Search Results (210)

Background/Objectives: Adults with intellectual disability (ID) experience high rates of psychiatric comorbidity but often face diagnostic challenges and treatment barriers, leading to inappropriate psychotropic medication use. This study examined the extent to which specialized psychiatric assessment and improved diagnostic accuracy had an impact on medication management and clinical outcomes in adults with ID and co-occurring psychiatric disorders. Methods: This observational retrospective study analyzed medical records from 25 adults with ID who underwent specialized psychiatric assessment at a community-based service in Italy between January 2023 and January 2024. Psychopathological diagnoses were established according to Diagnostic Manual—Intellectual Disability, Second Edition (DM-ID2) criteria, based on clinical observation and a comprehensive assessment using validated instruments. Clinical outcomes were assessed using a psychometric tool encompassing multiple psychopathological and behavioral dimensions. Data on psychotropic prescriptions and side effects were also collected. Non-parametric analyses were performed, with significance set at α = 0.05. Results: The proportion of patients with a psychiatric diagnosis increased from 32% to 96% after specialized assessment (p < 0.001), with notable rises in depressive (0% to 32%), bipolar (8% to 36%), anxiety (4% to 24%), and impulse control (0% to 16%) disorders. First-generation antipsychotic prescriptions decreased (from 36% to 8%, p = 0.023), while antidepressant use increased (from 12% to 52%, p = 0.004). The mean number of side effects per patient declined from 1.6 to 0.5 (p < 0.001), particularly the elevated prolactin level and psychomotor retardation. Significant improvements were observed in symptom intensity and frequency across multiple domains, including aggression, mood disturbances, and compulsions (p < 0.001). Conclusions: In this single-center retrospective study, specialized psychiatric assessment was associated with improved diagnostic accuracy, medication management, and clinical outcomes in adults with ID. The increase in psychiatric diagnoses likely reflects improved identification, addressing key challenges in precision diagnosis for people with neurodevelopmental disorders. Although the overall number of prescribed medications remained stable, optimization of treatment regimens reduced first-generation antipsychotic use and related adverse effects. These findings indicates that access to specialized assessment and precision diagnosis could improve psychopharmacological interventions and outcomes for this vulnerable population, but larger, multi-center and longer-term studies are needed to confirm these results. Full article

Agomelatine (AG) is a novel antidepressant characterized by distinct mechanism of action and minimal side effects. However, extensive first-pass hepatic metabolism limits its clinical efficacy after oral administration, leading to low bioavailability (<5%). To get around these restrictions, the current study set out to create and assess a rectal thermosensitive in situ gel using biosynthesized AG-silver nanoparticles (AG-AgNPs). AG-AgNPs were successfully synthesized with gum acacia as a stabilizing agent, using silver nitrate as a precursor, and ascorbic acid as a reducing agent. The in situ gel formulation was optimized using a 3² factorial design, and then physicochemical, in vitro, and in vivo assessments were conducted. Nanoparticle formation was also evidenced by the appearance of a visible color change, UV-VIS, TEM, and XRD analysis techniques, which depicted spherical-shaped nanoparticles and a crystalline nature. The formulated optimized thermosensitive in situ gel showed good properties, which included drug content of 91.64%, gelation temperature of 26.63 °C, pH of 7.2, gel strength of 36.98 s, and sustained drug release of 80.24% in 6 h. The relative bioavailability in animal studies showed a remarkable increase in systemic availability with 277.5% relative bioavailability in comparison to an oral tablet formulation. In summary, results show that the AG-AgNP-loaded thermosensitive in situ gel could have potential use as a rectal delivery drug for bypassing first-pass effects and improving bioavailability for the drug Agomelatine. Full article

Since the introduction of the NMDA receptor antagonist (S)-ketamine for depression therapy, it has become evident that the glutamatergic hypothesis of depression, proposed over 20 years ago, was justified and based on solid foundations. A significant breakthrough with this drug is its ability to produce a rapid and relatively long-lasting antidepressant effect in patients who are resistant to traditional depression treatments, both pharmacological and non-pharmacological. However, alongside its beneficial effects, (S)-ketamine can cause several side effects that make it a less safe option. As a result, strategies are being explored to mitigate the risks associated with its use. These strategies include leveraging the shared mechanism of action between ketamine and various modulators of the glutamatergic system. Preclinical studies have shown that low doses of mGlu₂ and mGlu₅ receptor antagonists can enhance the therapeutic effects of ketamine or its enantiomers without producing the typical side effects associated with ketamine. This review discusses the research on this synergistic effect, the underlying mechanisms, and the role of mGlu₂ and mGlu₅ receptors in the antidepressant action of ketamine. Full article

Background and Objectives: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficits, restricted interests, and repetitive behaviors. At present, there is no pharmacological intervention that reliably targets the core symptoms of ASD; instead, medications are primarily used to manage associated or concurrent symptoms such as irritability, aggression, anxiety, attention difficulties, and sleep disturbances. This review summarizes the current evidence for pharmacological treatments in ASD, emphasizing how these interventions are used in a symptom-focused, adjunctive manner, and highlighting efficacy, mechanisms, limitations, and emerging therapeutic targets. Methods: A comprehensive literature review was conducted across PubMed, Cochrane Library, and Embase to identify clinical trials, systematic reviews, meta-analyses, and preclinical studies on pharmacological interventions for ASD. Seventy-seven references were integrated to reflect the current state of evidence. Results: Established pharmacological strategies include atypical antipsychotics for severe irritability and aggression, as well as antidepressants, stimulants and non-stimulant agents, mood stabilizers, and anxiolytics for selected comorbid symptoms, although efficacy is often modest and variable, and side effects can be significant. Adjunctive and investigational approaches targeting glutamatergic and GABAergic neurotransmission, monoaminergic systems, and neuroinflammatory and oxidative stress pathways show preliminary promise but remain experimental. Across all categories, pharmacological treatments are most effective when embedded in individualized, multimodal care plans that integrate behavioral, rehabilitative, and psychological interventions. Conclusions: This review maps pharmacologic strategies in ASD onto their underlying neurobiological mechanisms and clarifies how evidence strength differs across drug classes and symptom domains. Ongoing advances in genetics, synaptic and circuit-level neuroscience, and neuroimmune signaling are expected to yield more specific, mechanism-based pharmacological approaches for autistic behaviors, with the potential to improve long-term functioning and quality of life when combined with comprehensive psychosocial care. Full article

Depression, as a highly prevalent psychiatric disorder, has emerged as a global public health challenge. Its pathological mechanisms involve the cross-regulation of multiple pathways, including neurotransmitter imbalance, neuroinflammation, and oxidative stress. Conventional oral antidepressants are limited in clinical application due to low blood–brain barrier penetration, significant side effects, and restricted therapeutic response rates. In recent years, drug delivery nanosystems (DDNs) have achieved precise regulation and repair of the pathological processes underlying depression through various functional modification strategies, such as targeted conjugation, stimuli responsiveness, and biomimetic simulation. Future efforts should focus on promoting their clinical translation via multi-functional integration, optimization of intelligent response mechanisms, and interdisciplinary collaboration. This review systematically summarizes the major pathogenic pathways of depression, as well as the mechanisms of action and research progress of functionalized DDNs in alleviating depression by targeting and remodeling key pathogenic pathways. It provides theoretical and technical references for the precise treatment of depression and the development of precision medicine for psychiatric disorders. Full article

Cancer remains a major global health challenge, with triple-negative breast cancer (TNBC) representing one of the most aggressive and difficult-to-treat subtypes, characterized by poor prognosis and limited therapeutic options. Current treatments, including chemotherapy, are hindered by high recurrence rates, drug resistance, and severe side effects, highlighting the urgent need for novel therapeutic strategies to address these challenges. Drug repurposing, which involves the application of existing FDA-approved (Food and administration) drugs for new oncological uses, offers a cost-effective and time-efficient alternative to traditional drug development. This review synthesizes recent findings on repurposed drugs, including antidiabetic, antiparasitic, antidepressant, antipsychotic, cardiovascular disease, and non-steroidal anti-inflammatory drugs (NSAIDs), and their potential to target TNBC through mechanisms such as immune modulation, interference with signaling pathways, and inhibition of cancer cell proliferation. Evidence suggests that these agents hold therapeutic promise across heterogeneous TNBC subtypes, although outcomes vary depending on the molecular context. Overall, drug repurposing has emerged as a promising avenue for expanding the treatment options for TNBC; however, further research and personalized approaches are essential to translate these findings into effective clinical applications. Full article

Background: Antidepressant medications are the cornerstone of depression treatment worldwide, playing a central role in reducing the burden of depressive disorders. Their appropriate use is particularly important in low- and middle-income countries (LMICs), where the prevalence of mental health conditions is high and health systems face increasing demand. Despite the clinical importance of antidepressants, limited evidence exists on how psychiatrists in LMICs prescribe these medications. Jordan, a middle-income country with a growing mental health burden, provides a valuable case study for understanding prescribing patterns and identifying areas for improvement. Objectives: This study examined (1) the knowledge, attitudes, and prescribing practices of Jordanian psychiatrists regarding antidepressant medications, and (2) the perceived challenges hindering optimal prescribing. Methods: A mixed-methods design was employed. Quantitatively, a cross-sectional survey was administered to licensed psychiatrists in Jordan (n = 108; response rate 79.4%). The instrument was adapted from previously published tools on psychotropic prescribing practices and refined using international guidelines and recent reviews on antidepressant use. Qualitatively, semi-structured interviews were conducted with a purposive sample of four psychiatrists to explore systemic, clinical, and contextual barriers to antidepressant prescribing. Survey data were analyzed using descriptive statistics and regression analyses, while interview transcripts were subjected to thematic analysis. Results: Although psychiatrists demonstrated a reasonable understanding of antidepressant pharmacology, important gaps were evident. Only one-third (34.3%) recognized Ministry of Health (MOH) guidelines, while nearly four in ten (37.4%) felt international guidelines did not fully apply to Jordan’s population. Laboratory monitoring for metabolic side effects was inconsistently applied, with just 17.6% always requesting such tests and 11.1% never doing so. Consultation with internal medicine for patients on multiple medications was not routine, reported as “sometimes” by 69.4% of psychiatrists. Attitudes toward prescribing reflected caution, particularly in managing pregnant or lactating women, where only half (51.0%) supported discontinuation and three-quarters (75.9%) preferred dose or drug adjustment. Early-career psychiatrists showed lower engagement, as knowledge and attitude scores were significantly higher among those with 11–20 years of experience compared to those with ≤10 years (p < 0.001). Overall, the findings highlight uneven application of evidence-based practices, reliance on personal clinical judgment, and limited engagement with national standards. Conclusions: Although safety and patient outcomes are valued, systemic, clinician, and patient-related barriers constrain optimal practice. Strengthening national guideline dissemination, ensuring medication access, and supporting continuing professional development could improve prescribing practices in Jordan and similar LMIC contexts. Full article

Mirtazapine is an antidepressant used as an appetite stimulant in cats. This study aims to assess owner perspectives on the use of transdermal mirtazapine in cats. A multicentric survey-based study was conducted. A survey of 15 questions about efficacy, side effects, and overall perception was sent to owners of cats that had received the treatment between January 2021 and March 2023 in two European veterinary hospitals. From 108 contacted owners, 70 responses were obtained. Application to the ear was considered easy by 97% of respondents, and 91% followed the manufacturers’ instructions for alternating ears. Side effects were reported by 20%, most often increased vocalization, redness, or restlessness. Chronic kidney disease was the most common reason for prescription. Nine owners had previously used the oral form, and most of them found the transdermal option easier, although some preferred the oral version due to lower cost. Overall, 77% of owners considered the treatment effective in stimulating appetite. Regarding length of therapy, about half administered it for less than 14 days, while the rest followed the labeled duration, with longer use associated with more consistent appetite improvement. These findings highlight that transdermal mirtazapine is generally well accepted by owners, easy to administer, and effective in promoting appetite in cats. Full article

Doxorubicin (DOX) is an effective drug for the treatment of solid tumors and hematological malignancies in both children and adults. The most serious side effect is doxorubicin-induced cardiotoxicity (DIC), which can lead to cardiomyopathy and irreversible and highly fatal cardiac decompensation. The precise mechanisms underlying DIC are not fully understood, and currently, no fully effective preventive or therapeutic strategies exist. Drug repositioning has emerged as a promising approach to mitigate DIC, leveraging existing safety profiles while potentially reducing the time and cost of clinical translation. In this review, we summarize current evidence on drug repurposing for DIC, with a particular focus on the antidepressant paroxetine, which shows potential cardioprotective effects beyond its established role as a selective serotonin reuptake inhibitor (SSRI). Full article

Background/Objectives: A variant of autism spectrum disorder (ASD) known as Asperger syndrome (AS) shows increasing incidence worldwide, affecting between 0.02% and 0.03% of children. Patients display abnormal conduct, are limited in social interaction and communication, and are more often affected by micturition disorders, incontinence, and voiding symptoms than typically developing children. Methods: The present study aimed to review the literature related to the current management of lower urinary tract conditions in children with Asperger syndrome and to present a case of a 14-year-old girl with ASD, with characteristic impairments, including communication challenges, stereotyped, repetitive behaviors, and chronic constipation with concomitant bladder dysfunction, presenting recurrent urinary tract infections (UTIs) and lower urinary tract symptoms (LUTS), including voiding and filling storage symptoms. For the AS, she was treated with a selective serotonin reuptake inhibitor (Sertraline). An abdominal ultrasound, PLUTTS—pediatric lower urinary symptoms scoring (21); QL-quality of life (3); voiding diary; and uroflowmetry were performed, revealing an incomplete urinary retention (incomplete bladder emptying of 120 mL), a prolonged and interrupted curve, a maximum urinary flow rate (Qmax) 7 mL/s, and a UTI with Enterococcus. Results: Besides psychiatric reevaluation and antibiotic therapy, functional magnetic stimulation (FMS) sessions were performed. After eight sessions (20 min, 35 MHz, every second day), the ultrasound control and the uroflowmetry showed no residual urine, and the Qmax was 17 mL/s. The curve continued to be interrupted: PLUTSS-11, QL-1. FMS was continued at two sessions per week. At the 3-month follow-up, no residual urine was detected, and Qmax reached 24 mL/s. Conclusions: ASD is an incapacitating/debilitating condition that significantly impairs social functioning. In many cases, in addition to psychological symptoms, other conditions such as LUTS and constipation may coexist. Antipsychotics and antidepressants are frequently prescribed for these patients, often leading to various side effects, including micturition disorders. Therefore, screening for LUTS is recommended, and, if indicated, treatment—especially non-pharmacological and non-invasive approaches, such as FMS—should be considered. Full article

Background/Objectives: Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus, affecting up to 50% of long-term patients and causing significant pain, reduced quality of life, and healthcare burden. Conventional treatments, including anticonvulsants, antidepressants, and opioids, offer limited efficacy and are associated with adverse effects. Emerging evidence suggests that cannabis, acting via the endocannabinoid system, may provide analgesic and neuroprotective benefits. This study evaluates the long-term effects of inhaled cannabis as adjunctive therapy for refractory painful DN. Inhaled cannabis exhibits rapid onset pharmacokinetics (within minutes, lasting 2–4 h) due to pulmonary absorption, targeting CB1 and CB2 receptors to modulate pain and inflammation. Methods: In this prospective, observational study, 52 patients with confirmed painful DN, unresponsive to at least three prior analgesics plus non-pharmacological interventions, were recruited from a single clinic. Following a 1-month washout, patients initiated inhaled medical-grade cannabis (20% THC, <1% CBD), titrated individually. Assessments occurred at baseline and annually for 5 years, including the Brief Pain Inventory (BPI) for pain severity and interference; the degree of pain relief; Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score; HbA1c; and medication usage. Statistical analyses used repeated-measures ANOVA, Kruskal–Wallis tests, Welch’s t-tests, and Pearson’s correlations via Analyze-it for Excel. Results: Of 52 patients (mean age 45.3 ± 17.8 years; 71.2% male; diabetes duration 23.3 ± 17.8 years), 50 completed follow-up visits. Significant reductions occurred in BPI pain severity (9.0 ± 0.8 to 2.0 ± 0.7, p < 0.001), interference (7.5 ± 1.7 to 2.2 ± 0.9, p < 0.001), LANSS score (19.4 ± 3.8 to 10.2 ± 6.4, p < 0.001), and HbA1c (9.77% ± 1.50 to 7.79% ± 1.51, p < 0.001). Analgesic use decreased markedly (e.g., morphine equivalents: 66.8 ± 49.2 mg to 4.5 ± 9.6 mg). Cannabis dose correlated positively with pain relief (r = 0.74, p < 0.001) and negatively with narcotic use (r = −0.43, p < 0.001) and pain interference (r = −0.43, p < 0.001). No serious adverse events were reported; mild side effects (e.g., dry mouth or euphoria) occurred in 15.4% of patients. Conclusions: Inhaled cannabis showed sustained pain relief, improved glycemic control, and opioid-sparing effects in refractory DN over 5 years, with a favorable safety profile. These findings are associative due to the observational design, and randomized controlled trials (RCTs) are needed to confirm efficacy and determine optimal usage, addressing limitations such as single-center bias and small sample size (n = 52). Future studies incorporating biomarker analysis (e.g., endocannabinoid levels) could elucidate mechanisms and enhance precision in cannabis therapy. Full article

Both neuropathic and nociplastic pain (non-nociceptive pain) are characterized by a similar pattern of clinical symptoms, including numbness, dysesthesia, tingling, and pricking. Whereas nociplastic pain results from altered nociception without indication of tissue damage or a somatosensory system lesion, neuropathic pain is caused by a disease or lesion affecting the somatosensory system. The available therapeutic options consist of antiepileptic drugs, antidepressants, and muscle relaxants. Unfortunately, symptoms are often refractory, and increasing drug dosage may lead to adverse events. In this narrative review, we searched PubMed, MEDLINE, Cochrane, and EMBASE databases from their inception up to 26 July 2025, using the key words “duloxetine,” “pregabalin,” and then ‘‘combination,’’ “nociplastic pain,” “neuropathic pain,” “efficacy,” “safety,” “pharmacology,” “pharmacokinetic,” and “pharmacodynamic.” We evaluated the role of combination therapy with duloxetine, a serotonin–norepinephrine reuptake inhibitor, and pregabalin, an antiseizure medication that acts on voltage-gated calcium channels α2δ subunit, in patients with neuropathic or nociplastic pain. The literature data indicate that combination therapy has synergistic effects, leading to fewer adverse events in specific categories of patients. Available evidence showed that combination therapy is generally not inferior to monotherapy, with slight differences in safety outcomes depending on supplementation, drug labels, and titration. These results indicate that even if not superior, combination therapy may be an alternative to monotherapy in selected patients: those who experience side effects from higher dosages of duloxetine or pregabalin and for whom symptom relief from dose reduction alone is not possible; those who use medications that interact with duloxetine; those who suffer from anxiety–depression, where pain is closely linked to mental symptoms; and those who have central neuropathic pain (often refractory). Full article

Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article

Insomnia is a common and complex disorder, rooted in the dysregulation of circadian rhythms, impaired neurotransmitter function, and disturbances in sleep–wake homeostasis. While conventional hypnotics such as benzodiazepines and Z-drugs are effective in the short term, their use is limited by a high potential for dependence, cognitive side effects, and withdrawal symptoms. In contrast, melatonergic receptor agonists—melatonin, ramelteon, tasimelteon, and agomelatine—represent a pharmacologically targeted alternative that modulates MT1 and MT2 receptors, which are pivotal to the regulation of circadian timing and sleep initiation. Clinical evidence supports the efficacy of these agents in reducing sleep onset latency, extending total sleep duration, and re-aligning disrupted circadian rhythms, particularly among older individuals and patients with non-24 h sleep–wake disorders. Notably, agomelatine offers additional antidepressant properties through selective antagonism of the 5-HT_2C receptor in micromolar concentrations. In contrast, its agonistic activity at melatonergic receptors is observed in the low sub-nanomolar range, which illustrates the complexity of this drug’s interactions with the human body. All compounds reviewed demonstrate a generally favorable safety and tolerability profile. Accumulating evidence highlights that selected medicinal plants, such as chamomilla, lemon balm, black cumin, valeriana, passionflower and lavender, may exert relevant hypnotic or anxiolytic effects, thus complementing melatonergic strategies in the management of insomnia. This structured narrative review presents a comprehensive analysis of the molecular pharmacology, receptor affinity, signaling pathways, and clinical outcomes associated with melatonergic agents. It also examines their functional interplay with serotonergic, GABAergic, dopaminergic, and orexinergic systems involved in arousal and sleep regulation. Through comparative synthesis of pharmacokinetics and neurochemical mechanisms, this work aims to inform the development of evidence-based strategies for the treatment of insomnia and circadian rhythm sleep–wake disorders. Full article

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are among the leading causes of disability worldwide and are frequently associated with treatment resistance, functional impairment, and high comorbidity with metabolic dysfunction. Increasing evidence implicates insulin resistance (IR) as a key pathophysiological factor linking metabolic and psychiatric illness. IR is associated with chronic low-grade inflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, impaired neuroplasticity, mitochondrial dysfunction, and altered reward processing mechanisms that may contribute to core depressive features such as anhedonia, cognitive slowing, and emotional dysregulation. These processes are further exacerbated by the metabolic side effects of many psychotropic medications, creating a self-perpetuating cycle that worsens both psychiatric and physical health outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes and obesity, have emerged as promising candidates to address this metabolic–psychiatric interface. Beyond improving glycemic control and promoting weight loss, GLP-1 RAs exert central actions relevant to mood disorders, including modulation of dopaminergic reward pathways, enhancement of hippocampal neurogenesis, attenuation of neuroinflammation, and regulation of appetite and energy balance. Preclinical studies demonstrate that GLP-1 RAs reduce microglial activation, promote hippocampal neurogenesis, and normalize stress-induced behavioral changes. Early clinical trials in patients with metabolic disorders suggest improvements in depressive symptoms, quality of life, and cognitive function, with some effects independent of weight loss or glycemic outcomes. Observational evidence also indicates reduced antidepressant use and psychological distress in diabetic and obese populations receiving GLP-1 RAs. While these findings are promising, large randomized controlled trials in primary psychiatric populations are lacking. Key challenges include clarifying dose–response relationships, disentangling central from peripheral effects, and addressing safety and adherence concerns in individuals with comorbid psychiatric conditions. Future research should focus on biomarker-informed stratification, comparative trials with standard treatments, and integration of GLP-1 RAs into multimodal care frameworks. Overall, GLP-1 RAs represent a biologically plausible and clinically relevant approach to bridging metabolic and psychiatric care, with the potential to improve outcomes in patients with mood disorders who carry a high metabolic burden. Full article