Opioid use and abuse in adolescents and young adults; dealing with science, laws and ethics: Charming the COBRAS

Disease-a-Month, Год журнала: 2025, Номер unknown, С. 101853 - 101853

Опубликована: Янв. 1, 2025

Язык: Английский

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Trends in research on novel antidepressant treatments

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 27, 2025

Mood disorders, such as major depressive disorder and bipolar disorder, are among the most common mental illnesses a leading cause of disability worldwide. Key symptoms these conditions include depressed mood or anhedonia, sleep psychomotor disturbances, changes in appetite weight, fatigue loss energy. Prolonged cognitive disturbances further impair ability to think concentrate often accompanied by persistent feelings worthlessness excessive guilt. Collectively, underscore depression serious, long-term global health issue. In addition, clinical studies indicate growing number patients experiencing difficulties responding treatment, even long term. This phenomenon poses significant challenges for healthcare professionals, families, alike. As result, there is an urgent need therapies that both rapid-acting safe. review aims summarize prevailing trends research on novel antidepressants, emphasizing their diversity multi-directional mechanisms action. The development drugs increasingly focused achieving high efficacy, particularly treatment-resistant depression. Such advances offer potential rapid therapeutic effects without prolonged tedious administration older generation antidepressants. Findings from using animal models continue play crucial role predicting designing new strategies. These remain indispensable understanding physiological newly developed compounds, thereby guiding creation innovative treatments.

Язык: Английский

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Current Trends in Clinical Trials of Prodrugs

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 210 - 210

Опубликована: Фев. 4, 2025

The development of new drugs is a lengthy and complex process regarding its conception ideation, passing through in silico studies, synthesis, vivo clinical trials, approval, commercialization, with an exceptionally low success rate. lack efficacy, safety, suboptimal pharmacokinetic parameters are commonly identified as significant challenges the discovery drugs. To help address these challenges, various approaches have been explored medicinal chemistry, including use prodrug strategies. As well-established approach, design remains best option for improving physicochemical properties, reducing toxicity, increasing selectivity, all while minimizing costs saving on biological studies. This review article aims to analyze current advances using approach that has allowed advance drug candidates trials last 10 years. presented here aim inspire further molecular optimization processes highlight potential this strategy facilitate advancement compounds study phases.

Язык: Английский

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The Assessment of the Safety Profile of Selective Serotonin Reuptake Inhibitors Versus Other Antidepressants: Drug–Drug Interaction Insights from EudraVigilance

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(4), С. 1208 - 1208

Опубликована: Фев. 12, 2025

Depression persists as one of the illnesses described relentlessly through centuries because it affects a large group people. Background/Objectives: The treatment depression consists various therapeutic agents, among which selective serotonin reuptake inhibitors (SSRIs) are elective. As polypharmacy tends to become norm in modern days, study real-life occurrence drug-drug interactions is imperative. aim this was evaluation (DDIs) between antidepressant medicines, namely SSRIs (each representative) versus eleven representatives from other classes. Methods: Based on spontaneous safety reports (ICSRs) uploaded EudraVigilance until end July 2024, descriptive and disproportionality analyses were performed, results interpreted context pharmacologic variability. Results: focus 137,369 ICSRs while for antidepressants, amitriptyline, clomipramine, duloxetine, venlafaxine, mirtazapine, bupropion, trazodone, tianeptine, agomelatine, brexpiprazole, esketamine, total 155,458 registered. most notable differences appeared psychiatric adverse drug reactions. Except fluvoxamine (n = 463), remaining had higher number DDIs reported 1049 escitalopram n 1549 sertraline) compared antidepressants. However, similar numbers duloxetine 1252) venlafaxine 1513). Sertraline unspecified with probability all drugs (e.g., esketamine ROR: 9.37, 95% CI: 5.17-16.96, tianeptine 4.08, 2.49-6.69, etc.). Conclusions: SSRIs, although known influence cytochrome P450 isoenzymes, have not shown inhibitory any selected reference. appears more concerning than Still, further real world studies related needed complete relevant knowledge level.

Язык: Английский

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Disruptions in serotonin- and kynurenine pathway metabolism in post-COVID: biomarkers and treatment

Frontiers in Neurology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

This opinion article attempts to connect knowledge about post-Covid syndrome (PCS) gained in neuropsychiatry and immunology. It discusses some misunderstandings PCS light of the interplay between serotonergic system kynurenine pathway (KP). From a new perspective, potential biomarkers for further research therapeutic targets are identified.Due severity extent PCS, researchers urgently searching its causes treatments. For neurocognitive autonomic nervous problems such as present it is common encounter dysregulated neurotransmitter systems. Among neurotransmitters, serotonin plays special role immune regulating inflammatory responses by central peripheral mechanisms (1)(2)(3)(4)(5). Serotonin -also known 5-hydroxytryptamine (5-HT) -is with stimulating effect that influences memory, mood, selfconfidence, sleep, emotion, orgasm eating (6)(7)(8)(9).Serotonin not only binds receptors on neurons, but also cells (3,5,10,11). Many studies have indicate receptors, especially 5-HT3 (one receptors), involved pathogenesis chronic conditions (5,10,11). Therapeutic applications receptor antagonists instance been reported rheumatoid arthritis (5,11,12). An essential amino acid KP tryptophan, precursor both (see figure1), we get through food part regular diet (13). The creating an important energy factor modulated infection stress (1,5)and subsets T helper 17 (Th17 cells) produce cytokines signaling function (14).Strong alterations intestinal gene expression upregulate genes viral recognition inflammation pathways downregulate nutrient metabolism, like tryptophan (15). downregulation result serum reduction Various suspect this might be cause complaints (15)(16)(17)(18)(19).In I address question whether disruptions serotonin-and metabolism lead treatment PCS.In study 'Serotonin post-acute sequelae infection' Wong et al. (15) they investigated four human cohorts, animal models organoid cultures. First, conducted among 1540 patients who presented center severe complaints. They identified eight clusters based clinical symptoms, varying from mainly physical problems, loss strength muscles, memory disorders. performed targeted plasma metabolomics 58 representative 3-22 months after found compared 30 healthy controls.For finding three causes: a) diminished absorption tryptophan. Because angiotensin converting enzyme (ACE2) these strongly decreased. Furthermore, COVID-19 virus spike proteins attaches (20,21). As consequence, during infection, has compete over reduced number ACE2 receptors; b) micro-clots thrombocytes. Thrombocytes contain serotonin. reduce thrombocytes thus availability serotonin; c) enhanced monoamine oxidase (MAO) promotes breakdown serotonin.In Sadlier (17), cohort 20 hospitalized were controls, 4-6 6-9 infection. Levels multiple metabolites immunomodulatory properties elevated quinolinate, toxic metabolite. There levels other things glutamate (a neurotransmitter) level was increased.Su (18) longitudinal multi-omic analysis (n=209). followed immediately Covid-19 had less symptoms. measured autoantibodies, specific RNAemia, metabolic profiles, global proteomic blood mononuclear (PBMCs) draws. no 457 controls. What striking stands out reporting neurological symptoms exhibited associated negative regulation circadian sleep/wake cycle. hormone melatonin responsible produced brain (in pineal gland) serotonin.Wong conclude serious greater chance permanently retaining than mild checked Peluso (22) did indeed negatively correlate complaints.However, retrospective Mathé (19) using Liquid Chromatography -Mass Spectrometry (lc-ms/ms) technology 34 at least 6 complaints, which 14 controls.Although colleagues much more extensive most comprehensive all interesting results, agree conclusion reliable biomarker should used routine diagnostic assessment, two arguments.The first reason cannot cross blood-brain barrier appears reaches via cranial nerve, vagus nerve normally uses Acetylcholine (Ach) (9). So, directly related brain. Based models, assume PCS. In vivo, however, technically very difficult measure With possible techniques (microdialysis, functional magnetic resonance imaging (fMRI), fast-scan cyclic voltammetry (FSCV), genetically encoded indicators (GESIs) positron emission tomography (PET) either spatiotemporal resolution too poor or technique invasive or/and expensive .However, vivo you (23). authorsWong can move up hippocampus, control causing disorders our describe into 95 selective reuptake inhibitors (SSRIs) 'Treatment SSRIs' ( 16), give however another explanation. We hypothesize occurs brainstem After all, pons origin serotoninergic there, axons sent throughout (CNS) (6,7). afferent arises (6,7) full attach (20). Hypometabolic areas (24,25).Further corroboration argument rRecent Besteher (26) confirms argument. fMRI scans suffering neuropsychiatric (n = 30) significantly larger gray matter volumes (GMV) controls 20). Such example prefrontal cortex (PFC) -which range higher order cognitive functions limbic (27). predominates (27,28). authors state enlargement GMV could sign recovery neurogenesis compensation (26). However, Another explanation cerebral swelling caused reactions.Using PET -for transmission systems -researchers see exactly what happening enlarged Given persist, seems likely pathology. Moreover, provides plausible positive SSRIs when there something wrong balance those regions (16).Furthermore, Su melatonin, serotonin, reduced. additional support-contrary -that may reduced.The second reject biomarker, variability degree variable cohorts different (15,(17)(18)(19). probably many variables studies. as: time passed measurement: ranging 0 22 months, their exact quantification (especially subjective complaints) subgroups belonged cohort. believe methodology therefore results vary research.Unlike (9,13) better option (14,16). expected if instead levels, case comparative above preferably comparable.Beside given colleagues, fourth cause: KP, create nicotinamide adenine dinucleotide (NAD+), interacts extensively system, activated (14,(29)(30)(31). formation process demands lot 14) figure1) because deficiency (9).In study, decline lasted longer. Therefore, major reduction. Guo (30) show persistently INDO-2, stimulates production (figure 1). Cron (14) (such quinoline), while depleted. Additionally, Cysique significant relationship impairment (29). These overactivity KP. active left Figure 1 2.4. overactive deficiencies hormones neurotransmitters illustrates too. regulates cycle (17,32). sleep (16,33).Too due runaway feedback loop blocks tetrahydrobiopterin (BH4), coenzyme dopamine, turn ensures (nor)epinephrine Norepinephrine sympathetic increases frequency force muscle contractions (34)why symptom SNRI (selective norepinephrine inhibitor) SSRI (16).If look metabolites, quinolinic glutaminergic antagonists. accumulation (35) leads various concentration palpitations (35), often suffer (16,33). That why recommend (16) Nacetylcysteine drug restore (35). (36). stimulatesexcept besides pathological propose would preferable choose 5-hydroxytryptophan (5-HTP, confused 5-HT)5hydroxytryptophan) 5-HTP direct does feed barrier. 2.5.2. reduces -to lesser -norepinephrine presynaptic neuron allows synapse transmit signal postsynaptic longer period Normally usually described depression anxiety (37).Wong mice treated fluoxetine (an SSRI) improved Previously, several took SSRIs, lower developing (38)(39)(40)(41)(42)(43).In exploratory thirds PCS-patients showed considerable even strong being (16). confirmed hypothesis regarding importance formulated seven action one hypothetical mechanism. short: , short. instance, a. influence hypothalamic -pituitary -adrenalaxis (HPA-axis, system) (44-51), b. circulatory (52,53), c. . Bby prolonging clotting theoretically help dissolve microclots (54), d. oxidative e. tThe fluvoxamine shown extra anti-inflammatory effects inhibiting sphingomyelinase (ASM) (55), f. pro-inflammatory interleukin 2 (IL 2) IL CNS (56) -in achieve effects, must then sigma1 agonist receptor) (56),. g. stimulate hippocampus (9,57). Finally, slow down (9).Disruptions -and provide clear direction advancing line inquiry. literature noticed While evident scientists explore focus route (14,(29)(30)(31) (15,(17)(18)(19)36), typically overlook possibility routes related, regard pathology overlooked.Additionally, sSerotonin assessment turned (15,(17)(18)(19)22). Tryptophan option. comparable.Toxic good well, (29).Wong advised do examine (15)(16)(17)36). A randomized controlled trial (RCT) follow under strict conditions, testing pharmacogenetic profile advance, since absorb break quickly slowly lack desired side effects. excluded RCT outside context RCT. sensitive stop increasing dosage threatens tip without affecting requirements RCT.Furthermore recommended Therefore option.This review call collaboration immunologists, neurologists psychiatrists field neuroimmunology. already examples psychiatric diseases immunologically, schizophrenia (58)(59)(60)(61)(62), childhood (61,63,64) still unravel neuroimmunology immunological psychotropic drugs considered. (KP) same building block system. From: Treatment

Язык: Английский

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BDNF and proBDNF serum levels during antidepressant treatment in adolescent girls with a first-lifetime episode of depression: A prospective case-controlled study

Journal of Affective Disorders, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Linking Electronic Health Record Prescribing Data and Pharmacy Dispensing Records to Identify Patient-Level Factors Associated With Psychotropic Medication Receipt: Retrospective Study

JMIR Medical Informatics, Год журнала: 2025, Номер 13, С. e63740 - e63740

Опубликована: Март 4, 2025

Abstract Background Pharmacoepidemiology studies using electronic health record (EHR) data typically rely on medication prescriptions to determine which patients have received a medication. However, such do not affirmatively indicate whether these been filled. External dispensing databases can bridge this information gap; however, few established methods exist for linking EHR and pharmacy records. Objective We described process prescribing with records from Surescripts. As use case, we considered the resulting fills psychotropic medications among pediatric patients. evaluated how affects identifying receiving prescribed assessing association between filling subsequent behaviors. Methods This retrospective study identified all new younger than 18 years of age at Duke University Health System in 2021. linked proximate dates matching codes RxNorm concept unique identifiers National Drug Codes. demographic, clinical, service characteristics assess differences who did versus fill prescriptions. fit least absolute shrinkage selection operator (LASSO) regression model evaluate predictability fill. then time-to-event models patient filled prescription future provider visit. Results 1254 prescription. In total, 976 (77.8%) their within 30 days encounters. Thus, set as cut point defining valid Patients differed those several key factors. Those had slightly higher BMIs, lived more disadvantaged neighborhoods, were likely public insurance or self-pay, included proportion male prior well-child visits primary care providers Additionally, anxiety diagnoses selective serotonin reuptake inhibitors The LASSO achieved an area under receiver characteristic curve 0.816. time follow-up visit same was censored 90 after initial encounter. showed levels visits. marginal hazard ratio 1.673 (95% CI 1.463‐1.913) Using propensity-based weight, calculated weighted 1.447 1.257‐1.665). Conclusions Systematic existed Incorporating external into EHR-based informs receipt associated outcomes.

Язык: Английский

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Serotonergic Antidepressants Are Associated with Increased Acute Bleeding Events Following Femur Fracture Fixation: A Nationwide Matched Cohort Analysis of 5,477 Patients

Injury, Год журнала: 2025, Номер 56(4), С. 112236 - 112236

Опубликована: Март 8, 2025

Язык: Английский

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Exosomes and their roles in major depressive disorder: an overview of the research progress and perspectives

Deleted Journal, Год журнала: 2025, Номер unknown, С. 100035 - 100035

Опубликована: Март 1, 2025

Язык: Английский

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The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats

Pharmacology Research & Perspectives, Год журнала: 2025, Номер 13(2)

Опубликована: Апрель 1, 2025

ABSTRACT Anxiety disorder is a persistent, widespread, and intractable mood disorder, the available pharmacotherapies have limited efficacy with significant side effects. Trace amine‐associated receptor 1 (TAAR1) an emerging drug target for neuropsychiatric disorders. This study examined effects underlying mechanisms of novel TAAR1 agonist, PCC0105004, in rat model CUMS‐induced anxiety‐like behavior. The elevated zero maze open field tests test were employed to evaluate anti–anxiety‐like activity PCC0105004. PCC0105004 dose‐dependently attenuated behaviors rats without affecting spontaneous activity. Morphologically, PCC0104005 decreased density dendritic spines amygdala. For mechanistic studies, whole‐genome transcriptomic analysis revealed differences patterns amygdala gene expression anxiety model. These data further confirmed by using RT‐qPCR western blotting, revealing alterations associated genes ( Col1a1, DCN, Ewsr1 ) known regulate synaptic plasticity, was able reverse these changes. results suggest that promising anxiolytic candidate pharmacotherapy warrants examination development.

Язык: Английский

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