Valproate Linked to Higher Mortality, Lamotrigine Shows Safer Profile in Dementia-Related Epilepsy: Study
Sweden: A large nationwide study from Sweden has shed new light on how the choice of antiseizure medication (ASM) may influence survival in people living with both dementia and epilepsy—an increasingly recognized and challenging clinical combination.
Published in Neurology, the research was led by Johan Zelano from the Department of Clinical Neuroscience at the University of Gothenburg. The investigators aimed to address an important gap in clinical practice: while newer ASMs are often recommended, real-world evidence comparing their long-term outcomes in patients with dementia has been limited.
To explore this, the researchers conducted a population-based cohort study using Swedish national health registers. They identified 5,764 individuals diagnosed with both dementia and epilepsy who began ASM therapy between 2006 and 2023. The study focused on the four most commonly prescribed medications—carbamazepine, levetiracetam, lamotrigine, and valproate—while also accounting for other less frequently used drugs. Patients were followed over time to assess overall survival and causes of death.
Key Findings:
- The analysis demonstrated clear differences in survival outcomes across antiseizure medications.
- Valproate use was consistently associated with a higher risk of death compared to other treatment options.
- This increased mortality risk with valproate remained significant even after adjusting for age, sex, comorbidities, and year of treatment initiation.
- Lamotrigine was linked to a significantly lower risk of death.
- Levetiracetam showed a trend toward improved survival across multiple analyses.
- The findings remained consistent across different statistical methods, including propensity score matching and alternative survival models, reinforcing their reliability.
- Differences were also observed in cause-specific mortality among treatment groups.
- Cardiovascular deaths were more common in patients treated with valproate or carbamazepine.
- Patients receiving lamotrigine and levetiracetam had comparatively lower risks of cardiovascular mortality.
- Compared to carbamazepine, valproate was associated with a higher risk of cardiovascular death.
- Lamotrigine demonstrated a protective effect against cardiovascular mortality when compared with carbamazepine.
These observations carry important implications for clinical decision-making. Dementia patients are particularly vulnerable due to age, frailty, and multiple comorbidities, making medication safety a key priority. The results support current expert recommendations that favor newer ASMs like lamotrigine and levetiracetam over older agents such as valproate in this population.
The researchers emphasized that careful selection of antiseizure therapy can potentially improve outcomes in patients with coexisting dementia and epilepsy. They also underscored the value of large-scale registry data in capturing real-world treatment effects over extended periods.
While the study provides strong evidence favoring certain medications, the authors note that further research is needed—particularly involving newer ASMs—to expand therapeutic options and refine treatment strategies. For now, the findings reinforce a critical message: in vulnerable populations like those with dementia, the choice of medication can have a meaningful impact on survival.
Reference:
Zelano J, Larsson D, Idegård A, Brigo F. Differences in Survival Associated With the First Antiseizure Medication in People With Dementia and Epilepsy. Neurology. 2026 May 12;106(9):e214929. doi: 10.1212/WNL.0000000000214929. Epub 2026 Apr 17. PMID: 41996657; PMCID: PMC13107405.
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