Therapeutic monitoring of anti-seizure medications in low- and middle-income countries: a systematic review

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.