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Systematic review finds levetiracetam linked to psychobehavioral adverse effects in epilepsyLevetiracetam linked to irritability and aggression in epilepsy patients

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Key Takeaway
Consider psychobehavioral adverse effects when prescribing levetiracetam for epilepsy.

This is a systematic review examining psychobehavioral adverse effects (PBAEs) associated with levetiracetam use in epilepsy, including generalized and focal types. It synthesizes data on the frequency and impact of these effects, without reporting on study population, sample size, comparator, or follow-up duration.

Key findings include mean reported rates of specific PBAEs: irritability at 9.9%, anger at 2.5%, and aggressiveness at 2.6%. Discontinuation rates attributable to aggression and irritability ranged from 2.4% to 3.4%. The review notes that PBAEs are the most frequently reported adverse events, with others including neurological, dermatological, muscular, and hematological effects; serious adverse events include psychosis and suicidality.

The authors emphasize that the evidence is observational, with risk factors associated with increased likelihood but not causation. Limitations and practice relevance are not reported. Clinicians should interpret these findings cautiously, as the review does not provide pooled effect sizes, confidence intervals, or details on study design to assess certainty.

If you or a loved one takes levetiracetam for epilepsy, you may worry about mood or behavior changes. A new review looked at how often this drug is linked to psychobehavioral side effects.

The review found that irritability was reported in about 10% of patients, while anger and aggressiveness each appeared in roughly 2.5%. Discontinuation rates due to aggression and irritability ranged from 2.4% to 3.4%. The review also noted rare reports of psychosis and suicidality.

This looked at people with generalized and focal epilepsy taking levetiracetam, but the review did not report how many people were included or from what settings. The findings show an association, not proof the drug causes these effects, and risk factors may play a role.

Because the review did not include a control group or detailed study methods, we can’t compare these rates to other epilepsy drugs. Still, it highlights the importance of watching for mood or behavior changes and talking with a clinician if they appear.

What this means for you:
Levetiracetam may raise irritability and aggression in some epilepsy patients.

Study Details

Study typeSystematic review
EvidenceLevel 1
PublishedApr 2026
View Original Abstract ↓
Levetiracetam (LEV) is a broad-spectrum, second-generation anti-seizure medication and is commonly used as a first-line therapy for both generalized and focal epilepsies. A wide range of adverse effects has been reported with LEV, including neurological, dermatological, muscular, and hematological effects. However, psychobehavioral adverse effects (PBAEs) are the most frequently reported. The aim of this review is to explore different psychobehavioural adverse effect of LEV, the risk factors and specific available interventions. Serious but uncommon psychiatric adverse effects include psychosis and suicidality, whereas behavioral adverse effects, such as irritability, aggression, and agitation, are more common. The mean reported rates of irritability, anger, and aggressiveness are 9.9, 2.5, and 2.6%, respectively, with reported discontinuation rates of 2.4–3.4% attributable to aggression and irritability. Several risk factors have been associated with an increased likelihood of developing PBAEs, including a prior history of psychiatric illness, male sex, age
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