitamin C significantly prevented the apoptotic effects of CTL. Together, vitamin C therapy protects against CTL‐induced testicular damage via mitigating nitro‐oxidative stress and apoptosis, which provides evidence for vitamin C as a beneficial therapy against antidepressant drug‐associated reproductive toxicity and male sub/infertility. [ABSTRACT FROM AUTHOR]

Depression, a significant mental health disorder, is under intense research scrutiny to uncover its molecular foundations. Epigenetics, which focuses on controlling gene expression without altering DNA sequences, offers promising avenues for innovative treatment. This review explores the pivotal role of epigenetics in depression, emphasizing two key aspects: (I) identifying epigenetic targets for new antidepressants and (II) using personalized medicine based on distinct epigenetic profiles, highlighting potential epigenetic focal points such as DNA methylation, histone structure alterations, and non-coding RNA molecules such as miRNAs. Variations in DNA methylation in individuals with depression provide opportunities to target genes that are associated with neuroplasticity and synaptic activity. Aberrant histone acetylation may indicate that antidepressant strategies involve enzyme modifications. Modulating miRNA levels can reshape depression-linked gene expression. The second section discusses personalized medicine based on epigenetic profiles. Analyzing these patterns could identify biomarkers associated with treatment response and susceptibility to depression, facilitating tailored treatments and proactive mental health care. Addressing ethical concerns regarding epigenetic information, such as privacy and stigmatization, is crucial in understanding the biological basis of depression. Therefore, researchers must consider these issues when examining the role of epigenetics in mental health disorders. The importance of epigenetics in depression is a critical aspect of modern medical research. These findings hold great potential for novel antidepressant medications and personalized treatments, which would significantly improve patient outcomes, and transform psychiatry. As research progresses, it is expected to uncover more complex aspects of epigenetic processes associated with depression, enhance our comprehension, and increase the effectiveness of therapies.

Brain-derived neurotrophic factor (BDNF) and its downstream tropomyosin receptor kinase B (TrkB) signaling pathway play pivotal roles in the resilience and action of antidepressant drugs, making them prominent targets in psychiatric research. Oxidative stress (OS) contributes to various neurological disorders, including neurodegenerative diseases, stroke, and mental illnesses, and exacerbates the aging process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) serves as the primary cellular defense mechanism against OS-induced brain damage. Thus, Nrf2 activation may confer endogenous neuroprotection against OS-related cellular damage; notably, the TrkB/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, stimulated by BDNF-dependent TrkB signaling, activates Nrf2 and promotes its nuclear translocation. However, insufficient neurotrophin support often leads to the downregulation of the TrkB signaling pathway in brain diseases. Thus, targeting TrkB activation and the Nrf2-ARE system is a promising therapeutic strategy for treating neurodegenerative diseases. Phytochemicals, including indole-3-carbinol (I3C) and its metabolite, diindolylmethane (DIM), exhibit neuroprotective effects through BDNF’s mimetic activity; Akt phosphorylation is induced, and the antioxidant defense mechanism is activated by blocking the Nrf2-kelch-like ECH-associated protein 1 (Keap1) complex. This review emphasizes the therapeutic potential of I3C and its derivatives for concurrently activating neuronal defense mechanisms in the treatment of neurodegenerative diseases.

Objective: to explore the reciprocal relationship of depression and atrial fibrillation (AF). Methods: A literature search was conducted in Pub Med, Scopus, and Google Scholar using relevant terms for depression and AF and respective therapies. Results: There is evidence that depression is involved in the aetiology and prognosis of AF. AF, independently of its type, incurs a risk of depression in 20-40% of patients. Also, depression significantly increases cumulative incidence of AF (from 1.92% to 4.44% at 10 years); 25% increased risk of new-onset AF is reported in patients with depression, reaching 32% in recurrent depression. Hence, emphasis is put on the importance of assessing depression in the evaluation of AF and vice versa. Persistent vs paroxysmal AF patients may suffer from more severe depression. Furthermore, depression can impact the effectiveness of AF treatments, including pharmacotherapy, anticoagulation, cardioversion and catheter ablation. Conclusions: A reciprocal association of depression and AF, a neurocardiac link, has been suggested. Thus, strategies which can reduce depression may improve AF patients' course and treatment outcomes. Also, AF has a significant impact on risk of depression and quality of life. Hence, effective antiarrhythmic therapies may alleviate patients' depressive symptoms. [ABSTRACT FROM AUTHOR]

Depression is one of the greatest current mental disorders. Depressive disorder may affect everyone and it causes difficulties in social functioning and may lead to death via suicide. Depression is a serious problem because number of its cases is increasing, especially after pandemic of COVID-19. The oldest and the most approved theory which explains mechanism of depression’s development is a monoamine hypothesis. Effectiveness of most antidepressant drugs based on this theory. It assumes that the typical symptoms of depression are results of changed concentration of monoamines or incorrect monoaminergic transmission. The aim of this article is to present drugs which have influence on level of biogenic amines and are used in treatment of depressive disorders. Some of those drugs are the first choice in cure of this disease. In spite of adverse effects and often delayed onset of action of pharmacotherapy, it is still the first line in treatment of depression.

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Antidepressants are an important class of drugs to treat various types of depression. The determination of antidepressants is crucial in biological samples to control adverse effects in humans and study pharmacokinetics and bioavailability. Direct measurement of antidepressants in biological and water samples is a considerable challenge for analysts due to their low concentration, the high matrix effects of real samples, and the presence of metabolites of these drugs in biological samples. The challenge leads to using sample preparation processes as a critical step in determining antidepressants. Extraction and microextraction procedures have been widely utilized as sample preparation procedures for these drugs. The purposes of extraction or microextraction methods for antidepressant medications are to preconcentrate the analyte, reduce the matrix effects, increase the selectivity of the procedures, and convert the sample to a suitable format for introducing it into detection systems. In the review, the various extraction and microextraction methods of these drugs in biological, real water, and wastewater samples were investigated. The theory of each technique was briefly addressed to understand the features and factors affecting each method. The extraction and microextraction methods were classified based on their application for antidepressants, and the advantages and disadvantages of each technique were reviewed. The new developments to overcome the limitations of each procedure were discussed. The investigation indicated the number of applications of liquid-phase microextraction for extracting antidepressants has been almost equal to that of solid-phase microextraction. [ABSTRACT FROM AUTHOR]

Objectives: Administration of antidepressant drugs – principally selective serotonin reuptake inhibitors (SSRIs) – may induce clinically significant 'apathy' which can affect treatment outcomes adversely. We aimed to review all relevant previous reports. Methods: We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI). Results: According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants – usually SSRIs – can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate–modafinil–olanzapine combination. Conclusion: Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition. [ABSTRACT FROM AUTHOR]

Composite nanofibers, namely, polyvinyl alcohol (PVA), citric acid (CA), β-cyclodextrin (β–CD), and copper oxide nanoparticles (PVA/CA/β-cyclodextrin/CuO NPs), were developed as a novel, green, and efficient adsorbent in the pipette tip-micro-solid-phase extraction method (PT-µSPE), for the simultaneous extraction of three antidepressants drugs namely imipramine (IMP), citalopram (CIT), and clozapine (CLZ) in biological fluids before quantification by gas chromatography (GC-FID). Based on the obtained results from field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD), the successful synthesis of composite nanofibers was approved. Due to the presence of β-cyclodextrins and CuO NPs rich of functional groups on their surface, the nanofibers have high extraction efficiency. Under the optimal conditions, the linear range for imipramine, citalopram, and clozapine was 0.1 to 1000.0 ng mL−1 with a determination coefficient ≥ 0.99. The limits of detection (LODs) were in the range 0.03 to 0.15 ng mL−1. The relative standard deviation was 4.8 to 8.7% (within-day, n = 4) and 5.1 to 9.2% (between-day, n = 3) for 3 consecutive days. In addition, excellent clean-up was achieved which is a great advantage over other sample preparation methods. Finally, the ability of the developed method to extract the target analytes from the biological samples was evaluated. [ABSTRACT FROM AUTHOR]

Depressive symptoms are common among patients with glioblastoma, but patients are often not treated with antidepressants. There is only limited evidence on the association of antidepressant drug use with survival in glioblastoma. We performed a pooled analysis of patients treated within the CENTRIC, CORE, AVAglio and ACT‐IV trials to explore the relation of antidepressant drug use with progression‐free (PFS) and overall survival (OS) at baseline, at the start of maintenance therapy and at the start of maintenance cycle 4. We further assessed the association of antidepressant drugs with seizure, cognition, fatigue and a diagnosis of depression. Among more than 1700 patients, we found no significant association between the use of antidepressants at baseline or at the start of maintenance therapy and PFS or OS. However, we found OS, but not PFS, to be significantly worse in patients using antidepressants at the start of maintenance cycle 4. After adjustment for antiepileptic drug use and despite showing a trend for increased risk, seizures were not significantly associated with antidepressant drug use, nor was there a change in mini mental state examination (MMSE) scores or fatigue by antidepressant drug use at baseline. However, there was a significant positive association between antidepressant use at the start of maintenance treatment and fatigue during maintenance treatment. The association of antidepressant use at the start of maintenance cycle 4 with inferior OS of glioblastoma patients requires independent confirmation and further study. Further prospective trials should evaluate efficacy, side effects and associations with outcome of antidepressants in glioblastoma. [ABSTRACT FROM AUTHOR]

A considerable amount of literature has been published on antidepressants and cardiac ion channel dysfunction. The antidepressant paroxetine has been associated with Brugada syndrome and long QT syndrome, albeit on the basis of conflicting findings. The cardiac voltage-gated sodium channel (NaV1.5) is related to both of these syndromes, suggesting that paroxetine may have an effect on this channel. In the present study, we therefore carried out patch clamp experiments to examine the effect of paroxetine on human NaV1.5 channels stably expressed in human embryonic kidney 293 (HEK-293) cells as well as on action potentials of isolated rabbit left ventricular cardiomyocytes. Additionally, computer simulations were conducted to test the functional effects of the experimentally observed paroxetine-induced changes in the NaV1.5 current. We found that paroxetine led to a decrease in peak NaV1.5 current in a concentration-dependent manner with an IC50 of 6.8 ± 1.1 µM. In addition, paroxetine caused a significant hyperpolarizing shift in the steady-state inactivation of the NaV1.5 current as well as a significant increase in its rate of inactivation. Paroxetine (3 µM) affected the action potential of the left ventricular cardiomyocytes, significantly decreasing its maximum upstroke velocity and amplitude, both of which are mainly regulated by the NaV1.5 current. Our computer simulations demonstrated that paroxetine substantially reduces the fast sodium current of human left ventricular cardiomyocytes, thereby slowing conduction and reducing excitability in strands of cells, in particular if conduction and excitability are already inhibited by a loss-of-function mutation in the NaV1.5 encoding SCN5A gene. In conclusion, paroxetine acts as an inhibitor of NaV1.5 channels, which may enhance the effects of loss-of-function mutations in SCN5A. [ABSTRACT FROM AUTHOR]

These are the preliminary results of a 12-week non-randomized, open-label, non-inferiority study comparing the effectiveness of trazodone in an extended-release formulation (XR) versus SSRIs in the treatment of major depressive disorder (MDD). Participants (n = 76) were recruited, and 42 were assigned to the trazodone XR group and 34 to the SSRIs group. The choice of drug was based on clinical presentation and relied upon the attending physician. Assessments were made at five observation time points, at the following weeks: 0, and after 2, 4, 8, and 12 weeks. The evaluations included: symptoms of depression (MADRS, QIDS-clinician, and self-rated versions-primary study endpoints), anhedonia (SHAPS), anxiety (HAM-A), insomnia (AIS), psychosocial functioning (SDS), and therapeutic efficacy (CGI). At baseline, the trazodone group had significantly more severe depressive, anxiety, and insomnia symptoms and worse psychosocial functioning compared to the SSRIs group. After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of insomnia and depression. There were no differences between the groups in the frequencies of therapeutic response and remission, which indicated the non-inferiority of the trazodone XR treatment. In conclusion, our results showed that in a "real world" setting, trazodone XR is effective in the treatment of patients with MDD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is the leading cause of disability worldwide. Treatment with antidepressant drugs (ATD), which target monoamine neurotransmitters including serotonin (5HT), are only modestly effective. Monoamine oxidase (MAO) metabolizes 5HT to 5-hydroxy indoleacetic acid (5HIAA). Genetic variants in the X-chromosome-linked MAO-encoding genes, MAOA and MAOB, have been associated with clinical improvement following ATD treatment in depressed patients. Our aim was to analyze the association of MAOA and MAOB genetic variants with (1) clinical improvement and (2) the plasma 5HIAA/5HT ratio in 6-month ATD-treated depressed individuals. Clinical (n = 378) and metabolite (n = 148) data were obtained at baseline and up to 6 months after beginning ATD treatment (M6) in patients of METADAP. Mixed-effects models were used to assess the association of variants with the Hamilton Depression Rating Scale (HDRS) score, response and remission rates, and the plasma 5HIAA/5HT ratio. Variant × sex interactions and dominance terms were included to control for X-chromosome-linked factors. The MAOA rs979605 and MAOB rs1799836 polymorphisms were analyzed. The sex × rs979605 interaction was significantly associated with the HDRS score (p = 0.012). At M6, A allele-carrying males had a lower HDRS score (n = 24, 10.9 ± 1.61) compared to AA homozygous females (n = 14, 18.1 ± 1.87; p = 0.0067). The rs1799836 polymorphism was significantly associated with the plasma 5HIAA/5HT ratio (p = 0.018). Overall, CC/C females/males had a lower ratio (n = 44, 2.18 ± 0.28) compared to TT/T females/males (n = 60, 2.79 ± 0.27; p = 0.047). The MAOA rs979605 polymorphism, associated with the HDRS score in a sex-dependent manner, could be a useful biomarker for the response to ATD treatment. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder may be encountered in 17% of patients with epilepsy and in patients with drug-resistant epilepsy its prevalence may reach 30%. This indicates that patients with epilepsy may require antidepressant treatment. Purpose: Both pharmacodynamic and pharmacokinetic interactions between antiepileptic (antiseizure) and antidepressant drugs have been reviewed. Also, data on the adverse effects of co-administration of antiepileptic with antidepressant drugs have been added. This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology. Methods: The review of relevant literature was confined to English-language publications in PUBMED databases. Table data show effects of antidepressants on the seizure susceptibility in experimental animals, results of pharmacodynamic interactions between antiepileptic and antidepressant drugs mainly derived from electroconvulsions in mice, as well as results concerning pharmacokinetic interactions between these drugs in clinical conditions. Conclusion: Antidepressant drugs may exert differentiated effects upon the convulsive threshold which may differ in their acute and chronic administration. Animal data indicate that chronic administration of antidepressants could reduce (mianserin, trazodone) or potentiate the anticonvulsant activity of some antiepileptics (fluoxetine, reboxetine, venlafaxine). There are also examples of neutral interactions (milnacipran). [ABSTRACT FROM AUTHOR]

The use of FDA-approved drugs for new indications represents a faster and more economical way to find novel therapeutic agents for cancer therapy, compared to the development of new drugs. Repurposing drugs is advantageous in a pharmacological context since these drugs already have extensive data related to their pharmacokinetics, facilitating their approval process for different diseases. Several studies have reported the promising anticancer effects of sertraline, both alone and combined, in different types of cancer cell lines. Here, we performed a literature review on the anticancer potential of sertraline against different human cancer cells, more specifically in lung, colorectal, breast, hepatocellular, leukemia, brain, skin, oral, ovarian, and prostate cancer. Taken together, these findings suggest that sertraline decreases cell viability, proliferation, migration, and invasion, induces apoptosis, and causes cell cycle arrest in different types of cancer cells, besides being an established P-glycoprotein modulator. It was also found that this drug is able to modulate autophagy, cause DNA fragmentation, and induce radical oxygen species (ROS) formation. Moreover, it was found this drug targets important cellular pathways involved in tumorigeneses such as the TNF-MAP4K4-JNK pathway, the antiapoptotic pathway PI3K/Akt/mTOR, and the AMPK/mTOR axis. This drug also interferes with the TCTP/P53 feedback loop and with the cytosolic free Ca2+ levels. Together, these results suggest that sertraline may be a promising compound for further evaluation in novel cancer therapies. [ABSTRACT FROM AUTHOR]

The photochemical behavior of venlafaxine (VNX) in surface water was investigated using a hybrid theoretical-experimental-kinetic modeling approach. In addition to the direct photolysis quantum yield, the rate constants of the reactions between VNX and reactive photo-induced species (hydroxyl radicals, HO·; singlet oxygen, 1O 2 ; and triplet excited states of chromophoric dissolved organic matter, 3CDOM*) in sunlit water were measured under simulated solar radiation using competition kinetics. To elucidate possible degradation products, first-principles calculations were applied, followed by toxicity estimation by quantitative structure-activity relationship (QSAR) calculations. Furthermore, kinetic simulations of VNX persistence in an urban water reservoir of the São Paulo Metropolitan Region, Brazil, were performed. The results indicate low direct photolysis of VNX, with Φ VNX = (1.06 ± 0.18) × 10−2 mol Einstein−1. The measured values of the second-order reaction rate constants are k VNX, 3CDOM* = (3.98 ± 0.28) × 109 L mol−1 s−1 and k VNX,1O2 = (2.09 ± 0.17) × 107 L mol−1 s−1, which are lower than k VNX, HO· obs = (6.92 ± 0.37) × 109 L mol−1 s−1 and k VNX, HO· theo = 4.98 × 109 L mol−1 s−1. O-desmethylvenlafaxine, the most thermodynamically stable metabolite predicted by theoretical calculations, revealed potentially greater toxicity and, therefore, higher environmental risk to aquatic ecosystems. The estimated half-lives for VNX range from 9 to 62 days, depending on the season, local weather conditions and water quality parameters, the effects of which can be satisfactorily simulated with the aid of the modified photochemical fate model proposed in this work. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring for antidepressants (ADs) is vital due to the potentially serious consequences and disputes related to medical events. Therefore, we created a quick and convenient analysis way for separation and quantification of ADs., Methods: To ensure quantitative stability, we divided the 16 ADs or their metabolites into 4 pools (AD1-AD4), considering the hospital frequency that the clinician prescribed, the physicochemical properties of medicines, and the calibration range of selected ADs. After precipitation with methanol, the analytes were eluted for at least 3.5 min on a BEH C 18 analytical column by different gradient elution methods., Results: The LLOQ and LOD were 1.25-10 ng/mL and 0.42-5 ng/mL, respectively. High precision (<12 %) and accuracy (87.07-111.47 %) were demonstrated by quality control samples both within and between days. All the compounds were stable at room temperature and within -80 °C., Conclusion: The method is of wide clinical and laboratory interest due to simpler sample cleanup, shorter chromatographic run times, and wider calibration range compared to other methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Major depressive disorder may be encountered in 17% of patients with epilepsy and in patients with drug-resistant epilepsy its prevalence may reach 30%. This indicates that patients with epilepsy may require antidepressant treatment.Purpose: Both pharmacodynamic and pharmacokinetic interactions between antiepileptic (antiseizure) and antidepressant drugs have been reviewed. Also, data on the adverse effects of co-administration of antiepileptic with antidepressant drugs have been added. This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology.Methods: The review of relevant literature was confined to English-language publications in PUBMED databases. Table data show effects of antidepressants on the seizure susceptibility in experimental animals, results of pharmacodynamic interactions between antiepileptic and antidepressant drugs mainly derived from electroconvulsions in mice, as well as results concerning pharmacokinetic interactions between these drugs in clinical conditions.Conclusion: Antidepressant drugs may exert differentiated effects upon the convulsive threshold which may differ in their acute and chronic administration. Animal data indicate that chronic administration of antidepressants could reduce (mianserin, trazodone) or potentiate the anticonvulsant activity of some antiepileptics (fluoxetine, reboxetine, venlafaxine). There are also examples of neutral interactions (milnacipran).

For the first time, an acidic deep eutectic solvent (DES) comprised of malonic acid and ChCl was used to complete dissolution of Co‐Al, Ni‐Al, and Cu‐Al layered double hydroxides (LDHs) as sorbents in the vortex‐assisted in‐situ solid‐phase extraction of doxepin and amitriptyline followed by high‐performance liquid chromatography‐ultraviolet (HPLC‐UV). Moreover, the ability of urea:ChCl and ethylene glycol:ChCl was investigated to dissolve the LDH sorbents. The extraction conditions were optimized in terms of vortex time, molar ratio of Co2+:Al3+, NaOH concentration, and volume of DES based on the Box‐Behnen design. The linearity, limit of detection, and coefficient of determination R2 for both analytes were assessed as well. Recoveries of more than 93.1 % with relative standard deviations of less than 5.3 % were achieved for spiking urine and pharmaceutical formulation samples. [ABSTRACT FROM AUTHOR]

There has been growing recognition that major depressive disorder is a serious medical disorder that also affects children. This has been accompanied by an increased use of antidepressant drugs in adolescents; however, not all classes of antidepressants are effective in children and adolescents. There is an increasing need to understand the differences in antidepressant action in different developmental stages. There are some data indicating that the behavioral effect of chronic antidepressant treatment in adult rodents is dependent on hippocampal neurogenesis; however, it is not known which classes of antidepressant drugs induce hippocampal neurogenesis in adolescent rodents. Three classes of antidepressant drugs were tested in two age groups of Sprague Dawley rats, pre-adolescent (postnatal days 11–24) and adolescent (postnatal days 21–34): monoamine oxidase inhibitors (MAOIs); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); and tricyclic antidepressants (TCAs). To address which classes of antidepressant drugs might alter the rate of mitogenesis in neural progenitor cells in an adolescent rodent model, adolescent Sprague Dawley rats were treated with the thymidine analog 5-bromo-deoxy-2′-uridine (BrdU) on postnatal days 21 and 22 and antidepressant drugs or vehicle for 14 days (postnatal days 21–34). To address which classes of antidepressant drugs might alter the rate of neurogenesis, postnatal day-21 Sprague Dawley rats were treated with antidepressant drugs or vehicle for 14 days (postnatal days 21–34) and BrdU on postnatal days 33 and 34. In both experimental paradigms, BrdU-positive cells in the subgranular zone and the granule cell layer were counted. Newborn neurons were identified in the neurogenic paradigm by identifying cells expressing both the neuronal specific marker NeuN and BrdU using confocal microscopy. Only the SSRI fluoxetine significantly altered the basal mitogenic and neurogenic rates in adolescent rats. Treatment with the monoamine oxidase inhibitor (MAOI) tranylcypromine (TCP) and the TCA desipramine did not alter the rate of hippocampal neurogenesis in the adolescent rats. This is consistent with human clinical observations, where only SSRIs have efficacy for treatment of depression in patients under the age of 18. In pre-adolescent rats, postnatal days 11–24, none of the drugs tested significantly altered the basal mitogenic or neurogenic rates. All of the classes of antidepressant drugs are known to induce hippocampal neurogenesis in adult rats. The mechanisms of action underlying this developmental difference in antidepressant drug action between juveniles and adults are not known. [ABSTRACT FROM AUTHOR]

The International Classification of Diseases (10th Version) categorizes major depressive disorder (MDD) according to severity. Guidelines provide recommendations for the treatment of MDD according to severity. Aim of this study was to assess real-life utilization of psychotropic drugs based on severity of MDD in psychiatric inpatients. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) were analyzed according to the severity of MDD. From 2001 to 2017, 43,868 psychiatric inpatients with MDD were treated in participating hospitals. Most patients were treated with ≥ 1 antidepressant drug (ADD; 85.8% of patients with moderate MDD, 89.8% of patients with severe MDD, and 87.9% of patients with psychotic MDD). More severely depressed patients were more often treated with selective serotonin–norepinephrine reuptake inhibitors and mirtazapine and less often with selective serotonin reuptake inhibitors (p < 0.001 each). Use of antipsychotic drugs (APDs), especially second-generation APDs, increased significantly with severity (37.0%, 47.9%, 84.1%; p < 0.001 each). APD + ADD was the most used combination (32.8%, 43.6%, 74.4%), followed by two ADDs (26.3%, 29.3%, 24.9%). Use of lithium was minimal (3.3%, 6.1% ,7.1%). The number of psychotropic drugs increased with severity of MDD—patients with psychotic MDD had the highest utilization of psychotropic drugs (93.4%, 96.5%, 98.7%; p < 0.001). ADD monotherapy was observed to a lesser extent, even in patients with non-severe MDD (23.2%, 17.1%, 4.4%). Findings reveal substantial discrepancies between guideline recommendations and real-life drug utilization, indicating that guidelines may insufficiently consider clinical needs within the psychiatric inpatient setting. [ABSTRACT FROM AUTHOR]

In this study, hydrogen production was analyzed along with methane and carbon dioxide generation using paroxetine, venlafaxine, and o-desmethylvenlafaxine (ODV) as substrates in single-chamber microbial electrolysis cells (MECs). Combinations of all three drugs were examined at concentrations of 750 ng/mL and 170 ng/mL. At the beginning of MEC operations using a 750 ng/mL mixture of drugs, there was no hydrogen or methane, but carbon dioxide was detected. When the concentration of the drug mixture was reduced to 170 ng/mL, MECs produced hydrogen and methane gas. Removal of the drugs during MEC operations was also analyzed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Paroxetine, venlafaxine and ODV drugs were removed up to 99% by MECs. In conclusion, MECs could offer an alternative treatment method for wastewaters containing psychoactive pharmaceuticals with the added benefit of fuel hydrogen generation. HIGHLIGHTS Psychoactive pharmaceuticals generated hydrogen in microbial electrolysis cells.; 99% of paroxetine, venlafaxine and ODV drugs were removed with MECs.; Cytotoxic analysis was performed on the ECV-304 cell line using the MTT assay.; MECs could be used for wastewater contaminated with psychoactive drugs.; Additionally, simultaneous hydrogen generation could be achieved.;

Background:Patients on antidepressant therapy have no contact with their physicians until their next appointment, which in most cases could be more than two weeks apart. This crucial time is of utmost importance as this could assess the patient's will to follow the prescribed therapy and the general belief about the benefits of using antidepressant treatment. Thus medication adherence is necessary to reduce the risk of suicidal tendencies and mortality in these patients. The study aimed to evaluate medication adherence and adherence to antidepressant therapy in patients with major depressive disorder.Methodology:in this cross-sectional study, a total of 101clinically diagnosed patients with Major Depressive Disorder (MDD) were included in the study from psychiatric and medical OPD from June 2018 to June 2019, from Jinnah Medical College Hospital (JMCH). Belief about medicines questionnaire (BMQ specific and BMQ general), regarding their views about the prescribed medication and the modified questionnaire of the medication adherence scale used, scores were calculated to give a numerical value to measure the adherence to antidepressant medication.Results:According to the study, 101 patients with major depressive disorder had an overall good belief about medication but have low adherence. Belief about medicines questionnaire (based on BMQ) BMQ-the specific q1-10 score was 36.54 (necessity, concern), BMQ-general 27.98 score, q11-18 (overuse and harm). Regarding their views about the prescribed medication. 86% of participants with the major depressive disorder had low adherence (scores 0-5), and those with high adherence were only 14% (scores 6-8). The patients diagnosed with the major depressive disorder who had co-morbid (diabetes, hypertension, hypothyroidism, etc.) had better adherence for their prescribed treatment as compared to those without co-morbid.Conclusion:This study indicates that although patients with major depressive disorder from tertiary care hospitals in Karachi had a positive belief about medication but have low adherence to antidepressant therapy.

[Display omitted] GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily of the GPCR superfamily, which is the largest family of membrane protein receptors in the human genome. Studies in recent years have demonstrated that GPR56 is integral to the normal development of the brain and functions as an important player in cortical development, suggesting that GPR56 is involved in many physiological processes. Indeed, aberrant expression of GPR56 has been implicated in multiple neurological and psychiatric disorders, including bilateral frontoparietal polymicrogyria (BFPP), depression and epilepsy. In a recent study, it was found that upregulated expression of GPR56 reduced depressive-like behaviours in an animal model of depression, indicating that GPR56 plays an important role in the antidepressant response. Given the link of GPR56 with the antidepressant response, the function of GPR56 has become a focus of research. Although GPR56 may be a potential target for the development of antidepressants, the underlying molecular mechanisms remain largely unknown. Therefore, in this review, we will summarize the latest findings of GPR56 function in neurological and psychiatric disorders (depression, epilepsy, autism, and BFPP) and emphasize the mechanisms of GPR56 in activation and signalling in those conditions. After reviewing several studies, attributing to its significant biological functions and exceptionally long extracellular N-terminus that interacts with multiple ligands, we draw a conclusion that GPR56 may serve as an important drug target for neuropsychological diseases. [ABSTRACT FROM AUTHOR]

Aim. The efficacy of vortioxetine in major depressive disorder has been evaluated in many studies. However, there is a lack of studies assessing vortioxetine in bipolar depression. Material and method. In 60 patients with bipolar depression, vortioxetine 10-20 mg daily was added to current mood stabilizing medication during 24-week, naturalistic, openlabel study. The most frequent mood stabilizers were lamotrigine, quetiapine, olanzapine, and valproates. The therapeutic efficacy was evaluated by the Clinical Global Impression - Improvement (CGI-I) and Clinical Global Impression - Severity (CGI-S) scales. Patients were classified as responding to vortioxetine when they achieved 1 or 2 points on the CGI-I scale at any stage of observation. The criterion of remission was defined as score 1 at the CGI-S. Results. 73% of all patients (44/60) responded to vortioxetine and 52% (31/60) achieved clinical remission of depressive symptoms (in mean 8.97 ± 4.05 weeks). There were no significant associations between vortioxetine response/remission rates and: (1) the dose, (2) BD type, (3) clinical stage, (4) presence of rapid cycling, (5) history of psychotic symptoms, analyzed depressive symptoms, and (6) concomitantly used mood stabilizer. 4 patients (6.7%) stopped treatment due to adverse effects (nausea), and 7 patients (11.7%) discontinued treatment due to the phase switch. 14 patients (23%) experienced a loss of vortioxetine effectiveness after the initial response or remission. Conclusions. The results indicate relatively high rates of response and remission during 24-week treatment in depressed bipolar patients receiving vortioxetine concomitantly with a mood stabilizer. This may indicate that vortioxetine added to a mood stabilizer may constitute an efficient and well tolerated therapeutic option in bipolar depression. [ABSTRACT FROM AUTHOR]

In recent years, analytical chemistry has been facing new challenges, particularly in developing low-cost, green, and easy-to-reproduce methods. In this work, a simple, reproducible, and low-cost electrochemical (voltammetric) molecularly imprinted polymer (MIP) sensor was designed specifically for the detection of trazodone (TZD). Trazodone (TZD) is an antidepressant drug consumed worldwide since the 1970s. By combining electropolymerization (surface imprinting) with screen-printed electrodes (SPCEs), the sensor is easy to prepare, is environmentally friendly (uses small amounts of reagents), and can be used for in situ analysis through integration with small, portable devices. The MIP was obtained using cyclic voltammetry (CV), using 4-aminobenzoic acid (4-ABA) as the functional monomer in the presence of TZF molecules in 0.1 M HCl. Non-imprinted control was also constructed in the absence of TZD. Both polymers were characterized using CV, and TZD detection was performed with DPV using the oxidation of TZD. The polymerization conditions were studied and optimized. Comparing the TZD signal for MIP/SPCE and NIP/SPCE, an imprinting factor of 71 was estimated, indicating successful imprinting of the TZD molecules within the polymeric matrix. The analytical response was linear in the range of 5–80 µM, and an LOD of 1.6 µM was estimated. Selectivity was evaluated by testing the sensor for molecules with a similar structure to TZD, and the ability of MIP/SPCE to selectively bind to TZD was proven. The sensor was applied to spiked tap water samples and human serum with good recoveries and allowed for a fast analysis (around 30 min). [ABSTRACT FROM AUTHOR]

Many central nervous system (CNS) diseases, including major depressive disorder (MDD), are underpinned by the unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress. New, more efficient, therapeutic options for MDD are needed to avoid adverse effects and drug resistance. Therefore, the aim of the work was to determine whether UPR signalling pathway activation in astrocytes may serve as a novel target for antidepressant drugs. Among the tested antidepressants (escitalopram, amitriptyline, S-ketamine and R-ketamine), only S-ketamine, and to a lesser extent R-ketamine, induced the expression of most ER stress-responsive genes in astrocytes. Furthermore, cell viability and apoptosis measuring assays showed that (R-)S-ketamine did not affect cell survival under ER stress. Under normal conditions, S-ketamine played the key role in increasing the release of brain-derived neurotrophic factor (BDNF), indicating that the drug has a complex mechanism of action in astrocytes, which may contribute to its therapeutic effects. Our findings are the first to shed light on the relationship between old astrocyte specifically induced substance (OASIS) stabilized by ER stress and (R-)S-ketamine; however, the possible involvement of OASIS in the mechanism of therapeutic ketamine action requires further study. [ABSTRACT FROM AUTHOR]