Treatment of First Unprovoked (Nonfebrile) Seizure


Epilepsy:  Disorder of the brain characterized by an enduring predisposition to generate seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition. (1)

Unprovoked Seizure: Seizure as a transient occurrence of signs and or symptoms as a result of abnormal excessive or enhanced synchronous neuronal activity in the brain that cannot be associated with a precipitating factor.  (1)

Types of Seizures:

  • Partial, Tonic-Clonic, Clonic, Status Epileptics-seizures lasting longer than 30 minutes
  • Seizures that were excluded were one’s associated with epilepsy which could not be diagnosed after one seizure, neonatal seizures, and seizures that were caused by an obvious cause such as CNS trauma, CNS insult, or infection


Incidence of seizures: 

  • 10% of the population will have had at least one seizure in their lifetime.
  • 25,000-40,000 children in the US will experience an unprovoked seizure a year

Risk of recurrence:

  • Current research is highly variable and is dependent on age of occurrence
  • The younger the appearance of the first seizure, the higher the risk
  • All studies performed have level 3 evidence and range from 15%-46%
  • Recurrence of multiple seizures are also highly variable
    • Incidence is higher in children with prior insult such as Cerebral Palsy or Intellectual Disability
    • Incidence also higher with patients who had abnormal EEG pattern


Common Drugs and Side Effects

There is level 2 evidence that use of AED’s have serious side effects including serious cognitive, behavioral, and system side effects. The worst of these is phenobarbital where rates of systemic side-effects range anywhere from 4%-58%!!!!!

  • Phenobarbital- behavioral changes, drowsy feeling, disturbed auditory info processing, declining cognitive performance, hyperactivity which is very common
  • Carbamazepine- Nausea/Vomiting, ataxia, headache, rash, gingival hyperplasia, impaired recent recall, severe behavior changes
  • Valproic acid- Somnolence, ataxia, rash, wt. gain, alopecia, hyperactivity
  • Phenytoin (associated with the most side effects)- gingival hyperplasia, ataxia, rash, blood dyscrasia, impaired information processing early in infancy, mood problems

Is treatment after first seizure effective for short-term prognosis?

  • Very little strong evidence in the pediatric population
  • Only one RCT shows reduced risk after 1-yr follow up of recurrence after treatment with Carbamazepine (14% vs. 53%).
  • One RCT tested Valproic Acid in both adults and pediatric patients, showing 4% risk of recurrence vs. 46%. However, another study with similar design showed no difference.

Is treatment after first seizure effective for long-term prognosis?

  • Currently 2 level 2 studies show that there is no long term benefit of starting treatment after first seizure vs. after second seizure in achieving a 1-2 year remission of seizure activity


Overall there is some weak evidence that treatment with AED after a first unprovoked seizure reduces seizure activity short term. There is stronger evidence that treatment after first seizure does not improve long term prognosis and remission rates of seizure activity compared to treatment after 2nd unprovoked seizure.

Current recommendations:

  1. First unprovoked seizure should NOT be routinely treated with AED; instead, risks of recurrent seizures and their sequelae should be weighed against possible side effects of chronic AED use.
  2. AED use does NOT prevent epilepsy, as shown by no difference in long-term outcomes in treatment and no treatment groups.


  1. Hirtz D. et al. Practice parameter: Treatment of the child with a first unprovoked seizure. Neurology January 2003
  2. Fisher R.S. van Emde Boas W. Blume W. et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005
  3. French J.A. and Pedley T.A. Initial Managment of Epilepsy NEJM 2008
  4. Berg A.T. Risk of recurrence after a first unprovoked seizure. Epi- lepsia 2008
  5. Hout S.R. et al.  Considerations in the Treatment of a First Unprovoked Seizure.  Seminars in Neurology 2008