Search Results (50)

Background/Objectives: Concerns regarding the psychiatric safety profile of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have increased since the 2023 European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) reviews. However, it remains unclear whether this signal is uniform across the drug class or concentrated in specific compounds. This study aimed to characterize and compare, in a systematic manner, the global reporting patterns of psychiatric adverse drug reactions (ADRs) associated with the main GLP-1 RAs using the World Health Organization (WHO) VigiBase global pharmacovigilance database. Methods: A descriptive, cross-sectional pharmacovigilance study was conducted on individual case safety reports (ICSRs) retrieved from VigiAccess (January 2000–2026) for semaglutide, liraglutide, dulaglutide, exenatide, tirzepatide, and lixisenatide. A disproportionality analysis was performed within the MedDRA “Psychiatric disorders” System Organ Class (SOC) using the Reporting Odds Ratio (ROR) with 95% confidence intervals (CIs). This study adhered to the STROBE and READUS-PV guidelines. Results: A total of 537,519 ADR reports were analyzed across the five drugs with sufficient reporting volume (lixisenatide was excluded owing to n = 22 psychiatric events). Psychiatric disorders accounted for 24,899 reports, with marked intraclass heterogeneity in both the proportion of psychiatric reports (6.73% for semaglutide versus 3.12% for tirzepatide) and in disproportionality estimates. Signals of disproportionate reporting were identified exclusively for semaglutide (ROR 1.55; 95% CI 1.50–1.59) and liraglutide (ROR 1.19; 95% CI 1.15–1.23), whereas tirzepatide, dulaglutide, and exenatide showed point estimates below unity. Conclusions: The psychiatric safety profile of GLP-1 RAs is not homogeneous within the therapeutic class. The disproportionality signal is concentrated on semaglutide and, to a lesser extent, liraglutide. These findings extend previous WHO-based analyses limited to suicidality and support active clinical surveillance of psychiatric symptoms in patients treated with these specific agents. Full article

Background: Personalized precision medicine adapts therapeutic strategies to individual characteristics. In psychiatry, suboptimal outcomes with antipsychotics are often related to adverse drug reactions, poor adherence and therapeutic failure. Pharmacogenetics, particularly CYP2D6 genotyping, can improve clinical outcomes through genotype-guided therapy. This study aimed to design and implement a pharmacogenomic and pharmacokinetic testing program for long-acting injectable (LAI) antipsychotics within the Galician Health Service to enhance personalized psychiatric care. Methods: The pilot program encompasses pharmacogenetic and pharmacokinetic testing. Inclusion criteria were broad, covering patients initiating or receiving LAI antipsychotic therapy, as well as those with prior adverse reactions in order to explore scenarios where pharmacogenetic and/or pharmacokinetic data could help with clinical decisions. Structured workflows, interdisciplinary training and integration of results into the electronic health record supported implementation. A pharmacogenetic panel was specifically designed for psychiatric care, targeting clinically relevant variants in CYP2D6, CYP3A4 and ABCB1. Results: A total of 540 patients were included, with primary testing reasons being clinical follow-up (54.6%) and oral-to-LAI transition (38.5%). The CYP2D6 phenotypes were 55% normal, 34% intermediate, 6.3% poor and 4.3% ultrarapid metabolizers. Atypical metabolism was observed in 6.7% of patients for CYP3A4 and in over half for ABCB1. Plasma drug levels were within the therapeutic range for most patients, though some measurements were above or below expected values. Conclusions: This pilot demonstrates a scalable, evidence-based approach to precision psychiatry for LAI antipsychotics, integrating pharmacogenetic and pharmacokinetic testing into routine care. The framework facilitates genotype-guided decision-making and supports broader adoption of pharmacogenomics in psychiatric practice. Full article

Background/Objectives: Fluoroquinolones (FQNs) are widely prescribed broad-spectrum antibiotics but are associated with central and peripheral nervous system adverse reactions (ARs). Regulatory agencies have issued multiple safety warnings regarding their neuropsychiatric effects; however, large-scale, comparative evaluations across individual FQNs remain limited. This study aimed to comprehensively characterise and compare neuropsychiatric profiles associated with Ciprofloxacin, Levofloxacin, and Moxifloxacin using pharmacovigilance data. Methods: A retrospective pharmacovigilance study was conducted using reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between 2010 and 2025. Neuropsychiatric ARs were identified using MedDRA terms, including neurological and psychiatric manifestations. Reporting trends, demographic characteristics, and event frequencies were descriptively analysed. Signal detection was performed using the Information Component (IC), Proportional Reporting Ratio (PRR), and Reporting Odds Ratio (ROR). Results: A total of 95,968 individual case safety reports involving neuropsychiatric ARs were included. Levofloxacin accounted for the highest number of reported events, followed by Ciprofloxacin and Moxifloxacin. Disproportionality analyses identified peripheral neuropathy as the strongest neurological signal for Levofloxacin and Moxifloxacin, while Ciprofloxacin showed stronger central nervous system associations. Psychiatric ARs were drug-specific, with anxiety predominating for Ciprofloxacin and Moxifloxacin, and insomnia for Levofloxacin. All major signals were statistically robust (IC025 > 0), confirming distinct compound-specific neuropsychiatric risk profiles. Conclusions: The large-scale 16-year analysis demonstrates distinct, drug-specific neuropsychiatric risk profiles. The available evidence supports a non-interchangeable safety profile among FQNs and emphasises the importance of drug-specific risk–benefit assessment in clinical practice. Full article

Background/Objectives: Finasteride and dutasteride are 5α-reductase inhibitors that block the conversion of testosterone to dihydrotestosterone, reducing androgenic stimulation of tissues such as the prostate and hair follicles. Used mainly for benign prostatic hyperplasia and androgenic alopecia, finasteride selectively inhibits type-2 5α-reductase isoenzyme, while dutasteride inhibits both type-1 and type-2. Although sexual adverse effects like erectile dysfunction are well-documented, emerging evidence suggests possible neuropsychiatric reactions—including depression, suicidal ideation, and cognitive decline—potentially linked to reduced neurosteroid synthesis, such as that of allopregnanolone. Causality cannot be inferred from spontaneous reporting data. This study aimed to assess pharmacovigilance signals for psychopathological disorders associated with finasteride and dutasteride in the FAERS database. Methods: Cleaned FAERS data referring to years up to 2025 after deduplication were analyzed, excluding non-serious cases and those without the drug as the sole suspect (MedDra 29.0). Reporting Odds Ratios (RORs) with 95% CIs were calculated to compare psychiatric reactions between finasteride and dutasteride. Python 3.11 was used to screen and summarize relevant cases, accounting for differences in total case numbers. Results: This pharmacovigilance study analyzed FAERS data to assess the neuropsychiatric and sexual adverse reactions associated with finasteride and dutasteride. Depression, anxiety, suicidality, and libido-related issues were reported more frequently for finasteride, especially in younger men using low-dose therapy for alopecia. Potential mechanisms include reduced neurosteroid synthesis, androgen/sex-hormone axis disruption, altered hippocampal neurogenesis, and dopaminergic changes. Conclusions: A baseline psychiatric assessment and the regular monitoring of mood, sexual function, and suicidal ideation are recommended. Limitations include under-reporting, reporting bias, and a lack of incidence data. The findings underscore the need for ongoing surveillance and controlled studies to clarify the clinical significance of these signals. Full article

Purpose: Bortezomib (BTZ) is widely used in multiple myeloma (MM), but its toxicity shows marked interindividual variability. This study aimed to identify pharmacogenetic and clinical factors associated with BTZ-related adverse drug reactions (ADRs). Methods: A retrospective and prospective observational study was conducted in 127 MM patients treated with BTZ-based regimens. Polymorphisms in CYP enzymes and ABCB1 were genotyped using qPCR. Associations between genetic variants, treatment response, and ADRs were assessed using univariate and multivariate analyses with Benjamini–Hochberg correction. Results: ADRs occurred in 98.4% of patients, most commonly gastrointestinal toxicity (49%), general toxicity (46%), and peripheral neuropathy (39%). Women showed higher rates of gastrointestinal toxicity and non-peripheral neurotoxicity. Multivariate analysis identified the ABCB1 C1236T A/G genotype as protective against gastrointestinal toxicity, while the CYP3A4 intermediate metabolizer phenotype was associated with increased psychiatric toxicity. TP53 mutations were independently associated with hematologic and renal toxicity. Kaplan–Meier analysis showed earlier onset of peripheral neuropathy and respiratory toxicity in CYP3A4 intermediate and poor metabolizers. Conclusions: Genetic variation in ABCB1 and CYP3A4, together with clinical factors such as TP53 mutation and sex, may contribute to interindividual variability in BTZ safety in MM. These findings should be considered exploratory given the sample size and require confirmation in larger cohorts. Nonetheless, they suggest a potential role for pharmacogenomics in supporting future approaches to treatment personalization. Full article

Background: Biological sex contributes to variability in drug metabolism, receptor sensitivity, and susceptibility to adverse drug reactions (ADRs). Despite this, dosing recommendations for selective serotonin reuptake inhibitors (SSRIs) and second-generation antipsychotics (SGAs) are still largely sex-neutral. This systematic review examines sex-related differences in pharmacokinetics (PK), pharmacodynamics (PD), and safety outcomes, with the aim of clarifying their potential implications for personalized psychopharmacology. Methods: A systematic search of PubMed was conducted for studies published between January 2010 and March 2026. The strategy combined MeSH terms and free-text keywords related to SSRIs, SGAs, sex differences, pharmacokinetics, pharmacodynamics, and ADRs. Two independent reviewers performed study selection and data extraction. Studies reporting sex-stratified PK, PD, or safety outcomes in humans were included. Owing to methodological heterogeneity, results were synthesized narratively. Results: Twenty-seven studies met the inclusion criteria. Overall, the evidence indicates clinically meaningful sex-related differences in psychotropic drug exposure and response. Women more frequently exhibited higher dose-adjusted serum concentrations, particularly for risperidone and some SSRIs, with age-related increases more evident in females. Pharmacodynamic findings suggest that women may reach comparable dopamine D2 receptor occupancy at lower olanzapine doses. Pharmacovigilance analyses revealed sex-specific adverse event patterns, including greater reporting of endocrine-related effects and QT prolongation in women. Conclusions: Sex influences psychotropic drug exposure, pharmacodynamic sensitivity, and safety profiles in ways that may be clinically relevant. Integrating sex-aware considerations into dosing strategies could improve therapeutic precision and reduce adverse outcomes, reinforcing the importance of sex as a key variable in personalized psychiatric care. Full article

Background and objectives: Ischemic priapism is a rare but serious adverse effect of trazodone, associated with a high risk of long-term sexual dysfunction. While its urological consequences are well described, psychiatric and psychosocial outcomes remain insufficiently explored. This study assessed psychiatric and sexual sequelae following trazodone-associated ischemic priapism and compared clinical characteristics with trazodone-treated patients without priapism. Materials and Methods: In this single-center observational study, 268 adult patients receiving trazodone were analyzed, including 17 patients with ischemic priapism and 251 controls. Data on episode duration and urological management were collected. Psychiatric status and sexual functioning were evaluated through structured clinician-led interviews informed by validated psychometric frameworks during hospitalization and at 1-, 3-, and 6-month follow-up. Nonparametric analyses and Spearman rank correlations were applied. Results: Patients with priapism were significantly older than controls (44.1 ± 5.1 vs. 39.0 ± 4.4 years; p < 0.0001), while trazodone dose distribution did not differ between groups. The mean episode duration was 26.5 ± 16 h (median 24 h). Older age and longer ischemic duration were independently associated with increased treatment intensity, whereas trazodone dose was not. Persistent depressive and anxiety symptoms and impaired sexual functioning were observed in a subset of patients during follow-up. Conclusions: Trazodone-associated ischemic priapism is not only an acute urological emergency but may also lead to sustained psychiatric and sexual sequelae. Interdisciplinary follow-up should be considered to address long-term psychosocial outcomes. Full article

Background: The issue of beta blocker poisoning has received little attention, despite the widespread use of these compounds in cardiac and neuropsychiatric care. Safety profiles differ, and some beta blockers appear in poisonings far beyond what their usage rates imply. This study characterizes beta blocker intoxication patterns in Belgium, focusing on propranolol, by integrating national prescription data, poisoning reports, and adverse drug reaction records. Methods: Belgian prescription data, poison centre reports, and European ADR databases were analysed to identify intoxication patterns and demographic or clinical characteristics associated with these events. Results: Poisoning data revealed propranolol as markedly overrepresented compared to prescription rates and was the primary beta blocker implicated in self-harm-related overdoses. These cases occurred mainly in women, younger individuals, and patients with psychiatric or cardiovascular comorbidities. Co-exposures with benzodiazepines, antidepressants, and other psychoactive agents were frequent, and propranolol was linked to more complex intoxication patterns than other beta blockers. Conclusions: Propranolol shows a distinct toxicological profile and is disproportionately involved in intoxications, especially in vulnerable groups and in combination with psychoactive drugs. These findings highlight the need for greater awareness, targeted prevention, and careful monitoring. Full article

Background: Glucagon-like peptide-1 receptor agonists are increasingly prescribed for weight loss, but concerns remain regarding adverse events beyond gastrointestinal, renal, and pancreatic effects. Understanding these risks is essential to guide safe clinical application and public health policy. The study aims to characterize psychiatric risks, administration-related adverse events, and patterns of inappropriate use associated with semaglutide, liraglutide, and tirzepatide for weight management. Methods: Disproportionality analysis using proportional reporting ratios and reporting odds ratios was conducted to detect significant signals in adverse event reports within the U.S. Food and Drug Administration Adverse Event Reporting System, identifying semaglutide, liraglutide, or tirzepatide as drugs used for weight loss while excluding gastrointestinal, renal, and pancreatic adverse events. Results: Among 40,253 adverse event reports (68.6% female; median ages: semaglutide, 62 years; liraglutide, 59 years; tirzepatide, 53 years), semaglutide demonstrated the strongest disproportionality signal for psychiatric adverse events, notably anxiety (PRR 1.34, 95% CI 1.18–1.51), depression (PRR 1.83, 95% CI 1.62–2.07), and suicidal ideation (PRR 3.44, 95% CI 2.98–3.97). Tirzepatide showed markedly higher signals for injection-site reactions (PRR 7.98, 95% CI 7.8–8.18) and inappropriate use, including incorrect dosing and off-label administration (PRR 5.98, 95% CI 5.9–6.06). Conclusions: In real-world use, semaglutide is disproportionately associated with psychiatric adverse events, whereas tirzepatide demonstrates higher rates of injection-site complications and misuse. Liraglutide presents a comparatively lower risk profile. These findings underscore the need for vigilant psychiatric monitoring, patient education on injection technique and dosing, and stronger regulatory oversight to reduce misuse of GLP-1 receptor agonists for weight loss. Full article

Background/Objectives: This study aimed to investigate whether therapy with perampanel is associated with the development of psychosis or psychosis-like symptoms in patients with epilepsy. Methods: We conducted systematic electronic searches in PubMed, Google Scholar, ScienceDirect, and Scindex databases. We included articles published as case reports/case series, as well as conference abstracts and letters from the editor, if they contained enough data for analysis and quality assessment. The main inclusion criteria relate to patients who experienced psychosis or psychosis-like symptoms described by the authors during perampanel therapy or during its recent use. Results: Publications (n = 17) describing a total of 33 patients who met the inclusion criteria were included. Patient ages ranged from 11 to 70 years, and the majority of them were female (66.67%). A confirmed personal psychiatric history was identified in 60.61% of patients. The time interval between the initiation of perampanel and the onset of adverse events varied significantly across cases. The most frequently reported symptom was aggression (75.75%), followed by irritability (30.30%), while delusions or hallucinations were observed in 8 patients (24.24%). Conclusions: Clinicians should be aware that psychosis or psychosis-like symptoms may represent dose-dependent adverse effects of perampanel with a satisfactory prognosis. Identified risk factors for these developments were positive personal psychiatric history, antiseizure polytherapy at high doses, women’s gender, and focal epilepsies with secondary generalization, mainly manifested as tonic–clonic seizures. Early recognition of symptoms, followed by drug discontinuation, dose reduction, symptomatic treatment, or a combination of the mentioned strategies, is crucial for achieving better outcomes. Full article

Background/Objectives: Pharmacogenetic (PGx) testing is gaining importance in optimizing psychiatric pharmacotherapy, yet routine use remains limited due to cost and unclear patient selection criteria. The CYP Pharmacogenetic Risk Score (CYPRI) is a clinical tool designed to identify psychiatric patients most likely to benefit from PGx testing, based on medication profile, adverse drug reactions (ADRs), and therapeutic drug monitoring (TDM) results. This study aimed to evaluate the clinical relevance of the CYPRI by identifying its weaknesses and gaps in a clinical setting, propose targeted modifications to address those limitations, and assess the applicability of the improved version in a routine clinical setting. Methods: In a retrospective analysis, data from 92 patients with depression at Frankfurt University Hospital were evaluated using the CYPRI score. Its association with the clinical impact of PGx testing, measured by the IMPACT score, was analyzed using ordinal regression and Receiver Operating Characteristic (ROC) analysis. Based on the findings, a revised version of CYPRI was developed and applied to the retrospective cohorts of Frankfurt and Prague. Results: The original CYPRI score was significantly associated with increased IMPACT score, suggesting its clinical value in detecting non-normal CYP2D6 and/or CYP2C19 metabolizers. However, the corrected version (hereafter referred to as CYPRI_cor), which emphasized clinically relevant pharmacokinetic factors, showed improved clinical specificity while maintaining similar discriminative performance. In the Frankfurt cohort, the area under the curve (AUC) for CYPRI_cor was 0.68 (95% CI 0.56–0.79), and in the Prague cohort, the AUC for CYPRI_cor was 0.71 (95% CI 0.60–0.81). While the overall discriminative ability in Frankfurt was slightly lower, CYPRI_cor achieved a specificity of 0.69, enabling more precise identification of patients most likely to benefit from PGx testing. A CYPRI Cut-off of ≥4 was determined to indicate clinical impact. Conclusions: The CYPRI_cor score was designed to optimize and to rule out potential limitations of the original score, particularly regarding the attribution of ADRs and the weighting of TDM results. Although the modifications did not improve discriminative performance in the Frankfurt dataset, the proposed changes remain meaningful. Prospective clinical studies need to verify the clinical utility of the CYPRI_cor. Full article

Background/Objectives: Interpersonal violence is an increasing public health concern, and its prediction and prevention remain global challenges. This study aimed to identify prescribed medications associated with interpersonal violence in Spain. Methods: A descriptive, longitudinal and retrospective study and case-non case study of spontaneous reports of adverse drug reactions corresponding to interpersonal violence recorded in the Spanish Pharmacovigilance Database (FEDRA^®) from 1984 to 31 March 2021. Results: 533 cases were reported in the study period. The mean age was 46.70 years with ages ranging from 1 to 99 years. There were no sex differences except in child and adolescent age group where most reports were from male. Main therapeutic groups involved were nervous system (62.3%), anti-infectives for systemic use (10%) and respiratory system (8.6%). Mostly drugs reported were montelukast, levetiracetam, bupropion, donepezil, perampanel, quetiapine, fluoxetine, and lorazepam. A statistically significant association/disproportion in the notification has been found in the reporting of interpersonal violence and different drugs according to the literature, notably atomoxetine, perampanel, memantine, donepezil, montelukast and methylphenidate. Conclusions: The results highlight that interpersonal violence, while rare, could occur as a clinically relevant adverse reaction to a small subset of medications. They underscore the importance of careful prescribing, especially in vulnerable populations and in individuals with a history of psychiatric disorders. Full article

Background/Objectives: The aim of this study was to determine the suspected adverse drug reaction (ADR) profile of leukotriene receptor antagonists (LTRAs; montelukast and zafirlukast) relative to first-line asthma medications such as short-acting beta agonists (SABAs; salbutamol) and inhaled corticosteroid (ICS; beclomethasone) in the United Kingdom. to determine the chemical and pharmacological rationale for the suspected ADR signals. Methods: Properties of the asthma medications (pharmacokinetics and pharmacology) were datamined from the chemical database of bioactive molecules with drug-like properties, the European Molecular Biology Laboratory (ChEMBL). Suspected ADR profiles of the asthma medications were curated from the Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card interactive Drug Analysis Profiles (iDAP) and concatenated to the standardised prescribing levels (using Open Prescribing data) between 2018 and 2023. Results: Total ADRs per 100,000 R_x (p < 0.001) and psychiatric system organ class (SOC) ADRs (p < 0.001) reached statistical significance. Montelukast exhibited the greatest ADR rate at 15.64 per 100,000 R_x. Conclusions: Relative to the controls, montelukast displays a range of suspected system organ class level ADRs. For the credible and previously reported psychiatric ADRs, montelukast is statistically significant (p < 0.001). A mechanistic hypothesis is proposed based on polypharmacological interactions in combination with cerebrospinal fluid (CSF) levels attained. Montelukast had the highest nervous disorder ADR rate at 1.71 per 100,000 R_x, whereas beclomethasone and salbutamol had lower rates (0.43 and 0.14, respectively). These ADRs share a similar background to psychiatric ADRs with CSF penetrability involved and affecting the dopamine axis. This work further supports the monitoring of montelukast for rare but important neuropsychiatric side effects. Full article

Individuals with severe mental illness face a substantially higher risk of suicide compared with the general population, with drug overdose representing one of the most common and potentially lethal methods. This narrative review explores toxidromes frequently encountered in psychiatric populations, such as opioid, anticholinergic, and serotonergic toxicity, highlighting the clinical presentation in intentional overdose. Emphasis is placed on clinical recognition, antidote-based treatment, and systems-level strategies for the prevention of lethal overdose. We conducted a comprehensive literature search of PubMed, Google Scholar, and Web of Science for English-language articles using combinations of the following keywords: mental disorders; persons with psychiatric disorders; drug overdose; poisoning; serotonin syndrome; neuroleptic malignant syndrome; anticholinergic agents/poisoning; cholinergic antagonists/poisoning; psychotropic drugs/adverse effects; substance-related disorders; drug-related side effects and adverse reactions; polypharmacy; suicide, attempted; emergency service, hospital. By embedding toxidrome awareness into routine emergency and psychiatric practice, we aim to expedite treatment and improve patient outcomes. Full article

Background/Objectives: Mental health awareness is rising; thus, neurological and psychiatric side effects also benefit from increased attention from the medical and scientific community. Ibuprofen is a well-known non-steroidal anti-inflammatory drug (NSAID) that is often available over-the counter (OTC) for both adults and children, expressing good efficacy in reducing pain and fever through non-selective cyclooxygenase inhibition. As ibuprofen has already been associated with different neuropsychiatric disorders, the aim of this study was to perform an up-to-date analysis of such signals detected in the cases reported in EudraVigilance (EV). Methods: The disproportionality analysis offered a contextual insight into the real-world situation depicted in the analyzed database. Results: From the total cases reported for ibuprofen (n = 58,911), 13.9% contained nervous system disorders (n = 8214) and 10.7% entailed psychiatric disorders (n = 6295). The cases were distributed between all age groups, with a sensible higher incidence in teenagers and in women in general. Severe cases, including deaths, have been reported. By comparison with ketoprofen, acetylsalicylic acid, and diclofenac, ibuprofen presented a higher probability of reporting psychiatric and behavioral symptoms. Regarding cognitive and attention disorders and disturbances, no disproportionate signal was observed between ibuprofen and all other NSAIDs. Sleep disturbances (hypersomnia, narcolepsy and sleep paralysis) are reported as more probable for ibuprofen than for acetylsalicylic acid, naproxen, and diclofenac. A higher risk of reporting suicidal and self-injurious behaviors was noted for ibuprofen versus all other selected NSAIDs. A limitation of the study can be noted as due to suspected causality, not an established one, and EV reports cannot accurately determine adverse drug reaction frequencies. Conclusions: Considering that ibuprofen is easily accessible as an OTC drug and the higher probability of reporting several neuropsychiatric adverse effects as shown by this study, patient counseling, when possible, and general education for the public are valuable tools in managing these adverse reactions. Full article