Aim: The Norwegian Association for Clinical Pharmacology in their
National Guidelines decreased therapeutic range (TR) of topiramate (TPM)
from 5-20 mg/L to 2-10 mg/L. The objective of this study is to ascertain
which TR produces better clinical outcomes. Methods: Data source were
request forms for routine therapeutic drug monitoring of TPM.
Concentration dependent adverse drug reactions (ADRs) were evaluated in
1,721 samples taken pre-dose. Seizure frequency analysis was performed
in 294 samples of monotherapy. Statistics: Prism 5.0, GraphPad Instatt:
Mann–Whitney U test for median plasma level (PL). χ2-test for seizure
frequency and for distribution of PL according to TR 5-20 mg/L and
intervals <2, 2-5, 5-10, 10-20, >20 mg/L.
Results: Better seizure control was found in children both in whole
cohort (without seizure 49% vs 37% adults), as well as in monotherapy
(56% vs 44%), in children with PL 5-20 mg/L vs 5 mg/L (65% vs 44%)
and in children with PL 5-10 mg/L vs <2 mg/L. Seizure-free
children had higher PL than those with seizure yearly: median (lower,
upper quartile) [mg/L]: 5.5 (3.4-6.5) vs 4.7 (4.3-7.95). No
difference was found in adults. Seizure control was poorer in all
patients with PL <2 mg/L compared to 5-10 mg/L; and 10-20
mg/L; further in PL within 5-10 mg/L vs 10-20 mg/L; and in the period
2003-2005. ADRs reported in 38 samples (2.8%) were without relation to
PL. Conclusions: Change of TR is not recommended.