Clinical utility of therapeutic drug monitoring of antiepileptic drugs

Abstract

ObjectiveTo systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy.MethodsWe searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925.ResultsSixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line.ConclusionsIf optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.

Unanticipated improvement in seizure control in drug-resistant epilepsy- real world observations

“…Third, serum ASM levels were not routinely used to guide dosage adjustments. Prospective studies have failed to show that serum ASM concentrations relaibly correlate with ASM responsiveness [18,19] and the doses reached in the present study were comparable to a treatment protocol utilized in an observational DRE treatment study [11]. Fourth, the senior author's (D.J.C.)…”

“…ASMs are titrated to a target dose rather than a target serum concentration, as therapeutic drug monitoring is not reliably associated with improved clinical outcomes. [18,19] Tolerability is assessed by gradually titrating to an interim dose before increasing further to the target dose. The ASM is retained if it improves seizure frequency or severity.…”

Past, present and future perspectives of therapeutic drug monitoring in India

“…TDM has been used as a tool to optimise pharmacotherapy with antiepileptic drugs despite numerous doubts regarding its efficacy by targeting a “reference range” 27 . Al‐Roubaie et al recently reported in a systematic review of 4 RCT’s, 1 meta‐analysis and 11 quasi‐experimental studies, that TDM did not have significant effects on seizure outcomes but was associated with better seizure control and lesser adverse events 28 . In India, antiepileptics are the most common class of drugs for which TDM is performed as well as available.…”

Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability

“…First, we did not measure serum VPA levels in the rats although we did follow the same oral dosing schedule previously described, 9 which has been shown to achieve a blood level of 180–280 μmol/l and to have anti-seizure effects. 52 Second, we did not undertake a dose–response curve across VPA dosages, which has the theoretical potential to establish if there is a ‘safe’ dosage below which the transcriptional effects of VPA do not occur. This is an important clinical unknown highly relevant to women whose seizures are not controlled by any medication other than VPA.…”