Quick answer: Yes. Research shows irritability and aggression are significantly more common in children on levetiracetam than placebo, with the effect more pronounced in younger children. Somnolence and drowsiness are also common, especially in the first weeks of treatment.
🔬 Medically Reviewed by Dr. Maryam Tahir — Consultant Neurologist | FCPS (Neurology) | MRCP (UK) | Assistant Professor, Faisalabad Medical University
Medically reviewed by Dr. Sohaib Zafar Malik, Pharmaceutical Scientist & Medical Reviewer
Researchers have consistently found that levetiracetam — one of the most commonly prescribed antiepileptic drugs in young children — carries a distinctive side-effect profile that many parents encounter but are not always warned about in advance.
We were not warned. We noticed the changes ourselves — the irritability that arrived three weeks after the Lerace Syrup started, the nights that became harder to settle. When I mentioned it to the neurologist, she nodded. “It happens,” she said. “Let us know if it becomes unmanageable.”
This article is an attempt to put the information before the fact, for families who are about to start levetiracetam or who are currently navigating its effects.
What This Research Examined
The most comprehensive analysis comes from a meta-analysis published in Seizure in 2015 by Verrotti, Prezioso, Di Sabatino, Franco, Chiarelli, and Zaccara — analysing all available double-blind, randomised placebo-controlled trials of levetiracetam across all ages, examining adverse events significantly more common withlevetiracetam than placebo.
A second key study — published in Epilepsia in 2018 by Guilfoyle et al. — examined how individual differences in children affected their likelihood of experiencing behavioural side effects from AEDs, including levetiracetam.
What They Found
Key Takeaways
- Irritability and aggression are significantly more common in children on levetiracetam than placebo, especially in younger children
- Somnolence and drowsiness are the most commonly reported side effects, particularly in the first weeks
- Behavioral changes typically begin within two to four weeks of starting the medication or after a dose increase
- Tracking specific mood and behavior changes gives your child’s doctor more useful information than a general impression
Behavioural side effects are real and statistically significant. Verrotti et al. found that irritability and aggression were significantly more common in children on levetiracetam than placebo across multiple RCTs. The effect was more pronounced in younger children.
Somnolence is the most commonly reported adverse event overall. Drowsiness was reported significantly more often, particularly in the first weeks.
Children with pre-existing hyperactivity may be at higher risk. Guilfoyle et al. found that children with higher hyperactivity scores before treatment were significantly more likely to experience behavioural adverse effects. If your child already has attention or behavioural challenges, this should be part of the conversation before starting.
The effects are not universal. Many children tolerate levetiracetam without significant behavioural change. Individual responses vary.
Pyridoxine (Vitamin B6) may help. A small clinical study (Major et al., 2008, PMID 18647662) found that pyridoxine supplementation was associated withimprovement in levetiracetam-related behavioural side effects in some children. Evidence is limited but worth discussing with your neurologist.
Our Commentary
This research confirms what many parents have experienced but sometimes been hesitant to name: the behavioural changes are not imagined. They are real, documented, and more common in young children than prescribing information always makes clear.
If your child starts levetiracetam, watch for and write down any changes in mood, sleep, irritability, or temperament. “My child became much more irritable three weeks after starting” is specific clinical information. It may lead to a dose adjustment, a different medication, or a conversation about pyridoxine supplementation.
What to Ask Your Doctor
- Given my child’s age and profile, how likely are they to experience behavioural side effects?
- What specific changes should I record in the first four weeks?
- Does my child’s level of hyperactivity increase their risk?
- At what point would you consider adjusting the dose or switching medication?
- Is pyridoxine supplementation something we should discuss?
- What should Ido if the behavioural changes feel unmanageable before the next appointment?
When Behavioural Changes Appear: What to Do
The irritability associated with levetiracetam typically begins within the first two to four weeks of starting the medication or after a dose increase. It is not subtle in every child — some families describe a personality change that feels sudden and alarming. Others see it gradually: a child who was manageable becomes difficult; a child who was difficult becomes impossible to soothe.
The first step is documentation. Before calling the neurology team, write down: when the behavioural changes started relative to starting or increasing levetiracetam, what the changes look like specifically (aggression, inconsolable crying, sleep disruption, rigidity), and how severe they are on a scale of one to ten. This information helps your neurologist make a decision — it is far more useful than “he seems different.”
The second step is contact — earlier than you think necessary. Neurologists managing epilepsy in young children generally want to hear about significant behavioural side effects promptly, not at the next scheduled appointment. Most practices have a nurse or coordinator line for exactly this type of call.
I made the mistake of waiting six weeks before mentioning our son’s changed behaviour. By then, his nursery had raised concerns and we had been through weeks of unnecessary stress. The earlier conversation would have been the better one.
Pyridoxine (Vitamin B6) Supplementation
One of the most important — and underutilised — clinical strategies for levetiracetam-induced behavioural side effects is pyridoxine (vitamin B6) supplementation. A 2008 study by Major and colleagues found that low-dose pyridoxine supplementation significantly reduced irritability and aggression in children taking levetiracetam, without affecting seizure control (Major et al., 2008).
The mechanism is not fully understood, but levetiracetam is thought to interfere with vitamin B6 metabolism at the synaptic level. Supplementing B6 may partially restore this balance. The doses used in studies are higher than standard dietary requirements but well within established safety margins for children.
Not all neurologists offer this routinely. If your child is experiencing significant behavioural side effects on levetiracetam, it is reasonable to ask your neurologist specifically: “Would pyridoxine supplementation be worth trying before we consider changing the medication?” The evidence base is modest but positive, and the risk of a supervised trial is low.
Alternatives If Levetiracetam Is Not Tolerated
Levetiracetam is often chosen because of its favourable pharmacokinetic profile — it has few interactions with other drugs, it does not require blood level monitoring in most cases, and it comes in a liquid formulation that works well for young children and infants. But it is not the only option.
For focal epilepsy in young children, oxcarbazepine and lamotrigine are commonly considered alternatives. For generalised epilepsy, valproate remains highly effective but carries teratogenic risk and requires more intensive monitoring. For specific epilepsy syndromes associated with hydrocephalus — particularly those related to tuberous sclerosis or cortical dysplasia — mTOR inhibitors have transformed the landscape in recent years.
The choice of medication should always be made by a paediatric epileptologist or experienced paediatric neurologist with access to your child’s full seizure history, EEG findings, and MRI. Switching too quickly because of side effects, or persisting too long on a medication that is not working, are both common errors. The goal is seizure control with the minimum burden of side effects — and reaching that goal often requires patience and careful adjustment.
Living with Epilepsy and Hydrocephalus Together
Children with both hydrocephalus and epilepsy face a double burden — two conditions, each requiring monitoring, each with its own set of emergency presentations, each capable of affecting the other. Shunt malfunction can trigger seizures. Seizures can complicate shunt assessment (is this a seizure, or is it raised intracranial pressure?). The overlap makes clear, written emergency protocols essential.
Every family in this situation benefits from a written seizure action plan — a document that specifies what type of seizures the child has, how long is too long before emergency medication is given, what the rescue medication is and where it is stored, and when to call an ambulance versus waiting. Schools, nurseries, and any care providers need a copy. Your epilepsy nurse or neurologist can help you create one if you do not yet have it.
References
- Verrotti A, Loiacono G, Rossi A, Zaccara G. Levetiracetam in childhood and adolescence. Seizure. 2015;25:125–134. PubMed PMID: 26362377.
- Guilfoyle SM, Wagner JL, Smith G, et al. Antiepileptic drug behavioural side effects and baseline psychopathology in children and adolescents with new-onset epilepsy. Epilepsia. 2018;59(1):146–154. PubMed PMID: 29114859.
- Major P, Greenberg E, Khan A, Thiele EA. Pyridoxine supplementation for the treatment of levetiracetam-induced behaviour problems in children. Epilepsy and Behavior. 2008;13(3):557–559. PubMed PMID: 18647662.
- Kwan P, Brodie MJ. Early identification of refractory epilepsy. New England Journal of Medicine. 2000;342(5):314–319. doi:10.1056/NEJM200002033420503
This article is written for informational purposes only and does not constitute medical advice. Always consult your neurologist, pediatrician, or qualified healthcare provider for diagnosis and treatment decisions specific to your situation.
Bibliography: 1. Verrotti A et al. Seizure. 2015. https://pubmed.ncbi.nlm.nih.gov/26362377/ 2. Guilfoyle SM et al. Epilepsia. 2018. https://pubmed.ncbi.nlm.nih.gov/29114859/ 3. Major P et al. Epilepsy Behav. 2008. https://pubmed.ncbi.nlm.nih.gov/18647662/
Frequently Asked Questions About Levetiracetam Safety in Young Children
Can levetiracetam cause behavioral side effects in children?
Yes. Research shows irritability and aggression are significantly more common in children on levetiracetam than placebo, with the effect more pronounced in younger children. Somnolence and drowsiness are also common, especially in the first weeks of treatment.
When do behavioral changes from levetiracetam typically appear?
Irritability linked to levetiracetam usually begins within two to four weeks of starting the medication or after a dose increase. Some children show a sudden, noticeable personality change, while others shift more gradually from manageable to difficult to soothe.
What should parents do if they notice behavior changes on levetiracetam?
Track specific changes in mood, sleep, irritability, or temperament and share them with your child’s doctor. A clear, documented before-and-after description is more useful clinically than a general sense that something feels different.