Levetiracetam: Behavioral Side Effects, Dose Adjustment, and Management of Irritability and Fatigue in Partial Seizures

Levetiracetam is a widely used second-generation antiepileptic medication for the treatment of partial seizures and generalized seizures. Its side effect profile is generally favorable; however, behavioral side effects have been reported in some patients, which may limit its use in certain cases. This article explores these side effects and provides guidance on dose adjustment in the management of epilepsy.

Behavioral Side Effects of Levetiracetam

Levetiracetam is known for its efficacy and tolerability, but it is not without side effects. Among the most notable are behavioral changes, which can include irritability, fatigue, and, in rare cases, acute aggression [1]. These effects typically emerge shortly after treatment initiation or following a dose change. One study suggests that a slower titration of levetiracetam may mitigate these effects in patients with a history of psychiatric disorders [2].

In children, neuropsychiatric effects are reported in up to 13% of cases, and it has been suggested that pyridoxine supplementation could help alleviate these effects [3]. However, a recent study found no significant differences in adults treated with pyridoxine [4].

Dosing Guidelines and Adjustment in Epilepsy

Adjusting the dose of levetiracetam is crucial for maximizing its efficacy and minimizing side effects. Generally, children metabolize and eliminate levetiracetam more rapidly than adults, necessitating higher doses relative to their body weight [5]. During pregnancy, plasma concentrations of levetiracetam can significantly decrease, indicating the need for early therapeutic monitoring and dose adjustments [6].

In the treatment of drug-resistant epilepsy, levetiracetam has been shown to be more effective than placebo in reducing seizure frequency, although its efficacy is not dose-dependent in all cases [7].

Conclusions

Levetiracetam is an effective and generally well-tolerated antiepileptic drug, but behavioral side effects may limit its use in some patients. Careful titration and dose adjustment are essential to optimize treatment and minimize adverse effects. Ongoing research and clinical monitoring are vital for improving outcomes in patients with epilepsy.

Referencias

• [1] Discontinuation of levetiracetam because of behavioral side effects: a case-control study.
• [2] Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders.
• [3] Amelioration of Levetiracetam-Induced Behavioral Side Effects by Pyridoxine. A Randomized Double Blind Controlled Study.
• [4] Pyridoxine for treatment of levetiracetam-induced behavioral adverse events: A randomized double-blind placebo-controlled trial.
• [5] Preliminary efficacy of levetiracetam in children.
• [6] Antiseizure Medication Concentrations During Pregnancy: Results From the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study.
• [7] Levetiracetam add-on for drug-resistant focal epilepsy.

Created 6/1/2025