Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers.
BACKGROUND
The adverse effects of the antiepileptic drugs (AEDs) originally developed are well known, while those of the newer AEDs remain unclear.


OBJECTIVE
To investigate clinical, cognitive, and neurophysiologic effects of carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers.


METHODS
A double-blind crossover study was conducted in 10 volunteers. Eight-day treatment with carbamazepine, oxcarbazepine, levetiracetam, or placebo was administered in random order. Drug doses were titrated gradually to the daily target doses on day 7: carbamazepine 800 mg, oxcarbazepine 1200 mg, and levetiracetam 1500 mg. At baseline and at the end of each treatment period, participants underwent cognitive and neurophysiologic assessment. A washout period of 14 days between treatment periods was conducted.


RESULTS
More adverse events were self-reported with carbamazepine (63%) than the other treatments (oxcarbazepine 12%, levetiracetam 20%, placebo 5%; p < 0.001 between the 4 groups). Carbamazepine induced the greatest motor slowing (p = 0.002), followed by oxcarbazepine (p = 0.01). Levetiracetam left baseline motor speed unchanged. All AEDs increased attention span from baseline values as shown on the Stroop test. Quantitative electroencephalogram (EEG) analysis showed that carbamazepine significantly increased the delta-theta power and reduced the frequency of alpha rhythm; oxcarbazepine induced smaller changes than carbamazepine. Levetiracetam did not change any EEG measurements. On color visually evoked potential (VEP) tests, carbamazepine induced a constant slowing of P1 latency, while oxcarbazepine induced changes only after the blue-black pattern. All color VEP measures for volunteers receiving levetiracetam were almost unchanged.


CONCLUSIONS
After short-term treatment in healthy volunteers, carbamazepine induced major clinical and neurophysiologic changes. Oxcarbazepine was better tolerated than carbamazepine. Levetiracetam interfered least with clinical and neurophysiologic test results.
Mecarelli
Oriano
O
Department of Neurological Sciences, La Sapienza University, Rome, Italy. oriano.mecarelli@uniroma1.it
Vicenzini
Edoardo
E
Pulitano
Patrizia
P
Vanacore
Nicola
N
Romolo
Francesco Saverio
FS
Di Piero
Vittorio
V
Lenzi
Gian Luigi
GL
Accornero
Neri
N
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D002220:Carbamazepine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D000078330:Oxcarbazepine; D010889:Piracetam / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012720:Severity of Illness Index
D000927:Anticonvulsants; D002220:Carbamazepine; D000077287:Levetiracetam; D000078330:Oxcarbazepine; D010889:Piracetam