Need for a more developmental perspective: QTc prolongation under psychotropic medication

Abstract

not treated appropriately, but several authors suggest that the exact relationship between prolongation of the QTc interval and the risk of TdP remains elusive [6,7]. Nevertheless, there seems to be a broad consensus that QTc interval > 450-500 ms, and/or QTc prolongation > 60 ms should be used as thresholds requiring increased attention in clinical settings. In addition, physicians should consider cardiovascular risk factors when choosing antipsychotic medications and monitor QTc intervals depending on patient and treatment-related risk factors, as is recommended by the German S3 and British NICE clinical guidelines for the treatment of adults with psychosis or schizophrenia [8,9]. Notably, in both cases corresponding recommendations specific for children and adolescents do not exist.There is some discussion as to the general validity of QTc prolongation in the individual patient due to ECG methodological issues (e.g. diurnal variation in the QTc interval) as well as its risk elevation of cardiovascular adverse events. While some authors argue that QTc prolongation is still the best clinical surrogate marker for TdP risk [10], some others criticize this as an oversimplified statement [11] and some even suggest newer surrogate markers (e.g. T peak -T end [12,13]) for ventricular arrhythmogenesis including drug-induced TdP. Furthermore, drug regulatory bodies and pharmaceutical companies have placed restrictions on some antipsychotic drugs which appear to have a low risk of TdP (for example, quetiapine). Conversely, other drugs with clear evidence of risk have the same level of restriction (for example, amisulpride) [6]. In this context, the definition and weighting of the (above mentioned) cardiovascular risk factors and the resulting effective individual risk for a cardiovascular adverse event are discussed controversially. Some admonitory authors call for a more detailed consideration of the risk of the There are several areas of child and adolescent psychiatry for which the quality and quantity of evidence are substantially lower than for psychiatric care of adults [1][2][3][4]. In this context, one of the most frequently asked questions is about the existence of appropriate and well-regulated pediatric psychopharmacological research to generate evidence as a basis for clinical recommendations [5]. Therefore, concerted efforts to facilitate pediatric psychopharmacological research are claimed again and again without noticeable progress probably because of the (still) limited economic perspectives for sponsors and the various ethical and other concerns and obstacles in investigating children and adolescents. But not only the "generation" of data on pediatric psychopharmacology, but also its "summary and critical evaluation" are still limited.In our personal daily clinical experience in child and adolescent psychiatry, there are a handful of diagnostic and treatment recommendations that are based more on somewhat oversimplified statements from publications on adults than on comprehensive and well-balanced consi...

European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part III: pharmacological treatment

“…In general, adverse effects of dopamine receptor antagonists are broad, ranging from extrapyramidal adverse effects including acute dystonia, parkinsonism, and akathisia to metabolic adverse effects including weight gain, type 2 diabetes mellitus, lipid spectra abnormalities, blood pressure changes, fatigue, headache, body temperature dysregulation, hyperprolactinemia, and sexual dysfunction, increase of prolactin levels, and QTc-prolongation as well as ‘behavioral’ changes, such as concentration problems, apathy, anhedonia and sedation, aggression, anxiety, and agitation [ 114 , 115 ]. The limited existing evidence does not allow to predict individual potential adverse effects preceding the start of treatment [ 116 ]. Regarding hyperprolactinemia, antipsychotics with tight D2-binding predictably lead to hyperprolactinemia (“prolactin-raising”), whereas antipsychotics with loose D2-binding and partial agonistic action (e.g., aripiprazole) are considered as “prolactin-sparing” [ 117 ].…”

“…Moreover, questions around how to deal with treatment refractoriness remain unanswered [ 193 ]. The risk of adverse events when using specific agents needs further exploration, e.g., sudden death due to QTc prolongation [ 116 ], hyperprolactinemia and its consequences [ 109 ], and weight gain [ 128 ]. In addition, the questions of optimal treatment duration, as well as long-term outcome after discontinuation of a pharmacological treatment of tics remain unanswered.…”

QT prolongation is over-estimated by Bazett compared to Friderica in Japanese child and adolescent inpatients

“…Roessner et al . (2017) pointed out that the results of ‘non-naturalistic’ studies should be interpreted with caution because participants in safety studies are usually free of many other clinically encountered risk factors, and a baseline QTc value exceeding 450 msec is usually an exclusion criterion (Roessner et al . 2017).…”

“…Clinical trials have the risk of potential selection bias in cohorts with a low risk of QTc prolongation due to exclusion criteria for the baseline of QTc value. Roessner et al (2017) pointed out that the results of 'non-naturalistic' studies should be interpreted with caution because participants in safety studies are usually free of many other clinically encountered risk factors, and a baseline QTc value exceeding 450 msec is usually an exclusion criterion (Roessner et al 2017). A retrospective study tends to have more neutral cohorts without this kind of selection bias.…”

A Neurodevelopment Approach for a Transitional Model of Early Onset Schizophrenia

“…Although in childhood and adolescence, pathological prolonged QT interval, associated to antipsychotic treatment, is not frequently reported [117], quantity and quality of evidence are lower than in adulthood. Thus, a careful monitoring is recommended [118].…”