Levetiracetam and Anxiety: How the Epilepsy Drug Can Trigger Worry

Levetiracetam is a broad‑spectrum anti‑epileptic medication approved by the Food and Drug Administration (FDA) in 1999 for the treatment of partial‑onset seizures. It works by binding to the synaptic vesicle protein SV2A, which modulates neurotransmitter release and stabilizes neuronal firing.

Key Takeaways

• Levetiracetam can cause anxiety in a small but notable percentage of patients.
• Risk factors include high starting doses, rapid titration, and a personal or family history of mood disorders.
• Monitoring, dose adjustment, or adding a short‑term anxiolytic often resolves symptoms.
• Alternative AEDs such as lamotrigine or gabapentin have lower reported anxiety rates.
• Open communication with neurologists and mental‑health professionals is crucial for safe management.

What Is Levetiracetam?

Beyond its brand name Keppra, levetiracetam is classified as an anti‑epileptic drug (AED). It is prescribed for adults and children with focal seizures, generalized tonic‑clonic seizures, and myoclonic seizures. Because it does not rely heavily on hepatic metabolism, it avoids many drug‑drug interactions common with older AEDs.

How Does Levetiracetam Work?

The exact mechanism remains partially understood, but the binding to SV2A is considered the primary action. By stabilizing the release of excitatory neurotransmitters like glutamate, levetiracetam reduces the likelihood of neuronal hyper‑excitability that leads to a seizure. This unique target distinguishes it from agents that modulate sodium channels or GABA receptors.

Is Anxiety a Real Side Effect?

Clinical trials reported anxiety in 1‑3% of participants, but post‑marketing surveillance suggests a higher real‑world incidence-up to 8% in some cohorts. A 2023 retrospective study of 1,200 epilepsy patients found that those who started levetiracetam at >1,000mg/day were twice as likely to develop new‑onset anxiety compared with those titrated more slowly.

These findings are echoed in patient‑reported outcomes on epilepsy forums, where users describe a "restless mind" or "persistent worry" that began within weeks of dose escalation. While not every patient experiences this, the pattern is consistent enough to warrant routine screening.

Who Is Most Likely to Feel Anxious?

Risk factors include:

• Rapid dose increases (e.g., jumping from 500mg to 2,000mg in a few days).
• Pre‑existing mood disorders such as generalized anxiety disorder or depression.
• Family history of psychiatric conditions.
• Younger age groups, especially adolescents, who may be more sensitive to central nervous system changes.

Because levetiracetam crosses the blood‑brain barrier quickly, sudden changes in concentration can affect the limbic system, the brain region that regulates emotion.

Managing Anxiety While on Levetiracetam

Step‑by‑step approach:

1. Identify early signs. Ask the patient or caregiver about irritability, racing thoughts, or trouble sleeping within the first month of therapy.
2. Document severity. Use a brief scale like the GAD‑7 (Generalized Anxiety Disorder‑7) to quantify symptoms.
3. Consult a psychiatrist. A mental‑health specialist can determine whether the anxiety is drug‑induced or part of a broader disorder.
4. Adjust dose. Slowing the titration schedule-adding 250mg every week instead of every few days-often reduces anxiety without sacrificing seizure control.
5. Consider short‑term anxiolytics. Low‑dose buspirone or an SSRI can bridge the gap while the brain adapts.
6. Evaluate alternatives. If anxiety persists despite adjustments, switching to another AED may be advisable (see comparison table below).

Open communication between the neurologist, primary care physician, and any mental‑health provider ensures that changes are made safely and that seizure control remains the priority.

Alternative AEDs With Lower Anxiety Risk

Below is a quick snapshot of three commonly used AEDs and their reported anxiety rates based on recent meta‑analyses.

If anxiety is a major concern, clinicians often start with lamotrigine because its mood‑stabilizing properties can even improve comorbid depression. However, lamotrigine requires a slow titration over weeks to avoid skin rash, so the choice must balance urgency of seizure control against side‑effect profile.

When to Seek Professional Help

Any of the following signals merit immediate evaluation:

• Sudden increase in heart rate, chest pain, or shortness of breath accompanying anxiety.
• Thoughts of self‑harm or hopelessness.
• Seizure breakthrough after dose changes.

Contact your neurologist or a mental‑health crisis line right away. Early intervention can prevent escalation and keep both seizure frequency and anxiety under control.

Bottom Line

While levetiracetam remains a first‑line option for many types of seizures, the drug is not free of psychiatric side effects. levetiracetam anxiety is a real phenomenon that can be managed with vigilant monitoring, dose adjustments, and, when needed, a switch to an alternative AED. Patients and caregivers who notice mood changes early stand the best chance of staying seizure‑free without compromising mental well‑being.