Positive and negative psychotropic effects of levetiracetam

The goals of this study were to observe behavioral changes in patients receiving levetiracetam (LEV), a newer antiepileptic drug (AED), and to answer the question of whether LEV exerts a specific effect on impulse control and aggression.

We asked 288 consecutive patients with epilepsy on LEV (90% polytherapy, mean dose=2689 mg) and 135 relatives whether LEV caused a positive or negative behavioral change. Forty-three patients on other AEDs served as a control group. Ratings were related to patient characteristics, efficacy, dose, drug load, bidirectional ratings of change in behavioral domains, and questionnaires on personality (Fragebogens zur Persönlichkeit bei zerebralen Erkrankungen) and impulsivity (Barratt Impulsiveness Scale-11).

LEV was rated as very effective by 40% of the patients. In contrast to only 9% of the controls, a considerable number of patients reported a behavioral change while taking LEV (12% very negative, 25% negative, 16% positive, 6% very positive). Negative ratings were due to loss of self-control, restlessness, sleep problems, and, most importantly, aggression. Positive ratings were due to increased energy, vigilance, and activation. Increases in psychomotor speed, concentration, and remote memory indicated subjectively experienced positive effects on cognition. The proxy reports indicated reliable self-reports. Reported change was not related to type of epilepsy, co-therapy, dose, drug load, or psychiatric history. Negative effects were, however, associated with poorer seizure control, mental retardation, indicators of an organic psychosyndrome, and nonplanning impulsiveness.

The results indicate that LEV exerts a dose-independent stimulating effect that can be positive or negative. Aggression is a prominent feature. Lack of efficacy, mental retardation, and presumably also pre-intake disposition (organic psychosyndrome, impulsivity) may be helpful in predicting whether additional activation under LEV will be positive or negative.