Seizures pregabalin

Outside of the evidence-based guidelines, other pharmacologic treatments are commonly used or avoided. For initial treatment of absence seizures, ethosuximide and valproate are commonly used, not only in the United Kingdom, but also in the United States. Zonisamide may be also used for initial treatment of absence and myoclonic seizures. In absence and myoclonic seizures, carbamazepine, oxcarbazepine, gabapentin, tiagabine, and pregabalin should be avoided, as they have been associated with an exacerbation of these types of seizures. 

Partiai-onset seizures Pregabalin, at doses of 150 to 600 mg/day, has been shown to be effective as adjunctive therapy in the treatment of partial-onset seizures in adults. The total daily dose should be divided and given 2 or 3 times daily. The efficacy and adverse reaction profiles of pregabalin have been shown to be dose related. In general, it is recommended that patients be started on a total daily dose no greater than 150 mg/day (75 mg 2 times a day, or 50 mg 3 times a day). Based on individual patient response and tolerability, the dose may be increased to a maximum dose of 600 mg/day. 

Discontinuation Withdraw pregabalin gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. If pregabalin is discontinued, this should be done gradually over a minimum of 1 week. Pregnancy Category C. 

The story of the discovery of pregabalin (2) began in 1991, when Silverman and Taylor published a paper on the anticonvulsant effect of 3-alkyl GABA analogs (Silverman et ah, 1991). Out of this collection of compounds, 3-isobutyl GABA stood out as the most active analog in the series, which protected mice from seizures induced by corneal electroshock. 

Pregabalin is approved for the adjunctive treatment of partial seizures, with or without secondary generalization controlled clinical trials have documented its effectiveness. It is available only in oral form, and the daily dose ranges from 150 to 600 mg/d, usually in two or three divided administrations. Pregabalin is also approved for use in neuropathic pain, including painful diabetic peripheral neuropathy and postherpetic neuralgia. 

Pregabalin As for gabapentin Well absorbed orally not bound to plasma proteins not metabolized ti/2 6—7 h Partial seizures Toxicity Somnolence, dizziness, ataxia Interactions Minimal... 

A mixture model implicitly assumes that some fraction. (p) of the population has one set of typical values of response, and that the remaining fraction (1 — p) has another set of typical values. In this model, the only difference initially allowed in the typical values between the two groups was the maximal fractional reduction in seizure frequency after treatment with pregabalin, that is, EmaxA EmaxB- Values for these two parameters and the mixing fraction p were estimated. Random interindividual variability effects r i and r 2 were assumed to be normally distributed with zero means and common variance co. The estimation... 

R. Miller, B. Frame, B. Corrigan, P. Burger, H. Bockbrader, E. Garofalo, and R. Lalonde, Exposure-response analysis of pregabalin add-on treatment of patients with refractory partial seizures. Clin Pharmacol Ther 73 491-505 (2003). 

Observational studies Pregabalin has been evaluated in an open 21-week study in 476 adults (mean age 40 years) with partial seizures inadequately controlled with one to three antiepileptic drugs 7% discontinued for lack of efficacy and 12% because of adverse events [247 ]. The three most common adverse reactions were dizziness (17%), somnolence (13%), and weight gain (13%). 

Placebo-coutrolled studies Pregabalin and lamotrigine have been evaluated in 435 patients with refractory partial seizures in a double-blind, randomized, placebo-controlled study (see above under Lamotrigine). 

Baulac M, Leon T, O Brien TJ, Whalen E, Barrett J. A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures. Epilepsy Res 2010 91(1) 10-9. 

Observational studies An open label study of pregabalin for refractory seizures in 136 Mexican patients found that the most common adverse events were somnolence (39.7%), dizziness (16.2%), and weight gain (14%) [139 -]. 

Maschio M, Dinapoli L, Sperati F, Pace A, Fabi A, Vidiri A, et al. Effect of pregabalin add-on treatment on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy a pilot study. Epileptic Disord December 2012 14(4) 388-97. 

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