Search Results (31)

People with cystic fibrosis may experience polypharmacy, which can increase the risk of drug induced complications such as adverse events and drug–drug interactions. This study aimed to examine the prevalence of adverse events and to identify potential drug–drug interactions associated with elexacaftor/tezacaftor/ivacaftor (ETI). Three databases, the Australian Therapeutic Goods Administration Database of Adverse Event Notification (TGA DAEN), the Canada Vigilance Adverse Reaction Online Database (CVAROD), and the USA Food and Drug Administration Adverse Event Reporting System (FAERS) Database were searched for spontaneous ETI adverse events between 2019 and 2024. Descriptive analysis of the data was undertaken. The FAERS database was analysed to identify adverse events of interest such as anxiety and depression and concomitant drugs prescribed with ETI. A total of 10,628 ETI associated adverse events were identified in all system organ classes. The incidence of psychiatric adverse events ranged from 7 to 15% across the three databases. Potential drug–drug interactions with CYP 3A4/5 strong inhibitors and strong inducers were identified from the FAERS database and azole antifungals were implicated in several ETI dose modifications. The prevalence and types of ETI adverse events were varied and use of concomitant drugs with potential drug interactions was significant, requiring more research to manage them. Full article

Background: Mental health issues among medical students have gained increasing attention globally, with studies indicating a high prevalence of psychological disorders within this population. The use of antidepressants and anti-anxiety medications has become a common response to these mental health challenges. However, it is crucial to understand the extent of their usage and associated effects on students’ mental health and academic performance. This cross-sectional study explored the use of antidepressants and anti-anxiety drugs and their impact on the mental health of medical students in Saudi Arabia. Methods: A cross-sectional survey of 561 medical students from 34 universities was conducted between March and July 2024. An anonymous online questionnaire was used to collect sociodemographic, mental health, and medication usage-related information. Results: Most of the participants were female (71.5%) and aged 21–25 years (62.7%). Approximately 23.8% of them used antidepressants, 5.6% reported using anti-anxiety medications, and 14.0% used both types of medication. Among the medication users, 71.7% were using selective serotonin reuptake inhibitors (SSRIs), and 28.3% were using other medications. Adverse drug reactions were reported by 58.8% of the participants, and 39.6% changed drugs with inadequate efficacy. Notably, 49.0% of the respondents who have ever used medications discontinued their medication without consulting a healthcare professional. Despite these challenges, 62.0% of the participants felt that their medications had a positive impact on their academic performance, 73.4% believed that the benefits outweighed the drawbacks, and 76.2% expressed a willingness to continue taking their medication. In particular, 77.6% agreed that treatment with these drugs could prevent mental breakdowns. Sleep duration, physical activity, and family history of psychiatric disorders were significantly associated with medication use, with p values of 0.002, 0.014, and 0.042, respectively. Conclusions: These results shed light on the need to understand the prescribing practices of antidepressant and anti-anxiety drugs among medical students while promoting the appropriate use of these medications among the students. There is a need to incorporate mental health interventions into counseling services and awareness programs to support students. Future longitudinal studies are needed to explore long-term trends. Full article

Background/Objectives: During the COVID-19 pandemic, several antivirals were approved or repurposed, but their safety profiles have not been fully compared. Pharmacovigilance data help clarify how these drugs perform in real-world use. Methods: This study performed a comparative pharmacovigilance analysis of eight antivirals used or tested during the COVID-19 pandemic, based on individual case safety reports (ICSRs) retrieved from the EudraVigilance database, reported up to 9 February 2025 and extracted from the official platform on 12 February 2025. Adverse reactions were assessed by system organ class (SOC), demographic patterns, and seriousness, and disproportionality analysis (reporting odds ratio (ROR)) was conducted to identify potential safety signals. Results: A total of 64,776 ICSRs were analyzed. Among approved antivirals, nirmatrelvir/ritonavir (NTV/r) accounted for 13.4% (n = 8693) of reports, while remdesivir (RDV) represented 6.3% (n = 4105). Repurposed antivirals such as ribavirin and lopinavir/ritonavir dominated the dataset, together making up over 80% (n = 51,978) of all reports. RDV was associated with a high proportion of serious adverse events (84%, n = 3448), and showed consistent ROR signals in hepatobiliary, renal, cardiac, and general disorders, with values exceeding 2 in several comparisons. NTV/r displayed a milder overall profile, but with positive RORs for psychiatric disorders, gastrointestinal disorders, and product-related issues. The most affected SOCs across all drugs included general disorders (31.6%, n = 20,493), gastrointestinal (19.5%, n = 12,625), nervous system (17.8%, n = 11,511), and investigations (20.4%, n = 13,219). Demographic analysis showed that most events occurred in adults aged 18–64, with RDV more often reported in elderly patients and NTV/r more frequently associated with reports from female patients and non-healthcare reporters. Conclusions: This study highlights distinct pharmacovigilance profiles of COVID-19 antivirals and supports the role of real-world data in guiding safer therapeutic choices. Full article

Aim/Objectives: To investigate whether frailty predicts adherence to psychotropic drug treatment or adverse drug reactions, within 6 months after treatment initiation. Methods: A prospective cohort study including 77 patients over the age of 65, treated in one large psychiatric institute in the Netherlands. Patients were assessed at baseline for their frailty status, using different operationalizations of the Fried frailty criteria. Data on duration of psychotropic drug treatment and number of reported adverse drug reactions were retrieved from electronic patient files. Regression analyses were adjusted for age, sex, patient setting, and polypharmacy as potential confounders. Results: Frail patients were not significantly more likely to discontinue psychotropic treatment than non-frail patients (OR = 1.4; 95% CI 0.6–3.7, p = 0.468). Time to treatment discontinuation was also not statistically different between both study groups (HR = 0.8; 95% CI 0.4–1.6, p = 0.498), and neither was the number of adverse drug reactions (OR = 1.6, 95% CI 0.6–4.1, p = 0.345). Conclusions: We could not demonstrate a statistically significant effect of frailty as predictor of discontinuing psychotropic treatment or adverse drug reactions, but a lack of power may also explain our results. A more comprehensive frailty assessment may be needed to predict treatment adherence or adverse drug reactions in psychiatric patients. Full article

Antiseizure medication (ASM) induced metabolic syndrome (AIMetS) is a common adverse drug reaction (ADR) of pharmacotherapy for epilepsy and psychiatric disorders. However, the sensitivity and specificity of blood biomarkers may be insufficient due to the influence of combined pathology, concomitant diseases, and the peculiarities of the metabolism of ASMs in patients with epilepsy. Methods: The presented results of experimental and clinical studies of microRNAs (miRs) as epigenetic biomarkers of MetS and AIMetS, which were entered into the different databases, were analyzed for the last decade (2014–2024). Results: A systematic review demonstrated that miRs can act as promising epigenetic biomarkers of key AIMetS domains. However, the results of the review demonstrated the variable role of various miRs and their paralogs in the pathogenesis of AIMetS. Therefore, as part of this study, an miRs signature was proposed that allows us to assess the risk of developing and the severity of AIMetS as low risk, medium risk, and high risk. Conclusions: The mechanisms of development and biomarkers of AIMetS are an actual problem of epileptology, which is still far from being resolved. The development of panels (signatures) of epigenetic biomarkers of this widespread ADR may help to increase the safety of pharmacotherapy of epilepsy. However, to increase the sensitivity and specificity of circulating miRs in the blood as biomarkers of AIMetS, it is necessary to conduct “bridge” studies in order to replicate the results of preclinical and clinical studies into real clinical practice. Full article

Remdesivir (RDV) and nirmatrelvir/ritonavir (NMVr) are among the most widely used antivirals in the treatment of COVID-19, aiming to reduce disease severity and progression. Adverse neuropsychiatric effects, such as anxiety, sleep disturbances, and movement disorders, have emerged as significant concerns associated with these treatments. To better understand the safety profiles of RDV and NMVr, this study performs a pharmacovigilance analysis of individual case safety reports (ICSRs) from the EudraVigilance (EV) database. Objectives: This study evaluates the risk of neuropsychiatric adverse events associated with RDV and NMVr. Comparisons with other antiviral drugs, including darunavir, sofosbuvir, ribavirin, tenofovir, ritonavir, and sotrovimab, are also performed to develop a comprehensive understanding of the safety profiles. Methods: A retrospective analysis of ICSRs submitted to EV until 7 July 2024, with data extraction on 12 July 2024, was conducted. Demographic characteristics (age, sex, geographic region, and reporter type) and case severity were included in the descriptive analysis. Disproportionality analysis using reporting odds ratio (ROR) and 95% confidence intervals (CI) was performed to compare adverse drug reaction (ADRs) frequencies across 27 system organ classes (SOCs), with emphasis on “Nervous system disorders” and “Psychiatric disorders. Results: The total number of ICSRs was significantly higher for NMVr (n = 8078) compared to RDV (n = 3934). Nervous system disorders accounted for 3.07% of the total RDV reports and for 17.31% of NMVr reports, while psychiatric disorders represented 0.92% of the total ADRs reported for RDV (n = 60) and 3.61% for NMVr (n = 672). On the other hand, RDV showed a significantly lower frequency of reporting headache compared to NMVr (ROR: 0.1057; 95% CI: 0.0676–0.1653). Conclusions: NMVr presents a higher risk of neuropsychiatric ADRs than RDV, underscoring the need for enhanced monitoring, particularly in patients with preexisting central nervous system (CNS) conditions. These findings contribute to optimizing antiviral safety and informing clinical decision making. Full article

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

Background/Objectives: Schizophrenia is a chronic psychiatric disorder usually managed with antipsychotics, which can cause adverse drug reactions (ADRs) that may impact patients’ attitudes toward their treatment, as well as treatment adherence. This study aimed to assess the influence of ADRs and other factors on treatment attitudes among female patients with schizophrenia. Methods: A cross-sectional study was conducted at the Vrapče Psychiatry Clinic with 109 female schizophrenia patients. The DAI-10 (Drug Attitude Inventory) questionnaire was used to assess attitudes toward treatment. Data on their demographic details, pharmacotherapy, ADR occurrence and ADR reporting rates were collected. Multiple regression analyses were used to identify predictors of DAI-10 scores. Results: Patients using more medications and those experiencing ADRs had lower DAI-10 scores, indicating less favorable attitudes (F (2, 106) = 7.364, p = 0.001, R² = 0.105). ADRs, primarily extrapyramidal symptoms and weight gain, were reported by 43.1% of patients; however, only one patient formally reported them. First-generation antipsychotics were associated with a higher prevalence of ADRs (χ² = 4.969, df = 1, p = 0.022). Conclusion: Negative experiences with ADRs significantly impact patients’ attitudes and adherence. Low ADR reporting rates highlight the need for better pharmacovigilance education. Enhancing patient awareness may foster more positive attitudes and adherence, potentially improving patient outcomes. 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

Background/Objectives/Methods: Atopic dermatitis (AD) impacts various aspects of patients’ lives including personal life, psychological aspects/disturbances (e.g., depression, anxiety, or even suicidal thoughts), school, and work-related activities, including career advancement. The aim of this narrative review is to present the latest information available on how to best approach AD patient management, as well as decisions regarding standard/advanced systemic therapy, by gathering evidence from the relevant medical literature (PubMed and other prominent medical databases). Results: Thus, AD patient management and decisions regarding advanced/systemic therapy are complex, requiring the consideration of multiple disease-related factors: age; disease severity; patient medical history and comorbidities; previous topical therapy use and any adverse reactions; treatment efficacy concerns; patient preferences, expectations and fears; pregnancy planning; ability and willingness to adhere to the treatment regimen; impact on related risks; and any associated psychological or psychiatric issues. Current guidelines and systematic reviews support the safety and efficacy of systemic therapy including conventional drugs (cyclosporine, methotrexate, and azathioprine), biologics (dupilumab and tralokinumab), and JAK inhibitors (baricitinib, upadacitinib, and abrocitinib) recommended for treating moderate and severe AD. Recently, additional biologics have been evaluated in clinical trials, including lebrikizumab, nemolizumab, eblasakimab, and OX40/OX40L, among others. Conclusions: The most recently suggested approach to treating AD patients suggests focusing on therapy that targets and achieves minimal disease activity (MDA), where therapy decisions are informed by both the patient and the clinician. Available data also indicate the importance of a personalized, stepwise, and multidisciplinary approach. This type of approach promotes patient compliance, satisfaction with therapy, and increased engagement, which all lead to better patient outcomes. Full article

Background: QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens. Secondly, we test the predictive value of well-known risk factors for QT prolongation. Results: The median patient age was 49 years (IQR 34–64) for patients treated with a median of nine drugs (IQR 6–12) and a median QT-prolonging drug sum of three daily defined dosages (IQR 1.88–4.76). We extracted 290 ECGs for patients where pharmacist-led-medication reviews (PMRs) identified an increased risk of QT prolongation and 190 ECGs for patients with no such risk, identifying 33 cases of verified QT prolongation equally distributed between groups. Unadjusted regression analysis revealed that advanced age (OR 3.27 CI 95% 1.60–6.84) and cardiovascular comorbidity (OR 3.53 CI 95% 1.71–7.29) were associated with manifest QT prolongation, while the QT-prolonging drug load was not. Methods: We reviewed electronic health records (EHRs) of 799 psychiatric inpatients exposed to PMRs made from 1 September 2016 to 31 December 2018 in Region Zealand Denmark. Conclusions: Patients at risk of QT prolongation as identified by drug reviews rarely manifests with actual QT prolongation. Non-pharmacological risk factors seem to be better predictors for identifying patients with QT prolongation. Full article

Metabolic syndrome (MetS) is the most common adverse drug reaction from psychiatric pharmacotherapy. Neuroreceptor blockade by the antipsychotic drug clozapine induces MetS in about 30% of patients. Similar to insulin resistance, clozapine impedes Akt kinase activation, leading to intracellular glucose and glutathione depletion. Additional cystine shortage triggers tryptophan degradation to kynurenine, which is a well-known AhR ligand. Ligand-bound AhR downregulates the intracellular iron pool, thereby increasing the risk of mitochondrial dysfunction. Scavenging iron stabilizes the transcription factor HIF-1, which shifts the metabolism toward transient glycolysis. Furthermore, the AhR inhibits AMPK activation, leading to obesity and liver steatosis. Increasing glucose uptake by AMPK activation prevents dyslipidemia and liver damage and, therefore, reduces the risk of MetS. In line with the in vitro results, feeding experiments with rats revealed a disturbed glucose-/lipid-/iron-metabolism from clozapine treatment with hyperglycemia and hepatic iron deposits in female rats and steatosis and anemia in male animals. Decreased energy expenditure from clozapine treatment seems to be the cause of the fast weight gain in the first weeks of treatment. In patients, this weight gain due to neuroleptic treatment correlates with an improvement in psychotic syndromes and can even be used to anticipate the therapeutic effect of the treatment. Full article

As the most common psychiatric symptom, depression represents a subject of high interest for the medical community. Background/Objectives: International guidelines consider selective serotonin reuptake inhibitors (SSRIs) the first-line treatment of depression. Although having better efficacy and tolerability in comparison to tricyclic antidepressants or monoamine oxidase inhibitors, the diversity and potential severity of adverse effects and interactions manifested by SSRIs, combined with the frequency of prescriptions, lead to the necessity of evaluating real-world data. The aim of this study was to identify and evaluate the drug interactions reported in EudraVigilance (EV) for the six SSRIs representatives that are authorized in Europe: fluoxetine (FXT), fluvoxamine (FVM), citalopram (CIT), escitalopram (ESC), paroxetine (PAR) and sertraline (SER). The entire class of SSRIs was examined as a comparator to identify whether one of the representatives was more prone to reporting. Methods: Descriptive analysis and disproportionality analysis were conducted on data extracted from the EV database. Results: A total of 326,450 adverse reactions (ADRs) were reported for the SSRIs group. Approximately a quarter of these (n = 83,201; 25.46%) were reported for SER and 22.37% (n = 73,131) for PAR. Of the total ADRs reported, 2.12% (n = 6925) represent preferred terms related to drug-drug interactions (DDIs): SER (n = 1474; 22.37%), CIT (n = 1272, 19.86), and FXT (n = 1309, 19.83%). Specific ADRs related to inhibitory activity represent 0.98%, and for potentiating activity, 1.89%. Conclusions: Although representing a small value of the total ADRs, DDIs may be related to severe outcomes. Awareness should be raised for this category of ADRs that can be reduced by the joined efforts of physicians and pharmacists. Full article

(1) Background: The utilization of high-quality evidence regarding the safety of anti-seizure medications (ASMs) is constrained by the absence of standardized reporting. This study aims to examine the safety profile of ASMs using real-world data. (2) Methods: The data were collected from the Korea Adverse Event Reporting System Database (KAERS-DB) between 2012 and 2021. In total, 46,963 adverse drug reaction (ADR)–drug pairs were analyzed. (3) Results: At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). For non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). Non-SCBs were associated with dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Rash, pruritus, and urticaria occurred, on average, two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher’s exact test, p < 0.0001). (4) Conclusions: Based on real-world data, the safety profiles of ASMs were identified. The ADRs induced by SCBs exhibited different patterns when compared to those induced by non-SCBs. Full article

In recent years, a series of recommendations have been issued regarding the administration of drugs because of awareness of the serious side effects associated with certain classes of drugs, especially in vulnerable patients. Taking into account the obligation of the continuous improvement of professionals in the medical fields and the fact that we are in the midst of a “malpractice accusations pandemic”, through this work, we propose to carry out a “radiography” of the scientific literature regarding adverse effects that may occur as a result of the interaction of drugs with the physiopathological particularities of patients. The literature reports various cases regarding different classes of drugs administration associated with adverse effects in the elderly people, such as fluoroquinolones, which can cause torsade de pointes or tendinopathy, or diuretics, which can cause hypokalemia followed by torsade de pointes and cardiorespiratory arrest. Also, children are more prone to the development of adverse reactions due to their physiological particularities, while for pregnant women, some drugs can interfere with the normal development of the fetus, and for psychiatric patients, the use of neuroleptics can cause agranulocytosis. Considering the physiopathological particularities of each patient, the drug doses must be adjusted or even completely removed from the treatment scheme, thus requiring the mandatory active participation both of clinician pharmacists and specialists in the activity of medical-pharmaceutical analysis laboratories within the structure of hospitals. Full article