Doctors prescribe medications to help control seizures in people with epilepsy, but some of these drugs can affect mood and behavior as side effects. Researchers reviewed 28 different seizure medications to understand which ones are more likely to cause mood changes, irritability, or aggression. They found that some medications like levetiracetam and perampanel carry higher risks, while others like carbamazepine and oxcarbazepine are gentler on mood. The study also identified risk factors that make mood problems more likely, such as taking multiple medications at once or having a history of mental health issues. The good news is that these side effects can often be prevented or reversed by choosing the right medication and monitoring patients carefully.
The Quick Take
- What they studied: How different seizure medications affect mood, behavior, and mental health in adults with epilepsy
- Who participated: This was a review of research studies and medical records from 1990 to 2025 involving thousands of epilepsy patients across many studies—not a single new study with participants
- Key finding: Seizure medications vary greatly in their mood side effects. Some drugs like levetiracetam and perampanel cause mood problems in many patients, while others like carbamazepine and oxcarbazepine rarely do. Risk factors like taking multiple drugs at once or having previous mental health issues make problems more likely.
- What it means for you: If you take seizure medication, talk with your doctor about mood changes. Your doctor can choose medications less likely to affect your mood or switch you to a different drug if problems develop. This doesn’t mean stopping seizure treatment—it means finding the right medication for you.
The Research Details
Researchers looked at all the scientific studies published about seizure medications and mood side effects from 1990 through September 2025. They searched multiple medical databases and reviewed information from drug regulatory agencies. They collected information from randomized trials (where patients randomly get different treatments), long-term observation studies, and safety reports from patients taking these medications. The researchers then organized all 28 seizure medications into five risk categories—from very low risk to very high risk for mood problems—based on how often these side effects occurred and how serious they were.
This type of study, called a narrative review, allows researchers to combine information from many different studies to see the big picture. Instead of doing one new experiment, they’re summarizing what we already know from hundreds of previous studies and medical reports. This approach is useful for understanding patterns across many medications and identifying which ones are safest.
Understanding which seizure medications are more likely to cause mood problems helps doctors make better choices when treating patients. Some patients might already struggle with depression or anxiety, so knowing which medications could make these problems worse is crucial. By organizing medications into risk categories, doctors can choose treatments that control seizures while protecting mental health. This is especially important because mood side effects are one of the main reasons patients stop taking their seizure medications, which can lead to dangerous seizures.
This review examined decades of research from reputable medical databases and included information from drug regulatory agencies, making it comprehensive and reliable. The researchers looked at different types of studies—from carefully controlled experiments to real-world patient reports—which provides a complete picture. However, because this is a review of other studies rather than a new experiment, the quality depends on the quality of the original studies reviewed. The researchers were transparent about how they organized medications into risk categories, which helps readers understand their reasoning.
What the Results Show
The research identified major differences in how seizure medications affect mood and behavior. Levetiracetam, perampanel, felbamate, and stiripentol showed the highest risk for mood problems, with irritability and aggression being the most common complaints. These medications caused mood side effects in a significant portion of patients who took them.
On the opposite end, carbamazepine, ethosuximel, lacosamide, oxcarbazepine, phenytoin, pregabalin, and primidone showed the lowest risk for mood problems. Interestingly, some of these medications actually helped improve mood in certain patients, acting almost like mood-stabilizing treatments in addition to controlling seizures.
The researchers also discovered that certain situations make mood problems more likely to happen. Taking multiple seizure medications at the same time, increasing doses too quickly, taking higher doses, having a history of mental health problems, having intellectual disabilities, and living in difficult social situations all increased the risk of experiencing mood side effects.
The study identified the biological reasons why some medications affect mood more than others. Most mood problems came from how these drugs affected specific brain chemicals and receptors. Some medications overstimulated AMPA receptors, some affected GABA systems too broadly, some depleted folate (a B vitamin important for brain health), and some blocked NMDA receptors. Understanding these mechanisms helps doctors predict which patients might have problems and how to prevent them. The research also showed that mood side effects can often be reversed by switching to a different medication, meaning patients don’t have to choose between controlling seizures and protecting their mental health.
This review builds on decades of previous research about seizure medications and mental health. Earlier studies identified that some medications caused mood problems, but this comprehensive review is the first to systematically rank all 28 commonly used seizure medications by their risk level. Previous research suggested that certain risk factors like taking multiple medications increased problems, and this review confirms and expands on those findings. The new risk-tiering system provides a practical tool that goes beyond what was previously available, helping doctors make more informed choices.
This review depends on information from other studies, so if those studies had problems, this review’s conclusions might be affected. Some older medications have less recent research available, making it harder to assess their true risk. The review focused mainly on adults, so results might not apply to children. Different studies measured mood side effects in different ways, which made combining results challenging. Additionally, the frequency of mood problems reported in studies might not match real-world experience, since people who experience severe side effects are more likely to report them than those with mild problems. Finally, this review cannot prove that medications cause mood problems—it can only show that they’re associated with them.
The Bottom Line
If you take seizure medication, discuss mood changes with your doctor—this is important and treatable. Start with one medication (monotherapy) rather than multiple medications when possible, as this reduces mood side effects. If you have a history of depression, anxiety, or other mental health issues, ask your doctor about medications in the ‘Very Low’ or ‘Low’ risk categories. If you’re taking a medication known to deplete folate, ask about taking a folate supplement. If you experience mood changes after starting or increasing a seizure medication, tell your doctor immediately—switching to a different medication often solves the problem. These recommendations are based on strong evidence from many studies and are considered safe and effective.
Anyone taking seizure medication should be aware of potential mood side effects and monitor themselves for changes. This is especially important for people with a personal or family history of depression, anxiety, bipolar disorder, or other mental health conditions. Parents of children with epilepsy should watch for behavior changes. People with intellectual disabilities may need extra monitoring since they’re at higher risk. People living in stressful situations should be particularly vigilant. However, this doesn’t mean avoiding seizure medication—it means working closely with your doctor to find the right medication for your situation. People without seizures don’t need to worry about this information.
Mood side effects from seizure medications can appear within days to weeks of starting a new medication or increasing the dose. Some people notice changes immediately, while others develop problems gradually over weeks. The good news is that if you switch to a different medication, mood improvements often happen within 2-4 weeks as the old medication leaves your system and the new one takes effect. However, everyone is different, so talk to your doctor about what to expect based on your specific situation.
Want to Apply This Research?
- Log your mood daily using a simple 1-10 scale, and note any irritability, aggression, or anxiety. Record when you start new medications or change doses. This helps you and your doctor spot patterns and decide if a medication change is needed.
- Set a weekly reminder to check in with yourself about mood changes. If you notice new irritability or mood problems after starting seizure medication, schedule a doctor’s appointment within one week rather than waiting. Keep a simple list of mood symptoms to share with your doctor.
- Create a monthly mood trend report in your app showing average mood scores and any medication changes. Share this with your doctor at each visit. If you switch medications, track mood for at least 4 weeks to see if improvements happen. Alert your doctor immediately if mood worsens significantly.
This review summarizes research about seizure medications and mood side effects but is not medical advice. Never start, stop, or change seizure medications without talking to your doctor first—stopping seizure medication suddenly can cause dangerous seizures. If you experience mood changes while taking seizure medication, contact your healthcare provider immediately. This information is for educational purposes and should not replace professional medical evaluation and treatment. Individual responses to medications vary, and your doctor can best determine which medication is right for your specific situation.