Neuropsychiatric Side Effects of Levetiracetam (KEPPRA)

Neuropsychiatric Side Effects of Levetiracetam (KEPPRA)

Levetiracetam (KEPPRA) is associated with following three neuropsychiatric adverse events:

    1. Somnolence and Fatigue,
    2. Coordination difficulties, and
    3. Behavioral abnormalities.

This post will focus on behavioral abnormalities aspect of KEPPRA’s adverse effects.



Behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.):

    • This was found in 13% of KEPPRA patients vs 6% of placebo (in Adults); 37% of KEPPRA patients vs 18% of placebo (in pediatrics).


    • Hostility/aggression, nervousness/irritability (common: 1%–10%)


    • Anger, agitation (uncommon: 0.1%–1%)


    • Hence Behavioral adverse events were more common in children/adolescents than adults


    • Onset: in first 4 weeks


    • Medication discontinuation: 1.7% of treated patients discontinued due to these events, compared to 0.2% of placebo patients.


  • Warnings and precautions: “Behavioral abnormalities including psychotic symptoms, suicidal ideation,irritability, and aggressive behavior have been observed. Monitor patients for psychiatric signs and symptoms”.



Q: What are the risk factors?

    • History of febrile convulsions


    • History of status epilepticus


  • Previous psychiatric history


Note: Previous psychiatric history is less predictive than history of febrile convulsions or status epilepticus, suggesting that past psychiatric profile may be important in predicting the features of these adverse events but not necessarily their occurrence. (2)


Q: What are the treatment options?

    • Discontinuation of Levetiracetam dose: Note that these adverse events are not related to the starting dose or titration schedule.


  • If discontinuation is not an option: Lamotrigine co-therapy have protective effect.


    1. Levetiracetam package insert;
    2. Neurology 61:704–706


Please do post your questions or comments below. 

Dr. Harvinder Singh, M.D. (Admin)

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