Levetiracetam monotherapy

Alsaadi TM, Koopmans S, Apperson M, Farias S. Levetiracetam monotherapy for elderly patients with epilepsy. Seizure 2004 13(1) 58-60. 

In a pooled analysis of safety data from double-bUnd, placebo-controUed add-on trials of levetiracetam (1-3 g/ day) in adults with refractory partial seizures, adverse events occurring in at least 3% of patients and with at least 3% higher incidence in the active treatment group were tiredness (14 versus 10%), somnolence (15 versus 10%), dizziness (9 versus 4%), and common cold or upper respiratory tract infections (13 versus 7%) (11). The proportions of patients requiring withdrawal of treatment or dosage reduction owing to adverse events were 15% with levetiracetam and 12% with placebo. The efficacy and tolerability of levetiracetam monotherapy in refractory partial seizures have been studied in a double-blind, pla-cebo-controUed study in 286 patients (12). Adverse events that were more common with levetiracetam and that occurred in more than 5% of cases included weakness, infection, and somnolence. Of 181 patients who took levetiracetam, 36 completed the study compared with only 10 of 105 who took placebo. The tolerability and efficacy of levetiracetam, 2 or 4 g/day, as add-on therapy have been studied in 119 patients with refractory epilepsy (13). Somnolence was the most common reason for withdrawal and occurred more often with levetiracetam than placebo, as did weakness. Somnolence was more common with the higher dose, which was not more effective than... 

Liver A 58-year-old woman with epilepsy developed a significant increase in gamma-glutamyltransferase activity while taking levetiracetam monotherapy [215 ]. Levetiracetam was progressively withdrawn and replaced with lamotrigine 200 mg/day, and over the next 2 months, the yGT activity gradually fell. 

Maschio M, Dinapoli L, Sperati F, Pace A, Fabi A, Vidiri A, Muti P. Levetiracetam monotherapy in patients with brain tumor-related epilepsy seizure control, safety, and quality of life. J Neurol 2010 257(11) 1939-40. 

Broli M, Provini F, Naldi I, Bisulli F, Sama C, Baruzzi A, Tinuper P, Riva R. Unexpected gamma glutamyltransferase rise increase during levetiracetam monotherapy. Epileptic Disord 2010 12(1) 81-2. 

Observational studies Levetiracetam monotherapy has been investigated in 35 patients with late-onset post-stroke seizures in a prospective open study [178 ]. At a mean follow-up period of 18 months, 27 patients had achieved seizure freedom. Four of 35 patients stopped taking levetiracetam because of severe adverse events drowsiness with gait disturbance and aggressive behavior in two cases, and severe psychomotor agitation with aggressive behavior in the other two patients. 

Comparative studies Levetiracetam versus phenytoin Levetiracetam monotherapy has been compared with phenytoin for postoperative control of glioma-related seizures in a randomized pilot study [181 ]. Over 13 months, 29 patients were randomized in a 2 1 ratio to start levetiracetam within 24 hours of surgery or to continue phenytoin therapy. Similar percentages of patients were seizure-free after 6 months of treatment. Reported adverse effects at 6 months were dizziness (0% levetiracetam, 14% phenytoin), difficulty with coordination (0% versus 29%), depression (7% versus 14%), lack of energy or strength (20% versus 43%), insomnia (40% versus 43%), and mood instability (7% versus 0%). No adverse effect resulted in hospitalization or withdrawal from the study. 

Lim DA, Tarapore P, Chang E, Burt M, Chakalian L, Barbaro N, Chang S, Lamborn KR, McDermott MW. Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy a randomized phase II pilot study. J Neurooncol 2009 93(3) 349-54. 

Side effects. Detailed safety studies show that levetiracetam is well tolerated, the most frequent side effects reported being somnolence, asthenia and dizziness. To date, levetiracetam would appear to be a highly effective new antiepileptic drug with an excellent safety and tolerability profile. Few drug interactions have been reported so far. The efficacy and safety of the drug have been established as add-on therapy for refractory partial onset seizures with or without secondary generalization and there is now evidence of its efficacy in monotherapy. 

Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures a multicenter, double-bUnd, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia 2000 41(10) 1276-83. 

I Place in Therapy. Currently, levetiracetam is indicated for patients with partial seizures who have failed initial therapy. Its role as monotherapy for partial seizures and as adjunctive treatment for generalized seizures remains to be clarified. 

The place in therapy of the newer anticonvulsants, such as gabapentin, levetiracetam, tiagabine, topiramate, and zon-isamide, is controversial. Many clinicians consider these agents to be less effective than established mood stabilizers based on initial studies and avoid them for monotherapy in bipolar disorder. 

A double-blind, placebo-controlled trial of adults with refractory partial seizures demonstrated that addition of levetiracetam to other antiseizure medications was superior to placebo. Insufficient evidence is available with respect to use of levetiracetam as monotherapy for partial or generalized epilepsy. 

In a retrospective study in 218 patients, mostly adults, with localization-related epilepsy, taking levetiracetam as adjunctive therapy or monotherapy for up to 36 months, the retention rates at 6, 12, 24 and 36 months after the start of levetiracetam treatment were 92%, 75%, 60%, and 54% respectively [205 ]. 

In six neonates (body weight over 2000 g, gestational age over 30 weeks) in a prospective pilot study on the use of oral levetiracetam as monotherapy in the treatment of neonatal seizures the dose was increased by 10 mg/kg day over 3 days [206 ]. There were no clear adverse events during the study. There was mild sedation during titration in one neonate taking concomitant phenobarbital. 

Endocrine The effects of levetiracetam and valproic acid monotherapy on sex steroid hormone profiles in prepubertal children have been investigated in 30 subjects [325 ]. Ten took levetiracetam, 10 took valproate, and 10 were healthy controls. Those who took valproate had significantly higher androstenedione concentrations than those who took levetiracetam and controls. All other reproductive endocrine hormones were similar among the groups. 

Levetiracetam versus CBZ Levetiracetam and CBZ were compared in 106 patients with poststroke seizures. There was no significant difference in seizure control. There were significantly fewer adverse effects with levetiracetam versus CBZ attention deficit, frontal executive functions, and functional scales were significantly worse in the CBZ group [29 ]. A separate randomized unblinded study compared levetiracetam and CBZ as monotherapy for seizures in 992 patients. More adverse effects were reported in the CBZ group, which resulted in more patients discontinuing the study (19% vs 10%) [30 ]. 

Chung S, Ceja H, Gawtowicz J, Avakyan G, McShea C, Sduemann J, et al. Levetiracetam extended release conversion to monotherapy for the treatment of patients with partial-onset seizures a double-blind, randomised, multicentre, historical control study. Epilepsy Res August... 

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