Background: The treatment gap for epilepsy is large in low- and middle-income countries (LMICs) and the effectiveness and safety of the available anti-seizure medication (ASMs) is not fully understood. We systematically reviewed available evidence on therapeutic drug monitoring (TDM) of ASM in LMIC.
Methods: We searched four main databases (PubMed, Psych-Info, CINAHL and Embase) up to 31 st December 2020, with eligible articles screened using a PRISMA checklist and a set of exclusion and inclusion criteria. Full texts were examined to evaluate the extent and practice of TDM in LMICs. Analyses were performed using Stata 13 and descriptive statistics were used to pool median distribution of TDM across studies.
Results: Of the 6,309 articles identified in the initial search, 65 (1.0%) met the eligibility criteria. TDM of ASMs was mostly done to assess toxicity (42.8%), but rarely to monitor adherence (9.0%). TDM differed by economic status and infrastructural status with majority of the studies coming from Europe (53.8%) and upper-middle-income countries (87.6%). First generation ASMs (82.3%) were more likely to be monitored than second generation ASMs (17.6%) and carbamazepine was the most frequently monitored drug. Fluorescence Polarization Immunoassay (FPIA) was the most common technique used for TDM (41.5%) followed by High-Performance Liquid Chromatography (HPLC) (16.9%). In addition, FPIA was the cheapest method of TDM based on approximated costs ($1000, TDx system). Assay validation and quality control were reported variably, and reference ranges used during TDM of ASMs were relatively uniform.
Conclusions: TDM is mostly done to evaluate ASM toxicity, but rarely for other reasons such as evaluating adherence or assessing clinical efficacy. There is a need for more investment in comprehensive and targeted TDM in LMICs when initiating treatment, switching therapies, adding or removing ASM and evaluating treatment response and safety of both first generation and second generation ASMs.
Keywords: ASM; LMICs; TDM; Therapeutic drug monitoring; anti-seizure medication; low- and middle-income countries; resource-limited settings.
The number of people with epilepsy who do not have access to treatment is high in low- and middle-income countries (LMICs) and the effectiveness and safety of the available medication for epilepsy is not fully understood. We systematically reviewed available evidence on therapeutic drug monitoring (TDM), i.e. measuring medication levels to ensure they are within the recommended ranges in a LMIC. We searched four main databases (PubMed, Psych-Info, CINAHL and Embase) up to 31st December 2020, with eligible articles screened using a PRISMA checklist and a set of criteria tailored to our study objectives. Full texts were examined to evaluate the extent and practice of TDM in LMICs. Analyses were performed using Stata 13 and we used statistical methods to describe the distribution of TDM across studies. Of the 6,309 articles identified in the initial search, 65 (1.0%) met the set criteria for inclusion. Measurement of medication levels was mostly done to check for side effects (42.8%), but rarely to ensure if patients were taking their medication as prescribed (9.0%). Distribution differed by economic status with the majority of the studies coming from Europe (53.8%) and upper-middle-income countries (87.6%). Older medications for epilepsy (82.3%) were more likely to be monitored than newer drugs (17.6%), with carbamazepine being the most frequently measured drug. A laboratory method called Fluorescence Polarization Immunoassay was the most common (41.5%) and affordable (costing about $1000). Reference ranges for medication levels used during TDM were relatively uniform. We concluded that TDM was rarely done when evaluating medication adherence or clinical efficacy. Therefore, there is a need for more investment in comprehensive and targeted TDM in LMICs when initiating treatment, switching therapies, adding or removing medications and evaluating treatment response and safety of old and newer medications for epilepsy.
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