Transient improvement after brief antiepileptic drug withdrawal in the epilepsy monitoring unit--possible relationship to AED tolerance

Epilepsia. 2010 May;51(5):811-7. doi: 10.1111/j.1528-1167.2009.02494.x. Epub 2010 Jan 7.


Purpose: A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance.

Methods: We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission.

Results: A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 +/- 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 +/- 23.8 days) than patients on polytherapy (13.9 +/- 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 +/- 36.8 days) compared to patient with no prior history of AED tolerance (14.0 +/- 16.3 days).

Discussion: SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anticonvulsants / therapeutic use*
  • Carbamazepine / analogs & derivatives
  • Carbamazepine / therapeutic use
  • Drug Administration Schedule
  • Drug Resistance
  • Drug Tolerance
  • Electroencephalography / statistics & numerical data
  • Epilepsy / diagnosis
  • Epilepsy / drug therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Lamotrigine
  • Levetiracetam
  • Male
  • Oxcarbazepine
  • Piracetam / analogs & derivatives
  • Piracetam / therapeutic use
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / diagnosis*
  • Substance Withdrawal Syndrome / etiology
  • Treatment Outcome
  • Triazines / therapeutic use


  • Anticonvulsants
  • Triazines
  • Carbamazepine
  • Levetiracetam
  • Lamotrigine
  • Oxcarbazepine
  • Piracetam