Intentional Overdose Research Articles

Tapentadol: navigating the complexities of abuse, patient safety & regulatory measures

Aim To evaluate tapentadol abuse cases by analyzing real-world data and identifying under-reporting countries from Southeast Asian Region (SEAR) to enhance vigilance. Method A retrospective, observational study from 2013 to March 2024 using VigiBase was conducted. Result Tapentadol-related abuse falls within the System Organ Class (SOC) categories of psychiatric disorder, nervous system disorder and injury, poisoning, and procedural complications. These are further categorized into Preferred Terms (PT) such as anxiety, delirium, Central Nervous System toxicity, depressive disorder, drug abuse, dependence/withdrawal syndrome, and overdose using the Medical Dictionary for Regulatory Activities (MedDRA) system. Among the 11 countries in the SEAR, India is the only country to report cases of tapentadol-related abuse, no Individual Case Safety Reports (ICSRs) related to tapentadol abuse have been submitted from other SEAR nations. Out of 127 ICSRs concerning tapentadol-related adverse events reported in India, 20 cases involved abuse. Focusing on the ICSRs submitted in India, the reported adverse reactions included anger(n = 1,10%), anxiety (n = 2, 10%), delirium (n = 1, 5%), drug abuse (n = 4, 20%), drug dependence/withdrawal syndrome (n = 7, 35%), intentional overdose (n = 2, 10%), depressive disorder (n = 1, 5%), euphoric mood (n = 1, 5%), and product misuse (n = 1, 5%) indicating a concerning pattern of substance abuse. Conclusion Stringent regulatory actions are needed to curb this practice in India, such as rescheduling tapentadol from Schedule H (Prescription drugs) to Schedule X(Narcotic drugs) in India could offer more regulatory oversight and measures to reduce risks related to abuse, addiction, and dependence while enhancing patient safety in pain management practices. Additionally, tapentadol should be closely monitored in other SEAR countries due to its potential for dependence. This study also emphasizes the importance of encouraging SEAR countries to report more Adverse Drug Reactions (ADRs), which would facilitate the implementation of more rigorous regulatory measures.

Baclofen-related deaths in Australia 2000–2022

In Australia, the therapeutic indication of baclofen (oral tablets) is for the treatment of muscle spasm. Deaths related to baclofen have been reported, as well as misuse, dependence and self-poisoning. This national retrospective study aimed to investigate the number, characteristics, circumstances, and toxicology of baclofen-related deaths in Australia, 2000–2022. We identified 102 baclofen-related deaths, with a mean age of 45.6 years and 51 % being male. Circumstances of death were: intentional toxicity (54.9 %), unintentional toxicity (30.4 %), unintentional toxicity/disease (9.8 %), and accidental injury (4.9 %). Multiple sclerosis or spinal injury was documented in 15.7 % of cases, substance use problems in 43.1 % and specifically alcohol use problems in 38.2 %. Mental health problems were documented in 73.5 %, a previous self-harm or suicide attempt in 30.4 %, and chronic pain in 37.3 %. The median baclofen blood concentration for all cases was 3.10 mg/L (25th 0.70, 75th 8.10, range 0.04–110.00), unintentional toxicity 1.95 mg/L (25th 0.70, 75th 4.35, range 0.04–24.0), intentional toxicity 6.00 mg/L (25th 1.10, 75th 13.0, range 0.05–110.0). Concomitant substance use was seen in 93.8 %, with antidepressants (69.8 %) and benzodiazepines (64.6 %) most frequently detected. In conclusion, the ‘typical’ case was middle-aged, most dying due to intentional toxicity, and likely to have a history of mental health and substance use problems. We suggest caution is needed in prescribing baclofen given its potential to be used in intentional and non-intentional overdose.

Exploring Human Misuse and Abuse of Veterinary Drugs: A Descriptive Pharmacovigilance Analysis Utilising the Food and Drug Administration’s Adverse Events Reporting System (FAERS)

Introduction: Evidence suggests an increasing misuse of veterinary medicines by humans. This study aims to analyse Adverse Events (AEs) associated with selected veterinary products using the Food and Drug Administration Adverse Events Reporting System (FAERS). Methods: A descriptive pharmacovigilance analysis was conducted on AEs related to 21 drugs approved for human and/or animal use. Results: A total of 38,756 AEs, including 9566 fatalities, were identified. The United States reported the highest number of cases (13,532), followed by Canada (2869) and the United Kingdom (1400). Among the eight drugs licenced exclusively for animals, levamisole, pentobarbital, and xylazine were most frequently reported. Reports predominantly involved males (57%) from the 18–64 age group, with incidents related mainly to overdose, dependence, and multi-agent toxicities. Unmasking techniques revealed ‘intentional overdose’ as the primary reaction. Polysubstance use was evident in 90% of the drugs, with benzodiazepines/Z-drugs and opioids as common co-used classes. Conclusions: Veterinary medications are increasingly infiltrating the illicit drug market due to their pharmacological properties. This trend highlights the need for heightened vigilance and awareness to prevent further public health risks associated with the adulteration of illicit substances with veterinary products like xylazine and pentobarbital.

Atrial fibrillation with Slow Ventricular response as a sign of Digoxin toxicity Secondary to Acute Renal failure.

Digoxin is a cardiac glycoside that has been used for centuries for atrial fibrillation (AFib) and congestive heart failure (CHF). Digoxin has a narrow therapeutic index with a potential for toxicity that can be life-threatening1-5. Toxicity can result from accidental or intentional overdose, renal failure, and/or hypokalemia. Cardiac manifestations of digoxin toxicity cause dysrhythmias of different types2,6. Bidirectional ventricular tachycardia is a specific dysrhythmia in the setting of digitalis toxicity, but AFib with slow ventricular response (SVR) is another digoxin toxicity-related dysrhythmia7. Here, we report AFib with SVR as a sign of digoxin toxicity secondary to acute renal failure (ARF).

Take-home naloxone in multicentre emergency settings: the TIME feasibility cluster RCT.

Opioids kill more people than any other drug. Naloxone is an opioid antagonist which can be distributed in take-home 'kits' for peer administration (take-home naloxone). To determine the feasibility of carrying out a definitive randomised controlled trial of take-home naloxone in emergency settings. We used Welsh routine data (2015-21) to test the feasibility of developing a discriminant function to identify people at high risk of fatal opioid overdose. We carried out a cluster randomised controlled trial and qualitative study to examine experiences of service users and providers. We assessed feasibility of intervention and trial methods against predetermined progression criteria related to: site sign-up, staff trained, identification of eligible patients, proportion given kits, identification of people who died of opioid poisoning, data linkage and retrieval of outcomes. This study was carried out in the emergency environment; sites comprised an emergency department and associated ambulance service catchment area. At intervention sites, we invited emergency department clinicians and paramedics to participate. We recruited adult patients who arrived at the emergency department or were attended to by ambulance paramedics for a problem related to opioid use with capacity to consent to receiving the take-home naloxone and related training. Usual care comprised basic life support plus naloxone by paramedics or emergency department staff. The take-home naloxone intervention was offered in addition to usual care, with guidance for recipients on basic life support, the importance of calling the emergency services, duration of effect, safety and legality of naloxone administration. With low numbers of opioid-related deaths (1105/3,227,396) and a high proportion having no contact with health services in the year before death, the predictive link between death and opioid-related healthcare events was weak. Logistic regression models indicated we would need to monitor one-third of the population to capture 75% of the decedents from opioid overdose in 1-year follow-up. Four sites participated in the trial and 299 of 687 (44%) eligible clinical staff were trained. Sixty take-home naloxone kits were supplied to patients during 1-year recruitment. Eligible patients were not offered take-home naloxone kits 164 times: 'forgot' (n = 136); 'too busy' (n = 15); suspected intentional overdose (n = 3). Service users had high levels of knowledge about take-home naloxone. They were supportive of the intervention but noted concerns about opioid withdrawal and resistance to attending hospital for an overdose. Service providers were positive about the intervention but reported barriers including difficulty with consenting and training high-risk opioid users. We were able to calculate costs to train staff at three sites (£40 per AS and £17 in Site 1 ED). No adverse events were reported. Progression criteria were not met - fewer than 50% of eligible staff were trained, fewer than 50% of eligible patients received the intervention and outcomes were not retrieved within reasonable timescales. The take-home naloxone intervention needs to be developed and evaluated in emergency care settings, with appropriate methods. The Take-home naloxone Intervention Multicentre Emergency setting study was interrupted by coronavirus disease. This study did not meet progression criteria for intervention or trial methods feasibility, so outcomes were not followed up and a fully powered trial is not planned. This trial is registered as ISRCTN13232859. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/91/04) and is published in full in Health Technology Assessment; Vol. 28, No. 74. See the NIHR Funding and Awards website for further award information.

Intentional Overdose in a Young Male Patient: Limitations of Current Mental Health Models at the Initial Point of Care for High-Risk Patient Cohorts

Intentional Overdose in a Young Male Patient: Limitations of Current Mental Health Models at the Initial Point of Care for High-Risk Patient Cohorts

An intentional overdose of ultra-long-acting insulin analogue complicated by treatment refusal in a patient with mixed personality disorder and type 2 diabetes mellitus

An intentional overdose of ultra-long-acting insulin analogue complicated by treatment refusal in a patient with mixed personality disorder and type 2 diabetes mellitus

Trends in Nonfatal Overdose Rates Due to Alcohol and Prescription and Illegal Substances in Colombia, 2010-2021.

Objectives. To examine drug overdoses in Colombia by type of substance, sex, age, and intent using data from a health surveillance system from 2010 to 2021. Methods. We characterized data by year, type of substance, and sociodemographic variables. We calculated age-adjusted overdose rates by substance type, sex, age groups, and intent. We used Poisson regression models to examine trend differences across sex and age groups. Results. Age-adjusted rates of drug overdoses increased from 8.51 to 40.52 per 100 000 during 2010 to 2021. Men, compared with women, had higher overdose rates for every substance, except for opioids and psychotropics. Drug overdose rates involving cannabis and stimulants increased steadily until 2017 but decreased afterward. Overdose rates involving psychotropic medication increased greatly during 2018 to 2021, mainly because of intentional overdoses in young women. Conclusions. Overdoses involving illegal drugs decreased in recent years in Colombia; however, the continuous increase in intentional psychotropic overdose rates highlights the need for prevention efforts to curb this trend. Health surveillance systems are an important tool that can guide overdose prevention efforts in countries with limited data resources. (Am J Public Health. Published online ahead of print September 12, 2024:e1-e9. https://doi.org/10.2105/AJPH.2024.307786).

Clozapine may consistently protect from suicidal behaviors while other antipsychotics may lack a specific protective effect: a comprehensive VigiBase study interpreted in the context of the prior literature

ABSTRACT Background In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine’s anti-suicidal effect, but the forensic literature stresses its lethality during overdoses. Research design and methods Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis. Results The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC025 = 0.454 to IC975 = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC025 = 1.323 to IC975 = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC025 = 0.864 to IC975 = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC025 = 1.026 to IC975 = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia. Conclusion This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.

Take-home naloxone administered in emergency settings: feasibility of intervention implementation in a cluster randomized trial

BackgroundOpioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT).MethodsWe undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019–2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events.ResultsAt two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported.ConclusionStaff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned.Trial RegistrationISRCTN13232859 (Registered 16/02/2018).

Insulin-Related Suicides-3 Cases.

Insulin is a pancreas-produced hormone, which is essential for normal life. In persons with diabetes, who lack sufficient production of endogenous insulin, the availability of exogenously-produced and administered insulin represents an extremely valuable, life-preserving medical advancement. Unfortunately, as with many other medications, overdosage with insulin can and does occur, sometimes in an intentional suicidal manner. Another possible insulin-related suicidal action involves the intentional cessation of insulin therapy by someone who relies on insulin for survival. In this case series, we present 3 cases of insulin-related suicides, including two related to intentional insulin overdose and one where a known diabetic purposefully stopped taking insulin in order to commit suicide.

Intentional Insulin Overdose and Depression in Subjects with and Without Diabetes Mellitus: A Commentary.

Insulin is an essential medication for people with type 1 diabetes mellitus and for some people with type 2 diabetes. Interestingly, insulin abuse has been reported as a mode of suicide, not only among people with diabetes, but also among their relatives, and among medical and paramedical personnel who have access to insulin. The aim of the present commentary was to raise awareness of potential depression-related intentional insulin overdose and its complications, as well as of the diagnosis and treatment of this entity. Insulin overdose may lead to severe and prolonged hypoglycemia, hypoglycemic coma, and death. Moreover, hypokalemia, hypomagnesemia, hypophosphatemia, and elevated liver enzymes are common. Insulin overdose should be suspected among people with diabetes in case of unexplained prolonged hypoglycemia and among people without diabetes who exhibit hypoglycemia and may have access to diabetic medications. The ratio of insulin to C-peptide helps distinguish exogenous insulin administration from endogenous secretion. The cornerstone of therapy is prompt administration of concentrated glucose infusions for days with simultaneous oral intake, when possible, and intense glucose monitoring to prevent hypoglycemia. Moreover, monitoring of serum electrolyte levels is recommended. Finally, psychiatric evaluation aiming at early identification of depression and suicidality is of paramount importance.

Clinical safety of daridorexant in insomnia treatment: Analysis of FDA adverse event reports

ObjectiveDaridorexant, a novel dual orexin receptor antagonist, was approved by the FDA in 2022 for the treatment of insomnia in adults. The aim of this study is to delve into the adverse events (AEs) of daridorexant by analyzing data from the FAERS database, to assess its safety and effectiveness in clinical applications. MethodsThis study selected data from the FAERS database from the first quarter of 2022 to the third quarter of 2023. Various data analysis methods were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), to assess AEs related to daridorexant. ResultsThe study analyzed a total of 2,624,030 AE reports, of which 1318 were related to daridorexant. It identified 59 preferred terms (PTs) involving 23 system organ classes (SOCs). Signal mining identified new potential AEs related to daridorexant, including sleep-related psychiatric symptoms (nightmare, abnormal dreams, sleep terror, etc.), emotional and perceptual abnormalities (hallucination, depression, agitation), physiological and behavioral responses (palpitations, dry mouth, energy increased, etc.), suicide risk (suicidal ideation, intentional overdose), and other special concern AEs (tachyphrenia, sleep-related eating disorder, hypersensitivity). ConclusionAlthough some new potential AEs have been identified, these findings need further verification in broader datasets and long-term studies due to limitations in data sources and analysis methods. Future research should comprehensively assess the safety and effectiveness of daridorexant, providing more accurate guidance for medical professionals in the treatment of insomnia.

Toxicologic analysis of 35 drugs in post mortem human blood samples with focus on antihypertensive and antiarrhythmic drugs

Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS).Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.

Implementation and evaluation of interprofessional overdose review team recommendations following intentional or accidental overdose events.

Drug overdose death rates in the United States remain high despite efforts to mitigate this risk. Many communities and hospitals across the country have implemented overdose review teams, including local overdose fatality review teams or postoverdose intervention programs, to address the opioid crisis. The goal of most of these teams is to identify missed opportunities or patient-specific interventions to prevent future opioid overdose fatalities. Few overdose review teams review a combination of both fatal and nonfatal overdose events. The Veterans Affairs Tennessee Valley Healthcare System implemented a novel overdose review team (ORT) that collaboratively reviews all overdose incidents regardless of fatality, intent, or substance involved. This practice description characterizes reported facility overdose events and patient-specific risk-mitigation strategies recommended by the ORT, highlights the implementation rate and time to implementation of ORT recommendations, and discusses potential areas for process improvement. This practice highlights the potential impact of a pharmacist-led, interdisciplinary ORT following accidental or intentional overdose events involving any substance or medication. Key patient-specific interventions implemented following ORT recommendations included overdose prevention education and naloxone distribution, prescribing of medications for opioid use disorder and/or alcohol use disorder, reducing medication supply to limit lethal means access, and facilitation of mental health and/or substance use disorder specialty appointments. Further research to evaluate clinical outcomes related to specific ORT interventions should be considered.

A Case Report of Delayed Opioid Toxidrome After Administration of Naloxone.

Opioid use is an epidemic that plagues the United States. Patients frequently present to the emergency department (ED) after opioid toxicity, which can lead to respiratory failure, apnea, and death. Although there is an effective antidote, naloxone, the current guidelines surrounding post-naloxone administration monitoring are loosely defined. We present a case in which an individual was administered naloxone after an intentional opioid overdose and was monitored for four hours, as is standard in our institution. He remained in the ED for additional workup following this observation period and subsequently experienced signs of severe respiratory depression, requiring bag-valve-mask ventilation, naloxone, and admission. Had he been discharged, as is typical after a four-hour observation period, the consequences could have been fatal. We present multiple theories as to why his opioid toxidrome may have presented in a delayed manner, including ingestion of fentanyl analogues and variability in metabolization of both opioids and naloxone. We also explore alternative overdose antidote products approved by the US Food and Drug Administration, which may impact post overdose care. This case suggests that the correct amount of time to monitor patients after naloxone administration may be longer than originally thought. Our aim in this article was to further the discussion regarding the most appropriate observation period in cases of opioid toxicity.

No change in substance use disorders or overdose after implementation of state Earned Income Tax Credit (EITC)

BackgroundInadequate income is associated with higher likelihood of experiencing a substance use disorder (SUD). This study tests whether the earned income tax credit (EITC), which issues supplemental income for workers with children in the U.S., is associated with lower rates of SUD and fatal overdose. MethodsWe examined the effects of state-level refundable EITC presence and generosity (i.e., state EITC rate as a % of federal rate) on SUD-related outcomes (SUD prevalence and intentional and unintentional fatal overdose) using a difference-in-difference methodology, with both two-way fixed-effects models and event study plots. Several sensitivity analyses were conducted to assess the robustness of findings. Five data sources were used to create a combined state-level longitudinal dataset. ResultsWe did not find significant effects of refundable EITC presence or generosity on unintentional or intentional fatal overdose or SUD prevalence in two-way models. Event study models detected a very slight upward shift in SUD prevalence following refundable EITC implementation (not seen in sensitivity analyses) and no significant effects of EITC implementation on any of the fatal overdose outcomes. ConclusionsEvidence regarding income support programs is being highly sought by policy makers as income support programs have become increasingly popular policy levers since the start of the COVID-19 pandemic. Our study indicates EITC policies likely have no impact on SUD or overdose, however, other income support programs without family restrictions are important to investigate further.

Intentional insulin overdose in a type 2 diabetic patient and depressive disorder

Intentional insulin overdose in a type 2 diabetic patient and depressive disorder

Unveiling potential adverse events associated with escitalopram oxalate: A real-world analysis based FDA adverse event reporting system database.

The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose (n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt (n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin (n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive (n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug's label. While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.

Analysis of drug-drug interactions in spontaneous adverse drug reaction reports from EudraVigilance focusing on psychiatric drugs and somatic medication

IntroductionPatients with severe mental illnesses (SMI) are often exposed to polymedication. Additionally, the risk of somatic diseases is twice as high in patients with SMI as in individuals without a psychiatric disorder. Furthermore, drug–drug interactions (DDI) between psychiatric drugs and somatic medications are a well-known cause of adverse drug reactions (ADR).ObjectivesThe aim of this study was to analyse whether already known DDI related to psychiatric drugs and somatic medication still occur in everyday clinical practice.MethodsTherefore we identified all spontaneous ADR reports contained in the European ADR database EudraVigilance from Germany received between 01/2017 and 12/2021 reported for patients older than 17 years in which antidepressants, antipsychotics and mood stabilizers were reported as suspected/interacting (n= 9,665). ADR reports referring to intentional overdoses and suicide attempts were excluded (n= 9,276 left). We used the ABDATA drug information system in order to identify all potential DDI (pDDI). The identified reports with pDDI were then assessed individually to determine whether the respective DDI occurred.Results 1,271 reports with 728 potentially interacting drugs pairs related to psychiatric drugs and somatic medications with 2,655 pDDI were found. Restricted to potentially interacting drug pairs with more than 10 reports, (i) hyponatremias related to antidepressants and diuretics (n= 362, 32.6%), (ii) bleeding events related to selective serotonin reuptake inhibitors (SSRI) and platelet aggregation inhibitors, anticoagulants or non-steroidal antiinflammatory drugs (NSAID) (n= 295, 17.5%), and (iii) increased beta-blocker effects related to SSRIs and beta-blockers (n= 126, 11.3%) were the most frequently identified pDDI. After individual case assessment, in 33.3% (14/42), 23.7% (45/190) and 17.4% (8/46) of the reports bleeding events related to SSRIs and anticoagulants, SSRIs and platelet aggregation inhibitors and SSRIs and NSAIDs were reported. Hyponatremia was reported in 7.6% (22/289) of the reports related to antidepressants and diuretics and increased beta-blocker effects in 6.9% (8/116) of the reports related to SSRIs and beta-blockers.ConclusionsAccording to our analysis, well-known DDI still occur in the treatment of psychiatric patients with psychiatric drugs and somatic medication. Whenever possible, alternative drug combinations with a lower potential of DDIs may be considered or appropriate monitoring measures should be conducted.Disclosure of InterestNone Declared