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Categorization of psychotropic medications according to the reported risks for induction of cardiac arrhythmia Drug EMA FDA Micromedex Maudsley Arizona Thorough QT study The weighted recommendations
Source publication
Several drugs used in the treatment of mental diseases are associated with an increased risk of sudden cardiac death (SCD). A general cause-relationship between the intake of these drugs and SCD is unattainable, but numerous case reports of drug-induced malignant arrhythmia and epidemiological studies, associating the use of specific drugs with SCD...
Contexts in source publication
Context 1
... proposal was developed in collaboration between the Danish Society of Cardiology and the Danish Psychiatric Society 21 (see Appendix). Table 2) is chosen, assessment of the cardiac risk profile is recommended. If cardiac risks are identified-the cardiac risk factors should be optimized and/or a drug with a more favourable risk profile should be chosen. ...
Context 2
... three categories ( Table 1) are modified from qtdrugs.org-now http://crediblemeds.org: drugs with neither QT-prolongation nor TdP risk corresponds to Class A. The category 'possible TdP risk' corresponds to Class B. The categories 'drugs to be avoided by congenital long QT', 'Drugs with conditional TdP risk', and 'drugs with known TdP risk' are merged into Class B*. In Table 2, psychotropic drugs are classified according to these categories. The accessibility of TQT studies was investigated for each drug through searching the following sources: the summery of products characteristics, www.clinicaltrials.gov ...
Context 3
... class of recommendation ( Table A1) and class of evidence (Table A2) for the present guideline recommendations are given in Table A3 (see Appendix). ...
Context 4
... decision to commence treatment with psychotropic medica- tions includes several steps: evaluation of the severity of the psychi- atric condition and the need for pharmaco-therapy; selection of the appropriate psychotropic medication-at the recommended dose; assessment of the cardiac risk associated with the chosen medi- cation; if a class A drug has been chosen (Table 2), the treatment can be commenced without any further cardiac risk assessment. If a class B or B* drug ( Table 2) is chosen, assessment of the cardiac risk is needed according to the proposed algorithm ( Figure 1); if cardiac risks are identified, the cardiac risk factors should be optimized and/or a drug with a more favourable risk profile should be chosen if possible. ...
Context 5
... decision to commence treatment with psychotropic medica- tions includes several steps: evaluation of the severity of the psychi- atric condition and the need for pharmaco-therapy; selection of the appropriate psychotropic medication-at the recommended dose; assessment of the cardiac risk associated with the chosen medi- cation; if a class A drug has been chosen (Table 2), the treatment can be commenced without any further cardiac risk assessment. If a class B or B* drug ( Table 2) is chosen, assessment of the cardiac risk is needed according to the proposed algorithm ( Figure 1); if cardiac risks are identified, the cardiac risk factors should be optimized and/or a drug with a more favourable risk profile should be chosen if possible. In case of structural heart disease, QT prolongation, elec- trolyte disturbances, or cardiac symptoms referral to a cardiologist should be considered. ...
Similar publications
Acquired long QT syndrome, mostly as a result of drug block of the Kv11. 1 potassium channel in the heart, is characterized by delayed cardiac myocyte repolarization, prolongation of the T interval on the ECG, syncope and sudden cardiac death due to the polymorphic ventricular arrhythmia Torsade de Pointes (TdP). In recent years, efforts are underw...
Long QT syndrome is a heart rhythm disorder with a prolonged QT interval which can result in a torsade de pointes tachycardia and ventricular fibrillation leading to sudden cardiac death. To date, there are 14 subtypes known with multiple different genes and locations of the mutation causing the disease that is either inherited or caused by de-novo...
Symptomatic long QT syndrome in pediatric patients is a life-threatening condition. Sometimes, this pathology can be misdiagnosed and erroneously managed as generalized epilepsy due to similar clinical manifestations. The presented case discusses a 13-year-old female patient with generalized epilepsy since the age of 4, admitted for two episodes of...
Citations
... É importante destacar que pacientes com DCVs e depressão requerem uma abordagem médica otimizada e específica buscando avaliar seu perfil de risco CV, orientar a escolha de medicamentos efetivos que não agravem e/ou aumentem os riscos de morbimortalidade e permita acompanhar adequadamente as intercorrências e efeitos adversos (FANOE et al., 2014;KAHL, 2018). ...
... Os EACV requerem dos médicos o conhecimento dos riscos inerentes a cada tipo específico de AD e riscos de possíveis associações medicamentosas. Também é fundamental a implementação de avaliações de triagem necessárias para redução de riscos tais como, a realização de eletrocardiograma (ECG), monitoração da pressão arterial, peso corporal e parâmetros eletrolíticos e metabólicos (FANOE et al., 2014;MANOLIS;MANOLIS;MANOLIS, 2019). ...
... Embora exista a possibilidade de efeitos adversos gerais, cardiovasculares e até risco de MSC com o uso de AD, esses medicamentos são geralmente bem tolerados e necessários para o tratamento da depressão e diversas outras doenças. Dessa forma, apresentamos nessa sessão um conjunto de orientações, preocupações e condutas, baseadas em informações de estudos clínicos e diretrizes (de tratamento e manejo clínico), visando a segurança do paciente bem como, a prevenção e o controle de possíveis efeitos adversos (FANOE et al., 2014;KAHL, 2018;KAHL;STAPEL;CORRELL, 2022). ...
Introduction: Treatment of depression / depressive disorder requires effective therapeutic agents, well tolerated and with a low rate of complications and adverse events. However, some antidepressants(AD)have been associated with an increased risk of sudden cardiac death (SCD) and general and cardiovascular adverse events, important in daily clinical practice. Objective: Raise possible adverse cardiovascular events and risk of SCD associated with AD use in adult patients. Additionally, investigate general adverse effects, action mechanisms and main risk drug interactions with AD and guidelines for monitoring / optimized clinical management of patients. Methodology: integrative review aiming, from scientific literature, to collect information regarding the objectives of this review in the main databases: PubMed; Lilacs; Google Scholar; Brazilian´s Health Ministry. Selection criteria were: meta-analysis articles, systematic review, review, guidelines, consensus and observational studies (cohort studies, case-control or cross-sectional studies) and randomized control studies, published between 2010 and April 2023. Results: 173 publications were selected allowing verify which patients had high risk for developing adverse cardiovascular events associated with the use of AD: elderly; preexisting cardiovascular risk factors; patients with comorbidities (mainly acute and/or chronic coronary artery disease, heart failure and renal failure); CYP450 poor/slow metabolizers; previous history of ventricular arrhythmias or syncope; carriers of channelopathies; family history of long QT syndrome, sudden death, diabetes mellitus and arterial hypertension; polypharmacy; AD use in high doses; electrolyte abnormalities (eg: hypokalemia, hypomagnesaemia, etc.). Studies demonstrated that selective serotonin reuptake inhibitors had a relative risk of SCD of 2.39 (95%CI 1.20-4.80) while tricyclic ADs risk ranging from 1.69 (95%CI 1.14-2.50) at 4.37 (95%CI 1.23-15.60). We summarized the risk information in tables and charts with recommendations from main studies and guidelines regarding the clinical management, monitoring and management of adverse events. Conclusion: Although the use of ADs has recognized general and cardiovascular adverse effects, their risks shouldn´t deprive patients of appropriate therapy for psychiatric disorders, including those with cardiovascular diseases. The available literature data allow adopting screening of patients who need the use of DA, monitoring treatment and adopting effective preventive measures to reduce the risk of possible complications.
... Therefore, they are classified in risk group 1 (www.crediblemeds.org). According to another classification, they belong to the category Class B, which means that there is an associated risk of arrhythmia and a "possible TdP risk" (Fanoe et al. 2014). ...
After administration of the serotonergic antidepressant citalopram (CIT) to beagle dogs, they may experience severe convulsive attacks in relation with considerably higher plasma concentrations of the metabolite didesmethyl-CIT (DDCIT), when compared to those in humans medicated with CIT. This pilot study aimed at determining the role of cytochrome P-450 (CYP450) isozymes in the in vitro metabolism of CIT to desmethyl-CIT (DCIT), and of DCIT to DDCIT in the liver microsomes of a single beagle dog. The incubations with racemic CIT or DCIT reveal a high affinity enzyme with Km between 0.3 µM and 1.4 µM for S- and R-DCIT and S- and R-DDCIT productions, respectively. In comparison to human enzymes, the intrinsic clearance values of this high affinity enzyme are between 15 µL/(min x mg of protein) and 52 µL/(min x mg of protein), i.e. very high. In vitro experiments with inhibitors suggest that CYP2D15, which shows analogy with human CYP2D6, is by far the main CYP450 isozyme involved in the production of DCIT and DDCIT whereas CYP3A12 and CYP2C21/41 showed a weak implication. These observations partly explain why in humans, plasma concentrations of the toxic DDCIT are considerably lower than those observed in dogs, after administration of CIT.
... Tricyclic antidepressants can cause life-threatening side effects such as QTc prolongation, cardiac arrhythmias, and epileptic seizures, especially at high doses (Fanoe et al., 2014;Johannessen Landmark et al., 2016). Therefore, tricyclic antidepressant abuse can be fatal. ...
Although antidepressants are theoretically safe, the abuse of antidepressant drugs is increasingly taking place in the literature. Most cases had a history of concomitant alcohol or substance use. We present a 49-year-old female patient with a diagnosis of schizophrenia who had a clomipramine misuse history without alcohol or substance addiction. The patient gradually increased the clomipramine dose without the doc-tor's advice. She used clomipramine in higher doses than usual and often requested the doctors to prescribe it to relieve her complaints. Patients with a history of psychotic illness may abuse anticholinergics to reduce existing anhedonia. Therefore, our patient may have used clomipramine to alleviate the anhedonia she experienced. Tricyclic antidepressant abuse can be fatal so it is important to recognize this phenomenon.
... Lack of a clinically relevant effect of antipsychotic drugs on the QTc interval is important because patients treated with antipsychotic drugs have been reported to have an increased risk of sudden cardiac death. [23][24][25][26] Several antipsychotic drugs have been shown to prolong the QTc interval, 27,28 and drug-induced QTc prolongation is associated with higher risk of cardiac arrhythmias, such as torsades de pointes, which can lead to sudden death. 29,30 In this study, concentration-QTc analysis was used as the primary analysis, which enabled the assessment of QTc changes over a wide range of concentrations. ...
This study (NCT04369391) evaluated the effects of ulotaront (SEP-363856), a novel trace amine-associated receptor 1 (TAAR1) agonist in development for schizophrenia, on electrocardiogram parameters. Study design was a randomized, single-dose, 3-period crossover (ulotaront 150 mg, placebo, moxifloxacin 400 mg). Sixty subjects with schizophrenia completed all periods. Ulotaront had no clinically relevant effect on heart rate, PR interval, or QRS duration. In by-time-point analysis (secondary analysis), the upper bound of the 2-sided 90% CI for ΔΔQTcF was below 10 ms at all time points for ulotaront. In concentration-QTc analysis (primary analysis), a linear mixed-effects model with ulotaront and its major metabolite SEP-383103 was selected as the primary model based on prespecified criteria. Effect on ∆∆QTcF exceeding 10 ms can be excluded within observed ranges of ulotaront and SEP-383103 plasma concentrations up to ~574 and ~272 ng/mL, respectively. The upper bound of 90% CI for ΔΔQTcF can be predicted to be below 10 ms at the highest anticipated clinical exposure, currently defined as steady-state mean Cmax at ulotaront 100 mg/day in CYP2D6 poor metabolizers, ~416 and ~211 ng/mL for ulotaront and SEP-383103, respectively. Assay sensitivity was demonstrated by the QTc effect caused by moxifloxacin. In conclusion, ulotaront is unlikely to cause clinically relevant QTc prolongation in patients with schizophrenia at the anticipated maximum therapeutic dose.
... 3) классификации, предложенной Fanoe S и соавт. в 2014 году [67], т. к. они вызывают удлинение интервала QT, либо об их влиянии на интервал QT нет данных. Это заставляет практикующих врачей с осторожностью относиться к длительному назначению антиконвульсантов и предполагать риск развития LQTS и, как следствие, возможный СВС (см. ...
... С риском антиконвульсант-индуцированного LQTS ассоциированы (рис. 5): гены, ответственные Таблица 3 Table 3 Classification of psychotropic drugs according to the risk of prolongation of the QT interval and the development of arrhythmia [2,67] Категория Характеристика ...
Anticonvulsants or antiepileptic drugs (AEDs) are widely used for various neurological and psychiatric diseases and are often prescribed for a long period. In this regard, the issue of their safety profile is acute, including risk assessment for the development of life-threatening conditions and adverse drug reactions (ADRs). From the point of view of personalized medicine, it is important to develop an interdisciplinary approach to the development of a new strategy for a personalized approach to predicting AED-induced prolongation of the QT interval as one of the most unfavorable prognostic cardiac ADRs (including sudden death syndrome — SDS). We searched the databases of full-text publications for the period from 2012 to 2022 for keywords and their combinations. We have discovered and systematized monogenic and multifactorial forms of long QT syndrome (LQTS) and candidate genes that slow down AEDs metabolism in the liver. Identification of risk alleles of single nucleotide variants (SNV) of candidate genes predisposing to the development of AED-induced LQTS and SDS will allow adjusting the choice and dosage of these drugs and preventing the development of the ADR, which will improve the quality of life and help prevent SDS in patients with mental and neurological disorders
... Medical history, medication history The presence of comorbidities increases cardiac risk. Psychotropic medications, including antipsychotics and antidepressants can adversely affect the heart [80]. as clinically indicated, including new or changing physical symptoms, rapid weight loss or gain, or a history of under-reporting symptoms [22]. ...
... The QT interval prolongs at slower heart rates and shortens at faster heart rates [80]. Measurement of the QT interval is therefore normalised or "corrected" to a heart rate of 60 bpm known as the corrected QT interval (QTc) [80]. ...
... The QT interval prolongs at slower heart rates and shortens at faster heart rates [80]. Measurement of the QT interval is therefore normalised or "corrected" to a heart rate of 60 bpm known as the corrected QT interval (QTc) [80]. Use of automated QTc readings generated by the ECG machine may be feasible where the ECG is otherwise normal [80]. ...
Background
Eating disorders (EDs) are serious conditions predominantly affecting adolescents and young adults (AYAs) and pose a considerable threat to their health and wellbeing. Much of this increased morbidity and mortality is linked to medical compromise, especially cardiovascular abnormalities. Rates of presentation to both community and inpatient medical settings have increased in all age groups following the Covid-19 pandemic and subsequent “lockdowns”, with patients presentations being more medically compromised compared to previous years. This has implications for clinicians with regard to the performance of competent cardiovascular assessments and management of findings.
Aims
This paper is a practical resource for clinicians working with AYAs in whom EDs may present. It will provide a brief summary of the physiological context in which cardiovascular complications develop, systematically outline these complications and suggest a pragmatic approach to their clinical evaluation.
Methods
Relevant literature, guidelines and academic texts were critically reviewed. Conclusions were extracted and verified by a Child and Adolescent Psychiatrist and Adolescent Paediatrician, with suitable expertise in this clinical cohort.
Conclusions
The cardiovascular complications in EDs are primarily linked to malnutrition, and patients presenting with Anorexia Nervosa are most often at greatest risk of structural and functional cardiac abnormalities, including aberrations of heart rate and rhythm, haemodynamic changes and peripheral vascular abnormalities. Other cardiovascular abnormalities are secondary to electrolyte imbalances, as seen in patients with Bulimia Nervosa. More recently defined EDs including Avoidant/Restrictive Food Intake Disorder and Binge Eating Disorder are also likely associated with distinct cardiovascular complications though further research is required to clarify their nature and severity. Most cardiovascular abnormalities are fully reversible with nutritional restoration, and normalisation of eating behaviours, including the cessation of purging, though rare cases are linked to cardiac deaths. A detailed clinical enquiry accompanied by a thorough physical examination is imperative to ensure the medical safety of AYAs with EDs, and should be supported by an electrocardiogram and laboratory investigations. Consideration of cardiovascular issues, along with effective collaboration with acute medical teams allows community clinicians identify those at highest risk and minimise adverse outcomes in this cohort.
... In many respects, the risk of cardiac complications from APs is genetically determined (Tables 3 and 4). As such, psychiatrists and general practitioners should be in a position to assess and manage the potential risk of LQTS and other cardiac arrhythmias and conduction disorders caused by APs [88]. ...
... Fanoe et al. [88] proposed classifying drugs used in psychiatry into three categories according to the reported effects at therapeutic plasma levels on the QT interval, the induction of cardiac arrhythmias, and conduction disturbances. This study made the predominant distinction between drugs with no risk of cardiac arrhythmias and conduction disorders (Class A drugs) and drugs with some degree of risk (Class B drugs). ...
... The latter group was further subdivided into class B* drugs ( Table 5). APs that are best avoided in patients with congenital QT interval prolongation, with a conditional risk of TdP, and those with a known risk of TdP were compiled into class B* [2,87,88]. LQTS is an important risk factor for the development of TdP, which, in turn, can lead to ventricular fibrillation and SDS [89]. The relationship between AP-induced LQTS and TdP frequency is not direct [87,90,91], since many factors and comorbid conditions can increase or decrease the risk of these iatrogenic effects [90,[92][93][94]. ...
Antipsychotics (AP) induced prolongation of the QT interval in patients with schizophrenia (Sch) is an actual interdisciplinary problem as it increases the risk of sudden death syndrome. Long QT syndrome (LQTS) as a cardiac adverse drug reaction is a multifactorial symptomatic disorder, the development of which is influenced by modifying factors (APs’ dose, duration of APs therapy, APs polytherapy, and monotherapy, etc.) and non-modifying factors (genetic predisposition, gender, age, etc.). The genetic predisposition to AP-induced LQTS may be due to several causes, including causal mutations in the genes responsible for monoheme forms of LQTS, single nucleotide variants (SNVs) of the candidate genes encoding voltage-dependent ion channels expressed both in the brain and in the heart, and SNVs of candidate genes encoding key enzymes of APs metabolism. This narrative review summarizes the results of genetic studies on AP-induced LQTS and proposes a new personalized approach to assessing the risk of its development (low, moderate, high). We recommend implementation in protocols of primary diagnosis of AP-induced LQTS and medication dispensary additional observations of the risk category of patients receiving APs, deoxyribonucleic acid profiling, regular electrocardiogram monitoring, and regular therapeutic drug monitoring of the blood APs levels.
... Although we did not include information about psychotropic medications in the present study because of the inherent limitation of our dataset, psychotropic medications can also affect the arrhythmia risk [55]. Among various types of psychotropic drugs, the antipsychotic drug acts as a trigger factor leading to autonomic dysregulation and results in the occurrence of AF [56,57]. ...
Background
It is unclear whether mental disorders are an independent risk factor for atrial fibrillation (AF) in patients with diabetes. We aimed to investigate whether patients with diabetes who have mental disorders have an increased risk for AF.
Methods
Using the Korea National Health Insurance Service database, we enrolled 2,512,690 patients diagnosed with diabetes without AF between 2009 and 2012. We assessed five mental disorders: depression, insomnia, anxiety, bipolar disorder, and schizophrenia. Newly diagnosed AF was identified during the follow-up period, and multivariate Cox regression analysis was performed.
Results
Among the 2,512,690 patients (mean age 57.2 ± 12.3 years; 60.1% men), 828,929 (33.0%) had mental disorders. Among the five mental disorders, anxiety (68.1%) was the most common, followed by insomnia (40.0%). During a median follow-up duration of 7.1 years, new-onset AF was diagnosed in 79,525 patients (4.66 per 1,000 person-years). Patients with diabetes who had mental disorders showed a higher risk for AF (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.17–1.21; p-value < 0.001). Depression, insomnia, and anxiety were significantly associated with higher risk for AF (adjusted HR [95% CI]: 1.15 [1.12–1.17], 1.15 [1.13–1.18], and 1.19 [1.67–1.21], respectively; all p-values < 0.001), whereas bipolar disorder and schizophrenia were not.
Conclusions
Mental disorders, especially depression, insomnia, and anxiety, were associated with an increased risk for AF in patients with diabetes. Greater awareness with a prompt diagnosis of AF should be considered for patients with both DM and mental disorders.
... Administration, CredibleMeds.org, Micromedex, and the Maudsley prescribing guideline(Fanoe et al. 2014). Based on an analysis of data from these sources, the authors have classified the psychotropic drugs according to their risk to induce cardiac arrhythmias into three categories(Fanoe et al. 2014). ...
... Micromedex, and the Maudsley prescribing guideline(Fanoe et al. 2014). Based on an analysis of data from these sources, the authors have classified the psychotropic drugs according to their risk to induce cardiac arrhythmias into three categories(Fanoe et al. 2014). The category with the highest risk included neither paliperidone nor amisulpride. ...
... Furthermore, we included only the oral formulations of the drugs with few exceptions. This may explain why haloperidol was not among the drugs with the highest risk based on our analysis; because this risk is mostly related to the intravenous application of the drug(Fanoe et al. 2014). Several other studies have also shown that haloperidol is a very critical drug regarding its potential to induce severe forms of cardiac arrhythmias even after oral application. ...
... The unknown risk of arrhythmia should be weighed against risk of undertreating anxio-depressive disorders. 108,109 TCAs (eg, amitriptyline, clomipramine, imipramine) Sodium channel blockade: type IA antiarrhythmic effect causing electric conduction delay with prolongation of PR and QRS Potassium channels blockade: QTc prolongation (worse than SSRIs) 107 α 1 /α 2 -Adrenergic receptor blockade and anticholinergic effects: orthostatic hypotension and sinus tachycardia ...
Although resilience and high quality of life are demonstrated by many individuals with congenital heart disease, a range of significant psychological challenges exists across the life span for this growing patient population. Psychiatric disorders represent the most common comorbidity among people with congenital heart disease. Clinicians are becoming increasingly aware of the magnitude of this problem and its interplay with patients’ physical health, and many seek guidance and resources to improve emotional, behavioral‚ and social outcomes. This American Heart Association scientific statement summarizes the psychological outcomes of patients with congenital heart disease across the life span and reviews age-appropriate mental health interventions, including psychotherapy and pharmacotherapy. Data from studies on psychotherapeutic, educational‚ and pharmacological interventions for this population are scarce but promising. Models for the integration of mental health professionals within both pediatric and adult congenital heart disease care teams exist and have shown benefit. Despite strong advocacy by patients, families‚ and health care professionals, however, initiatives have been slow to move forward in the clinical setting. It is the goal of this scientific statement to serve as a catalyst to spur efforts for large-scale research studies examining psychological experiences, outcomes, and interventions tailored to this population and for integrating mental health professionals within congenital heart disease interdisciplinary teams to implement a care model that offers patients the best possible quality of life.
