Search Results (67)

Background: Serotonin (5-HT) is a neurotransmitter and a hormone that regulates various functions. Serotonin receptors have been studied in animal experiments in the vestibular system, beginning from the inner ear and vestibular nuclei. However, the role of serotonin in the vestibular system and disorders remains to be clarified. Methods: A review of the literature was performed on different databases according to the PRISMA guidelines. Only publications published on humans and in English have been included. A total of 41 articles were included in this review. Results: There are many publications regarding the use of SSRI/SNRI in vestibular disorders. Regarding persistent postural perceptual dizziness (PPPD) and chronic subjective dizziness (CSD) the available evidence supports multimodality treatment incorporating vestibular rehabilitation, serotonergic medications, and cognitive behavior therapy, although most studies have not included a placebo control group. As for vestibular migraine (VM), SNRI and SSRIs were proposed as preventive therapy and demonstrated a reduction in vertigo attacks in patients with Menière’s Disease (MD), especially when symptoms of anxiety disorder were present. Conclusions: Although SSRIs/SNRIs are considered an off-label therapy for vertigo, several studies have assessed their efficacy in vestibular disorders, as indicated in the data published on PPPD, MD, and VM above all. As some studies report that serotonin receptors are also present in the inner ear and vestibular nuclei, it can be postulated that in cases where the natural levels of serotonin are altered, such as in depression and anxiety, the change in serotonin levels may affect vestibular function and play a role in vestibular disorders. Full article

Chronic pain is a serious health issue, often irrationally managed by conventional analgesics. Duloxetine, a serotonin–norepinephrine reuptake inhibitor (SNRI), also effective in neuropathic and musculoskeletal pain, but the molecular mechanism of its analgesic action is still unclear. Here, we examined whether Duloxetine exerts pleiotropic effects by directly targeting phosphorylated STAT3 (pSTAT3), a key regulator of neuroinflammation and pain sensitization. Molecular docking showed that Duloxetine binds with pSTAT3 with binding energy −5.83 kcal/mol. Ruxolitinib, a JAK/STAT inhibitor used as reference, showed binding energy of −6.19 kcal/mol. Molecular dynamics (MD) simulations confirmed stable Duloxetine–pSTAT3 complexes, while MM-PBSA free energy analysis revealed more favorable binding for Duloxetine (ΔG = −15.17 kJ·mol⁻¹) than Ruxolitinib (ΔG = −12.98 kJ·mol⁻¹) for pSTAT3. In-vitro analyses, Western blot showed that Duloxetine significantly reduced IL-6–induced STAT3 and pSTAT3 expression in C2C12 cells in a dose-dependent manner (6.4 and 12.8 μM, *** p < 0.0001), although Ruxolitinib produced a stronger suppression. Transcriptomic analysis revealed Duloxetine-specific enrichment of mitochondrial, oxidative phosphorylation, and synaptic pathways, distinct from the immune-suppressive influence of Ruxolitinib. RNA-seq further revealed that STAT3 transcript abundance remains constant under all treatment conditions, indicating that post-transcriptional or post-translational mechanisms, such as phosphorylation-dependent activation, may be involved rather than transcriptional modulation of STAT3 in action of Ruxolitinib and Duloxetine and the formation of novel STAT3 indicating enhanced transcript diversity. The rMATS splicing analysis confirmed dose-dependent modulation, with Duloxetine promoting mild exon skipping at 6.4 μM (IncLevel 0.90 → 0.80) and recovery at 12.8 μM (0.85 → 0.86), while Ruxolitinib induced stronger exon inclusion (0.85 → 1.00,0.94), with broader transcript suppression at 6.4 μM and 12.8 μM, respectively. These findings establish Duloxetine as a dual-action therapeutic that combines neurotransmitter reuptake inhibition with pSTAT3 suppression and isoform-level transcriptomic modulation. This pleiotropic mechanism provides a rationale for its durable analgesic effects and supports repurposing in STAT3-associated disorders. Full article

Traditional risk models often fail to capture extreme losses in interconnected global stock markets. This study introduces a novel approach, Expectile Regression Neural Network with Modified LASSO regularization (ERNN-mLASSO), to model nonlinear systemic risk. By analyzing five major stock indices (JKSE, GSPC, GDAXI, FTSE, N225), we identify distinct market roles: developed markets, such as the GSPC, act as risk spreaders, while emerging markets, like the JKSE, act as risk takers. Our network systemic risk index, SNRI, accurately captures systemic shocks during the COVID-19 crisis. More importantly, the model projects increasing global financial fragility through 2025, providing an early warning signal for policymakers and risk managers of potential future instability. Full article

Opioids and benzodiazepines (BZD) are commonly prescribed for older cancer survivors with co-occurring pain and anxiety. The prescribing rate of gabapentinoids (GABA), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) in the general population has increased as opioid/BZD alternatives, but little is known on temporal/regional trends in use of these alternatives among older cancer survivors. A retrospective cohort study using SEER-Medicare data was conducted. Patients aged ≥ 66 years, diagnosed with breast, colorectal, prostate, or lung cancer as their first cancer diagnosis any time from 2000 to 2015 and who were alive more than 5 years after cancer diagnosis, were eligible for inclusion. Temporal trends varied by region (p < 0.0001) and opioid-naïve status (p < 0.0001). Compared to 2013, GABA and SNRI use increased, while BZD and opioid use decreased. All regions experienced declines in opioid use. From 2013 to 2018, all regions saw an increase in GABA use, with a decline in 2020. GABA prescriptions increased more in opioid-naïve groups compared to non-opioid-naïve patients. The yearly trends in GABA and SSRI/SNRI use varied by region among older cancer survivors. Clinical practice variation suggests needs for further research on improving consistency and quality of cancer care. Full article

Herbal medicinal products are increasingly used alongside conventional medicines, raising the risk of potential interactions such as pharmacodynamic drug–herb interactions (PD-DHIs) that can cause serious adverse drug reactions (ADRs). This review aims to present available pharmacological, clinical and pharmacoepidemiological literature regarding potential DHIs associated with serotonin syndrome or cardiac arrhythmias. Furthermore, it assesses the current evidence using the Oxford Centre for Evidence-Based Medicine (CEBM) 2009 framework. Serotonin syndrome most often results from combining serotonergic herbs (e.g., St. John’s wort) with antidepressants like serotonin reuptake inhibitors (SSRIs), as supported by repeated case reports and mechanistic plausibility (CEBM Level 3, Grade C). Other herbs such as black cohosh, ginseng, Syrian rue, turmeric, rhodiola, ashwagandha, and L-tryptophan/5-HTP have been linked to serotonin syndrome when used with SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), but evidence is limited (Levels 4–5, Grade D). For cardiac arrhythmias, PD-DHIs arise when herbs interact with drugs that alter cardiac electrophysiology—such as QT-prolonging agents, psychotropics, antiarrhythmics or digoxin—thereby amplifying arrhythmogenic risk. Ephedra with sympathomimetics is strongly associated with arrhythmias (Level 2–3, Grade B). Licorice may potentiate digoxin and QT-prolonging drugs via hypokalemia (Level 4, Grade C). Other related PD-DHIs include aconite with antiarrhythmics, bitter orange or caffeine with QT-prolonging psychotropics, yohimbine with cardiovascular agents, and aloe or senna with digoxin. Overall, the evidence for PD-DHIs varies from moderate to weak but large-scale pharmacoepidemiological data is scarce. Future approaches, including artificial intelligence with explainable machine learning and network pharmacology, may integrate mechanistic, clinical, and real-world data to improve early detection or prediction of PD-DHIs. However, several specific challenges must be addressed. Therefore, it is crucial for healthcare providers in both clinical and community settings to increase their awareness of these interactions and ADRs to ensure the safe use of herbal remedies alongside conventional therapies. Full article

Anxiety and depression are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which can contribute to increased morbidity, reduced quality of life, and worse clinical outcomes. Nevertheless, these psychological conditions remain largely overlooked. This narrative review includes studies published between 1983 and 2025 to synthesise the current evidence on the risk factors, clinical impacts, and therapeutic strategies for these comorbidities. While the exact mechanisms leading to their increased prevalence are not fully understood, growing evidence implicates a combination of biological (e.g., systemic inflammation), social (e.g., isolation and stigma), and behavioural (e.g., smoking and inactivity) factors. Despite current guidelines recommending the identification and management of these comorbidities in COPD, they are not currently included in COPD assessments. Undetected and unmanaged anxiety and depression have serious consequences, including poor self-management, non-adherence to medications, increased risk of exacerbation and hospitalisations, and even mortality; thus, there is a need to incorporate screening as part of COPD assessments. There is robust evidence showing that pulmonary rehabilitation, a core non-pharmacological intervention, can improve mood symptoms, enhance functional capacity, and foster psychosocial resilience. Psychological therapies such as cognitive behavioural therapy (CBT), mindfulness-based approaches, and supportive counselling have also demonstrated value in reducing emotional distress and improving coping mechanisms. Pharmacological therapies, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed in moderate to severe cases or when non-pharmacological approaches prove inadequate. However, the evidence for their efficacy in COPD populations is mixed, with concerns about adverse respiratory outcomes and high discontinuation rates due to side effects. There are also barriers to optimal care, including underdiagnosis, a lack of screening protocols, limited provider training, stigma, and fragmented multidisciplinary coordination. A multidisciplinary, biopsychosocial approach is essential to ensure early identification, integrated care, and improved outcomes for patients with COPD. Full article

Depression in cancer survivors is commonly treated with serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine. These drugs alleviate depressive symptoms by inhibiting the reuptake of serotonin and norepinephrine. However, a novel approach has emerged with the development of trans-2-phenylcyclopropylamine (PCPA)–drug conjugates that inhibit lysine-specific demethylase 1 (LSD1), which is a biomarker and molecular target for cancer therapy. LSD1 inhibition can effectively suppress cancer cell proliferation. Nuc01 is a novel PCPA–drug conjugate designed as a prodrug of venlafaxine. In vivo studies showed that Nuc01 dose-dependently reduced immobility time in the tail suspension test in mice, outperforming desmethylvenlafaxine. This suggests that Nuc01 may act as a potent triple reuptake inhibitor, potentially offering enhanced efficacy in the treatment of depression. Additionally, in vitro studies demonstrated that Nuc01 effectively occupies the PCPA binding site within LSD1 (IC₅₀ = 530 nm) and inhibits the proliferation of MDA-MB-231 cancer cells (IC₅₀ = 1130 nm). These findings suggest that Nuc01 may function as an LSD1 inhibitor with potential anticancer properties. Collectively, the data indicate that Nuc01 appears to exhibit dual functional characteristics: acting as a triple reuptake inhibitor potentially applicable for depression treatment and as an LSD1 inhibitor demonstrating anticancer potential. Full article

Rolling bearing fault diagnosis in electric hoists faces significant challenges due to heavy noise and complex vibration interferences, which obscure fault signatures and hinder conventional demodulation methods. While existing techniques like the Teager–Kaiser energy operator (TKEO) and its variants (e.g., HO-AEO, SD-AEO) offer filterless demodulation, their susceptibility to noise and dependency on preprocessing limit diagnostic accuracy. This study proposes a Multi-resolution Higher-order Symmetric Analytic Energy Operator (MHSAEO) to address these limitations. The MHSAEO integrates three innovations: (1) dynamic non-adjacent sampling to suppress stochastic errors, (2) AM-FM dual demodulation via symmetric energy orthogonality, and (3) adaptive spectral mining for full-band feature extraction. Experimental validation on a 10-ton electric hoist bearing system demonstrates that the MHSAEO achieves signal-to-noise ratio improvements (SNRIs) of −3.83 dB (outer race faults) and −2.12 dB (inner race faults), successfully identifying the characteristic fault frequencies of both inner (145.9 Hz) and outer races in electric hoist bearings with 2nd–5th harmonics. Compared to traditional methods, the MHSAEO reduces computational time by 30.1 × (0.0328 s vs. 0.9872 s) without requiring preprocessing. The results confirm its superior anti-interference capability and real-time performance over the TKEO, HO-AEO, and hybrid denoising–TKEO approaches. Full article

Background/Objectives: Depression ranks among the most prevalent mental health conditions globally, marked by a variety of symptoms that frequently cause significant emotional distress and impairment in individuals, alongside a high recurrence rate. The predominant approach to treating depression revolves around monoamine theory, utilizing SSRIs and SNRIs, with Esketamine emerging as a supplementary option in recent times. Nevertheless, there is a growing focus on exploring the relationship between inflammation and depression, revealing a strong correlation between the two. This insight prompts consideration of the anti-inflammatory properties of current antidepressants in their therapeutic application. Methods: A systematic literature search was conducted using the PubMed database to identify randomized controlled trials (RCTs) and clinical trials (CTs) that assessed the in vivo anti-inflammatory effects of SSRIs (fluoxetine, escitalopram, sertraline, and paroxetine), the SNRI venlafaxine, and esketamine/ketamine in human subjects undergoing treatment for depression. The included studies were evaluated based on changes in levels of pro-inflammatory and anti-inflammatory markers in response to the antidepressant treatments. Results: SSRIs, SNRIs, esketamine, and ketamine (a racemic mixture of S- and R-ketamine not formally approved for the treatment of depression) exhibit anti-inflammatory effects through diverse mechanisms, such as reducing pro-inflammatory cytokines or enhancing anti-inflammatory cytokines in serum or within specific brain regions like the hippocampus and prefrontal cortex. These actions are mediated through various inflammatory pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome, the glutamatergic system, the gut–brain axis, the hypothalamic–pituitary axis, impaired neuroplasticity, and the kynurenine pathway. Conclusions: In summary, SSRIs, SNRIs, esketamine, and ketamine exert an anti-inflammatory role alongside their antidepressant effects via these intricate mechanisms. Full article

Background: Mixed urinary incontinence (MUI), particularly the urge-predominant subtype, involves both stress urinary incontinence (SUI) and urge urinary incontinence (UUI), posing a therapeutic challenge. Duloxetine, a serotonin–norepinephrine reuptake inhibitor (SNRI), enhances urethral tone, while tolterodine, an antimuscarinic agent, reduces detrusor overactivity. Their combination may offer synergistic benefits. Aim: The aim of this study was to evaluate the efficacy of duloxetine and tolterodine combination therapy in urge-predominant MUI and identify factors influencing treatment success. Method: A retrospective study was conducted on 106 patients (mean age: 56.45 years) with urge-predominant MUI treated with duloxetine (40 mg twice daily) and tolterodine (4 mg once daily) for 12 weeks. Treatment outcomes were evaluated using the overactive bladder symptom score (OABSS), International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), 24 h pad test, and Clinical Global Impression Scale (CGI). Univariate and multivariate regression analyses were performed to determine predictors of success. Results: Significant improvements were observed: OABSS decreased from 11.08 to 6.95, ICIQ-SF decreased from 15.69 to 8.84, and pad use decreased from 3.58 to 0.73/day (all p 0.0001). Bladder capacity increased from 315.09 mL to 436.32 mL. Baseline ICIQ-SF scores were independent predictors of success (odds ratio [OR] = 2.919, p = 0.001). Patient satisfaction reached 77.4%, with mild side effects (constipation and dizziness) in 14 patients. Conclusions: Duloxetine and tolterodine combination therapy significantly improved symptoms and quality of life in urge-predominant MUI. Baseline ICIQ-SF scores may predict treatment success. Further prospective studies are needed. Full article

Background: Depression is one of the leading causes of disability worldwide. Among pharmacological treatments, fluvoxamine—an early SSRI with a distinct pharmacological profile—has been recently reappraised for its broader clinical relevance. Objective: To assess the efficacy of fluvoxamine in the treatment of depression compared to placebo and other antidepressants through a comprehensive overview of systematic reviews and meta-analyses. Methods: A systematic search was conducted in MEDLINE and the Cochrane Central Register of Controlled Trials, including systematic reviews and meta-analyses of randomized controlled trials evaluating fluvoxamine’s efficacy. Reviews were eligible if they included adults diagnosed with depressive disorders based on the DSM or ICD criteria. Reviews focusing on other psychiatric disorders, comorbidities, tolerability, or economic evaluations were excluded. Data extraction included effect size measures and methodological quality assessments using the AMSTAR-2 tool. Results were synthesized by comparing fluvoxamine to placebo, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and other antidepressants. Results: A total of 74 reviews were identified, of which 14 systematic reviews met the inclusion criteria after screening and full-text analysis. These reviews, published between 1994 and 2021, predominantly involved nine pairwise meta-analyses and five network meta-analyses, comparing fluvoxamine with placebo and various antidepressants. Fluvoxamine demonstrated consistent superiority over placebo in achieving treatment response and remission outcomes. Comparisons with imipramine, clomipramine, amitriptyline, dothiepin, paroxetine, fluoxetine, citalopram, mianserin, nortriptyline, and moclobemide generally revealed no significant differences in efficacy. However, some reviews indicated that venlafaxine and mirtazapine were superior to fluvoxamine in certain outcomes, while fluvoxamine demonstrated greater efficacy than desipramine in one review. Sertraline and milnacipran showed mixed or review-quality-dependent results, with one low-quality review favoring milnacipran. Most reviews assessed outcomes over a median follow-up of six weeks using standardized depression rating scales. Conclusions: Fluvoxamine is a robust and effective antidepressant, demonstrating consistent efficacy comparable to other antidepressants and superior to placebo. While no single antidepressant was universally superior, fluvoxamine’s unique pharmacological profile and favourable safety characteristics support its clinical utility. Further research is needed to explore its role in personalized treatment strategies and emerging therapeutic contexts, such as comorbid anxiety and post-traumatic stress disorder. Full article

Background/Objectives: Venlafaxine (VEN) is a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant. Arterial hypertension (HTN), heart failure (HF), and arrhythmias are side effects of VEN. Cardiotoxicity (CTOX) as a feature of VEN-associated side-effects has only rarely been described. Methods: We conducted a search of our database for cases of VEN-associated CTOX, analyzing symptoms, echocardiographic findings, and laboratory results. Results: We identified five patients (three females, two males) with VEN-associated CTOX, aged 51 to 87 years at presentation. VEN dose was 150 and 375 mg daily and treatment duration was 1.5 to 15 years. Presenting features were HTN in three, “hypertrophic cardiomyopathy” in two, heart failure in three, and atrial fibrillation in three patients. Symptoms and signs of CTOX were reversible in all patients after discontinuation or dose reduction of VEN, suggesting a causal relationship between VEN and CTOX. Conclusions: VEN-associated CTOX can occur and progress to severe cardiomyopathy or heart failure. Potential risk factors include cardiac sympathetic stimulation, high VEN dosage, and prolonged treatment duration; however, CTOX may also occur at standard doses. Therefore, patients taking VEN should be routinely monitored for signs of cardiotoxicity, including monitoring of serum concentrations of VEN. Full article

Objective: This study assessed the utility of capillary blood cartridge-based analysis in evaluating neonatal jitteriness (NJ). Methods: In this retrospective study, we compared outcomes between neonates (37–41 weeks of gestation) diagnosed with neonatal jitteriness (NJ) within the first 72 h of life and a control group of healthy neonates (GA 37–41 weeks) with an uneventful perinatal course and no signs of jitteriness. Results: Each group included 101 neonates. Jittery neonates had a higher proportion of males (70.3% vs. 50.5%, p = 0.004), a lower mean gestational age (38.8 vs. 39.2 weeks, p = 0.002), and a higher rate of emergency cesarean deliveries (14.9% vs. 3.0%, p = 0.003). The logistic regression identified male sex (OR = 2.5, p = 0.007) and in utero selective serotonin reuptake inhibitor (SSRI) exposure (OR = 9.0, p = 0.005) as significant risk factors for NJ. The capillary blood parameters, except glucose levels, did not differ significantly between the neonates admitted to the NICU and those discharged. Hypoglycemic jittery neonates were 10 times more likely to require NICU admission compared to their non-hypoglycemic counterparts (OR = 10.9, 95% CI: 2–59.5, p = 0.006). Conclusions: Point-of-care glucose testing using a bedside glucometer may be sufficient for the evaluation of neonatal jitteriness, as capillary blood cartridge-based testing did not offer an additional diagnostic value. What is Known: NJ is often viewed as a self-resolving benign phenomenon; however, in certain cases, it can be an indicator of an underlying pathology. There is substantial evidence linking the maternal use of SSRIs or SNRIs during pregnancy with the occurrence of NJ in newborns as well as an association between hypoglycemia and NJ. What is New: This study is the first to evaluate the clinical utility of systematic capillary blood cartridge-based testing in jittery neonates using a relatively large cohort. Male neonates were disproportionately represented among cases of NJ. Healthy neonates with jitteriness had normal electrolytes, with hypoglycemia as the only concern. A glucometer test may suffice for evaluation, but those who are small for their gestational age or have initial hypoglycemia require a routine follow-up due to a higher risk of NICU admission. Full article

Objective: To narratively review currently available antidepressants and future potential antidepressants as monotherapy for the treatment of depressive disorders. Methods: Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), dopamine reuptake inhibitor (bupropion), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) were reviewed according to the results from Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study and systematic reviews. For the rest of the antidepressants, a PubMed/Medline search was conducted with priority for systematic reviews. For drugs in development for depressive disorders, PubMed, Google, and Clinicaltrials.gov databases were used. Results: The STAR*D Study demonstrated that sertraline, venlafaxine, and bupropion monotherapy had similar efficacy in patients with major depressive disorder (MDD) who failed citalopram. A network meta-analyses of randomized, placebo-controlled trials found that SSRIs, SNRIs, bupropion, TCAs, mirtazapine, and agomelatine had similar relative efficacy compared to placebo, but had different acceptability. Gepirone had more failed/negative studies and smaller effect size relative to placebo compared to other antidepressants. The combination of dextromethorphan and bupropion, ketamine infusion, and intranasal esketamine had faster onset of action but similar effect size compared to monoamine-based antidepressants as monotherapy. Brexanolone and zuranolone are effective in postpartum depression (PPD), but the effect size of zuranolone in MDD as monotherapy or adjunctive therapy was very small. Psychedelics, glutamate receptor-related agents, kappa opioid receptor antagonists, orexin receptor antagonists, new anti-inflammatory agents, and biomarker-based antidepressant therapy have been under investigation for depressive disorders. Psychedelics showed faster onset of action, large effect size, and long durability. Conclusions: Monoamine-based antidepressants likely continue to be the mainstream antidepressants for depressive disorder. NMDA receptor antagonists and neurosteroid antidepressants will play a bigger role with the improvement of accessibility. Psychedelics may become a game changer if phase III studies validate their efficacy and safety in depressive disorders. Full article

Background: Antidepressants such as SSRIs and SNRIs are widely prescribed; however, significant concerns exist regarding psychiatric adverse drug reactions (ADRs), particularly suicidal ideation, suicide attempts, and completed suicides. This study analyzes pharmacovigilance (PhV) data from the EudraVigilance database to assess the frequency of psychiatric ADRs, including suicide-related events, associated with six commonly used antidepressants. Another aim of the study is to evaluate the utility of pharmacovigilance data in providing insights into real-world risks associated with medications, highlighting the importance of improving the ADR reporting system and ensuring the completeness and reliability of ADR reports. Methods: Data from December 2001 to September 2024 were analyzed for duloxetine, citalopram, escitalopram, fluoxetine, venlafaxine, and sertraline. Reports were categorized by age, gender, and source, focusing on psychiatric ADRs and suicide-related events, including completed suicides and suicide attempts. Results: Psychiatric ADRs accounted for a substantial portion of total reported ADRs for the studied antidepressants, ranging from 33.9% to 38.2%. Venlafaxine had the highest count of psychiatric ADRs (13,134 cases), with duloxetine showing the highest relative percentage (38.2%). Completed suicides were most frequent with venlafaxine (1635 cases), while the highest percentage relative to total ADRs was observed for fluoxetine and citalopram (6%). ADRs occurred more frequently in women, particularly for duloxetine (67%) and sertraline (61.3%), and suicide attempts were prevalent in patients aged 18–64, with notable incidence in the 0–17 age group. Conclusions: This study highlights the significant patterns, risks, and underreporting of psychiatric ADRs associated with commonly prescribed antidepressants. Using EudraVigilance data and a worst-case scenario approach, it reveals the extent of suicide-related ADRs, age and gender disparities, and the impact of incomplete reporting on risk assessment. Full article