Anti-Seizure Medicine Side Effects: What a Review Found About Neuropsychiatric Problems

What was studied

This systematic review examined whether anti-seizure medicines were associated with behavioral, cognitive, mood, sleep, or psychotic problems in people with epilepsy. Researchers searched three medical databases through May 2026.

They included 18 observational studies, reported as covering 5,151,367 patients. When studies were sufficiently comparable, the researchers combined their results; otherwise, they summarized them separately.

What they found

Memory disorders were reported in 8.7% of people receiving first-generation medicines, 3.8% receiving second-generation medicines, and 6.2% receiving third-generation medicines. Depression was reported in 2.3%, 1.2%, and 3.0% of these groups, respectively.

There was no statistically significant difference in psychosis risk between first- and second-generation medicines. The comparison between second- and third-generation medicines was borderline and imprecise. Among individual medicines, topiramate had the strongest reported association with psychosis risk. In separate studies, levetiracetam was associated with higher anxiety rates and higher odds of suicidality.

Limits of the evidence

These observational findings show associations and cannot establish that the medicines caused the neuropsychiatric problems. Residual confounding may have affected the results. Studies also varied in their comparison groups and outcome definitions. Information was limited about dose, treatment duration, use of multiple medicines, and newer anti-seizure medicines, limiting the precision and generalizability of the findings. The levetiracetam findings for anxiety and suicidality each came from one study.

For families and caregivers

The review suggests that possible changes in memory, mood, behavior, sleep, or thinking should be considered when anti-seizure medicines are selected and routinely monitored. Risks may differ among medicines, but these findings do not mean that everyone taking a particular medicine will experience these problems. Families can discuss treatment benefits, possible adverse effects, and any changes noticed during treatment with clinicians.

What to watch next

Further studies that better address confounding and provide more information about dose, treatment duration, use of multiple medicines, and newer anti-seizure medicines would help clarify these risks.

Terms in this summary

anti-seizure medication (ASM)

A medicine used to prevent or reduce epileptic seizures.

neuropsychiatric adverse event

An unwanted effect involving mood, behavior, memory, thinking, sleep, or symptoms such as psychosis.

observational study

A study that records what happens without assigning treatments, so it can identify associations but generally cannot establish cause and effect.

psychosis

A condition involving loss of contact with reality, such as hallucinations or strongly held false beliefs.

risk ratio (RR)

A comparison of how often an outcome occurs in two groups; a value of 1 indicates equal risk.

odds ratio (OR)

A comparison of the odds of an outcome in two groups; a value above 1 indicates higher odds in the first group.

confidence interval

A range showing uncertainty around an estimate; a wider range generally indicates less precision.

residual confounding

Distortion that remains when differences between patient groups are not fully measured or accounted for.