Topiramate slow dose titration: Improved efficacy and tolerability

Prospective Study of First-choice Topiramate Therapy in Newly Diagnosed Infantile Spasms

“…The mean topiramate dosage of 5.2 mg/kg per day applied in our study is relatively low compared with an older study by Glauser et al, 9 with a mean dosage of 29 mg/kg per day; however, it is similar to a more recent study by Albsoul-Younes et al, 19 who recommended a dosage of 6 to 12 mg/kg per day. Although only 9 patients (16.6%) were spasm free in our study as a result of topiramate monotherapy compared with 3 patients (38%) in the study by Glauser et al, 9 the overall results of all treatments, including the combination of topiramate with nitrazepam and valproic acid, are rather satisfying, with 31 patients (57.4%) reaching spasm-free status and 13 patients (24%) reaching a spasm reduction of more than 30%.…”

“…No acute or long-term idiosyncratic organ toxicity was observed with topiramate, which is consistent with the safety profile in earlier studies. 11,16,19,21,22 In addition, metabolic acidosis may occur, 21,23,24 and approximately 1.5% of patients treated with topiramate develop kidney stones in adult 25 and patients with metabolic acidosis, but they have not been registered in our study according to the observation of legal caregivers and the long-time follow up. The results were similar to those of the study by Ritter et al 26 In newly diagnosed patients with infantile spasms in our study, the parents were often not patient enough to wait for topiramate escalation to reach the target dose.…”

“…Moreover, children younger than 4 years may have a particularly good tolerability of topiramate, 18 especially if slow and progressive dose titration is applied. 10,18,19 Generally, topiramate proves to be well tolerated and safe; the adverse effects tend to occur early during treatment and to be not life threatening. 14,21 In our study, 14 patients (26%) revealed adverse events.…”

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…[78,79] For this reason, particularly in the paediatric setting, special care should be taken not to exceed the recommended initial dose and speed of titration. A slow titration may also minimize CNS adverse effects by allowing pharmacodynamic tolerance and early detection of subtle or prodromal signs, which can, in turn, indicate that adverse effects might worsen with further dose increase.…”

The Safety and Tolerability of Newer Antiepileptic Drugs in Children and Adolescents

“…Most adverse effects are transient, and slower titration at 2-week intervals may improve tolerability. [235,292] Of note, one study group did not find behavioural and cognitive adverse effects in children to be related to the rate of titration or final dose. [255] Two studies reported no relationship between serum topiramate concentrations and adverse effects in children and adults.…”