Levetiracetam May Be Linked To Rare Severe Mood Changes

What was studied

This paper reviewed published case reports about serious mental health symptoms reported in people taking levetiracetam, a common seizure medicine. The authors searched MEDLINE (PubMed), the Cochrane Library, and Web of Science through June 1, 2025, and included studies with primary clinical data on mania, hypomania, or psychotic episodes associated with levetiracetam.

They found 50 cases in total: 8 with mania or hypomania and 42 with psychotic episodes. The authors also assessed the quality of each case and used a standard tool to judge how likely levetiracetam was to be the cause.

What they found

Across the 50 cases, the most commonly described symptoms were delusions, aggressiveness, and manic symptoms. About 26% of the patients had temporal lobe epilepsy, and 66% had uncontrolled seizures.

The review found that published case reports describe an association between levetiracetam use and manic or psychotic episodes, but the causality assessment suggested a low probability that levetiracetam alone was responsible. The authors noted that other possible explanations were common, including epilepsy-related factors and comorbid medical conditions, and in some cases an alternative diagnosis such as manic episode with psychotic features.

Limits of the evidence

This was a review of case reports, not a controlled study. Case reports can show that a problem happened around the same time as a medicine, but they usually cannot show that the medicine caused it.

The review included 50 published cases, and important details may have been missing in some reports. There was also no comparison group of people taking levetiracetam who did not develop these symptoms. Because of this, the study cannot tell how common these reactions are or separate the possible role of levetiracetam from epilepsy-related factors or comorbid medical conditions.

For families and caregivers

For families, this review suggests that severe mood or psychotic symptoms have been reported in some people taking levetiracetam, but the reports do not show that the medicine alone was responsible in most cases. This matters because behavior changes, confusion, paranoia, or unusually elevated mood should be taken seriously, especially when seizures are hard to control or there are other medical conditions.

The study does not mean most people on levetiracetam will have these problems. It mainly shows that when these symptoms happen, doctors may need to consider the full clinical picture rather than assume the medicine alone is responsible.

What to watch next

Stronger evidence would come from larger studies that compare people taking levetiracetam with similar people on other seizure medicines and carefully track psychiatric symptoms over time.

Terms in this summary

levetiracetam

A medicine used to help prevent seizures.

psychosis

A condition that can involve losing touch with reality, such as having false beliefs or seeing or hearing things that are not there.

mania

A period of unusually high energy or mood that can include less need for sleep, fast speech, risky behavior, or irritability.

hypomania

A milder form of mania with elevated or irritable mood and increased energy.

delusions

Strong beliefs that are not true and are not changed by clear evidence.

temporal lobe epilepsy

A type of epilepsy in which seizures start in the temporal lobe of the brain.

causality

Whether one thing actually caused another thing to happen.