Keppra (levetiracetam) most commonly causes drowsiness, fatigue, and dizziness, with about 15% of users experiencing sleepiness or weakness in clinical trials. Most people tolerate it well enough to stay on the medication, but behavioral and mood changes are a real concern, especially in children. Here’s what to expect across the full range of possible effects.
The Most Common Side Effects
In pooled clinical trials of adults with partial-onset seizures, the five most frequently reported side effects were fatigue (15%), drowsiness (15%), headache (14%), infection (13%), and dizziness (9%). For context, people taking a placebo in those same trials reported similar issues at noticeably lower rates: 9% for fatigue, 8% for drowsiness, and 4% for dizziness. The gap between Keppra and placebo tells you which effects are genuinely caused by the drug versus just being part of everyday life.
Drowsiness and fatigue tend to be most noticeable when you first start taking Keppra or after a dose increase. For many people, these effects ease up over the first few weeks as the body adjusts. Dizziness follows a similar pattern. These are the side effects most likely to affect your daily routine early on, particularly driving, concentration at work, or exercising.
Mood and Behavioral Changes
This is where Keppra stands apart from many other seizure medications. Irritability, aggression, anxiety, and depression are well-documented effects that can develop in the weeks after starting treatment. In a study of over 1,400 patients, about 7.8% developed severe psychiatric symptoms. Some patients experienced suicidal thoughts or self-harm behaviors.
These mood changes can be subtle at first. You might notice a shorter fuse, increased frustration over small things, or a sense of emotional flatness. Sometimes the people around you notice before you do. The effect is real enough that neurologists often ask patients and their families to watch for personality shifts, particularly in the first few months.
Children Are More Vulnerable
Behavioral side effects hit children harder. A systematic review of 13 studies covering 727 pediatric patients found that children on Keppra were roughly twice as likely to develop behavioral problems compared to children on placebo. Hostility, nervousness, and aggression were the most commonly reported issues. That said, the effects were severe enough to require stopping the medication in only about 2% of children in controlled trials, and some observational studies actually found behavioral improvements alongside the problems. The picture is mixed, but the risk is clearly higher than in adults.
How Dosage Affects Side Effects
Higher doses generally mean more side effects. In FDA review data, the pattern is clear: at 1,000 mg per day, about 7.5% of patients dropped out of a trial due to side effects, compared to 14.2% at 2,000 mg per day. Drowsiness, dizziness, irritability, and fatigue all appear to scale with dose. This is why most prescribers start at a lower dose and increase gradually, giving your body time to adjust at each step.
At typical doses (1,000 to 3,000 mg per day), discontinuation rates due to side effects range from about 6% to 9%, which is only slightly higher than placebo groups. That’s a meaningful sign that most people can tolerate the medication. At the highest studied dose of 4,000 mg per day, the dropout pattern was less predictable, suggesting individual variation matters more at extreme doses.
A Rare but Serious Reaction: DRESS
The FDA issued a specific warning that Keppra can trigger a rare reaction called DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). This typically appears 2 to 8 weeks after starting the medication, though it can show up earlier or later. DRESS can start as a fever or rash but may progress to damage the liver, kidneys, lungs, heart, or pancreas. It can be life-threatening if not caught early.
Warning signs to watch for include:
- Fever or sore throat
- Swollen lymph nodes
- Skin rash, facial swelling, or swelling around the eyes
- Yellowing of the skin or eyes
- Unusual bruising or bleeding
- Severe fatigue, shortness of breath, or muscle pain
- Painful sores in the mouth or around the eyes
One tricky aspect of DRESS is that a rash may not always be visible, even when the reaction is already underway internally. Fever and swollen lymph nodes alone can be early signs. This reaction is genuinely rare, but it requires immediate medical attention because it can escalate quickly.
Effects on Bone Health and Calcium
Many seizure medications are known to weaken bones over time, so this is a natural concern for long-term users. The good news is that a meta-analysis of 13 studies covering 612 patients found that Keppra does not appear to reduce bone mineral density in the spine or hip. That puts it in a better position than several older seizure drugs.
There is one caveat: Keppra was linked to a significant decrease in blood calcium levels. Other bone-related markers like vitamin D, phosphorus, and parathyroid hormone were not meaningfully affected. The calcium drop is worth monitoring over time, particularly if you’re already at risk for low calcium from other causes.
Safety During Pregnancy
For women of childbearing age, the safety profile during pregnancy is a critical factor in choosing a seizure medication. A 2023 Cochrane review found that the rate of major birth defects in babies exposed to Keppra during pregnancy ranged from 2.6% to 2.8%. That’s comparable to the 2.1% to 3.3% rate seen in women without epilepsy, and it’s on par with lamotrigine, the other seizure medication generally considered lowest-risk in pregnancy.
When researchers directly compared outcomes to women with untreated epilepsy (who face their own risks from uncontrolled seizures), Keppra did not increase the chance of malformations. This makes it one of the more reassuring options for managing seizures during pregnancy, though the data on specific types of malformations and higher doses is still limited.
What the Dropout Rates Tell You
One useful way to gauge how tolerable a medication really is: look at how many people quit taking it because of side effects. Across Keppra’s pivotal clinical trials, discontinuation rates due to adverse events ranged from about 6% to 14% depending on the dose, compared to 5% to 15% for placebo. At the most commonly prescribed doses, the gap between Keppra and placebo is small, typically just 1 to 2 percentage points.
This means the vast majority of people who start Keppra are able to continue taking it. The side effects are real and sometimes disruptive, but they’re manageable for most. The exceptions tend to be people who develop significant mood or behavioral changes, which can be serious enough to warrant switching to a different medication entirely.