Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

Epilepsy Behav. 2017 Jul:72:17-21. doi: 10.1016/j.yebeh.2017.04.030. Epub 2017 May 29.


Purpose: To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy.

Methods: Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed.

Results: Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009).

Conclusions: One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

Keywords: Adverse effects; Antiepileptic drugs; Depression; Epilepsy; Fatigue.

MeSH terms

  • Adult
  • Anticonvulsants / adverse effects*
  • Epilepsy / drug therapy*
  • Fatigue / chemically induced*
  • Female
  • Humans
  • Levetiracetam
  • Male
  • Middle Aged
  • Piracetam / adverse effects
  • Piracetam / analogs & derivatives*


  • Anticonvulsants
  • Levetiracetam
  • Piracetam