Side Effects of Levetiracetam (Keppra)
Levetiracetam commonly causes behavioral side effects including irritability, mood changes, and aggression, along with somnolence, dizziness, and fatigue as its most frequent adverse effects. 1, 2
Common Side Effects
Levetiracetam's side effect profile based on FDA labeling includes:
Neurological/Psychiatric Side Effects
- Somnolence/drowsiness (15%) - most common side effect
- Dizziness (9%)
- Depression (4%)
- Nervousness (4%)
- Behavioral abnormalities:
- Irritability (6%)
- Mood swings (5%)
- Hostility (2%)
- Emotional lability (2%)
- Agitation (6%)
- Personality disorder (8%)
- Aggression (particularly in predisposed individuals)
Other Common Side Effects
- Asthenia/fatigue (10%)
- Pharyngitis (6%)
- Rhinitis (4%)
- Anorexia (3%)
- Vertigo (3%)
- Cough (2%)
- Diplopia/double vision (2%)
Time Course of Side Effects
The most common adverse events (somnolence, asthenia, and dizziness) typically appear during the first 4 weeks of treatment 1. However, behavioral side effects can emerge beyond the initial titration period and may be the most common reason for drug discontinuation 3.
Behavioral Side Effects - A Special Concern
Behavioral effects deserve special attention as they can significantly impact quality of life and medication adherence:
- Prevalence: Estimated at 12-15% of patients 4
- Manifestations: Irritability, agitation, anger, hostility, and aggressive behavior
- Higher risk populations:
- Patients with learning disabilities
- Those with prior psychiatric history
- Patients with symptomatic generalized epilepsy 4
In severe cases, levetiracetam can cause:
- Acute behavioral changes requiring medication discontinuation 5
- Delirium (rare but documented) 6
- Psychosis (estimated 1.4% prevalence) 3
Comparison to Other Antiepileptic Drugs
Despite these side effects, levetiracetam has become the drug of first choice at many neuro-oncology centers due to its overall favorable profile compared to older antiepileptic drugs 2:
- Advantages over older agents: Phenytoin, phenobarbital, and carbamazepine are no longer recommended as first-choice agents due to their worse side effect profiles and significant drug interactions 2
- Compared to lamotrigine: Lamotrigine has good antiseizure activity but requires several weeks to reach sufficient drug levels 2
Laboratory and Organ Effects
- Minimal impact on laboratory parameters
- Slight trends toward lower white and red blood cell counts have been detected
- No organ toxicity has been documented in over 500,000 patient exposures 4
Monitoring Recommendations
- Monitor for behavioral changes, especially during the first month of therapy
- Assess for psychiatric symptoms at each follow-up visit
- Consider serum level monitoring to assess compliance and for differential diagnosis of side effects 2
- Be particularly vigilant in patients with pre-existing psychiatric conditions 3
Management of Side Effects
If significant side effects occur:
- Consider dose reduction
- If behavioral side effects are severe, discontinuation may be necessary
- Symptoms typically resolve rapidly after medication discontinuation 5, 6
The favorable pharmacokinetic profile (no significant drug interactions, linear kinetics, minimal protein binding) makes levetiracetam a good choice despite these potential side effects, but patients should be counseled about possible behavioral changes and monitored appropriately.