Can lamotrigine help with dementia?

October 11, 2025 •

3 min read

Alzheimer's disease accounts for 60% to 80% of dementia cases, and with no cure, researchers are exploring various medications for symptom management and potential disease modification. While best known as a treatment for epilepsy and bipolar disorder, the question of "Can lamotrigine help with dementia?" has emerged in clinical and research circles, particularly regarding its effect on behavioral issues and cognitive decline.

Quick Summary

Current research on lamotrigine for dementia shows promise in treating behavioral symptoms like agitation and aggression, along with potential neuroprotective properties observed in animal models. However, its use is off-label and requires more rigorous human studies to confirm its efficacy and safety for cognitive issues.

Key Points

Limited Human Evidence: There is currently no definitive evidence from large-scale clinical trials supporting lamotrigine as a standard treatment for dementia.
Potential for Behavioral Symptoms: Small-scale human studies suggest lamotrigine might help manage behavioral and psychological symptoms of dementia (BPSD), such as agitation and aggression.
Promising Animal Research: Animal studies indicate potential neuroprotective effects in mouse models of Alzheimer's.
Favorable Cognitive Profile (Generally): Compared to older antiepileptic drugs, lamotrigine is typically considered cognitive-sparing; however, a rare, reversible dementia-like syndrome has been reported.
Significant Risks in Elderly Patients: Important risks include a boxed warning for severe skin rash, suicidal thoughts, and an increased risk of dizziness and coordination problems, which can cause falls.
Off-Label Use: The use of lamotrigine for dementia is considered off-label, and more research is necessary to confirm its role and safety.

Understanding the Role of Lamotrigine in Neurological Disorders

Lamotrigine is an anticonvulsant and mood stabilizer primarily approved for treating epilepsy and bipolar disorder. It works by stabilizing electrical activity in the brain. Its relatively favorable cognitive side effect profile compared to older antiepileptic drugs and its glutamatergic inhibitory properties have led to interest in its potential for dementia, a condition linked to excitotoxic damage and neurodegeneration.

Neuroprotective Potential Observed in Animal Studies

Research in animal models suggests lamotrigine may offer neuroprotective benefits for Alzheimer's disease. Studies on mouse models have shown that lamotrigine treatment can reduce amyloid-β and tau protein hyperphosphorylation, decrease neuroinflammation, and improve spatial cognitive deficits. These findings indicate potential beneficial effects on Alzheimer's pathology in animals, but require further research to determine if they translate to humans.

Clinical Evidence for Behavioral and Psychological Symptoms

Human research on lamotrigine for dementia has primarily focused on managing behavioral and psychological symptoms of dementia (BPSD), such as agitation and aggression. Small studies and case series have indicated that lamotrigine may help reduce these symptoms. Limited evidence from uncontrolled trials also suggests a possible positive effect on mood symptoms. However, clinical data on cognitive improvement in humans is sparse and based on older, uncontrolled trials. Lamotrigine use for dementia is considered off-label due to the preliminary nature of current human evidence.

Potential Risks and Considerations for Lamotrigine Use in Dementia

Using lamotrigine in elderly patients with dementia requires careful consideration of potential risks, including serious side effects and drug interactions.

Key Side Effects to Monitor

Lamotrigine carries an FDA boxed warning for potentially life-threatening severe skin rashes, including Stevens-Johnson syndrome. Like other similar medications, it may also increase the risk of suicidal thoughts. While generally considered to have a favorable cognitive profile, a rare, reversible dementia-like syndrome has been reported in at least one case. More common side effects such as dizziness and unsteadiness can increase the risk of falls in elderly individuals.

Medication Interactions

Elderly patients often take multiple medications, increasing the risk of drug interactions. Other medications, particularly certain antiepileptic drugs and hormonal contraceptives, can significantly impact lamotrigine levels. For instance, concurrent use with valproate increases the risk of serious skin rashes. A thorough review of all medications is crucial before considering lamotrigine for dementia.

Comparison: Lamotrigine vs. Other Mood Stabilizers in Dementia


Feature	Lamotrigine	Gabapentin	Valproate (Divalproex)
Mechanism	Inhibits presynaptic glutamate release, stabilizes electrical activity	Modulates release of GABA and other neurotransmitters	Increases GABA concentrations
Primary Use	Epilepsy, bipolar disorder	Neuropathic pain, seizures	Epilepsy, bipolar disorder, mania
Cognitive Profile	Favorable; cognitive-sparing or potentially improving	Generally considered safe, but evidence is sparse	Often associated with cognitive side effects
Effect on BPSD	Some evidence for agitation, aggression, and mood	Limited case reports suggest possible effect on agitation	Not recommended due to lack of efficacy and increased side effects
Serious Side Effects	Severe rash (boxed warning), suicidal thoughts, aseptic meningitis	Dizziness, somnolence, unsteady gait	Cognitive impairment, sedation, weight gain, low platelets

Conclusion: The Road Ahead for Lamotrigine in Dementia

While animal studies show promising neuroprotective effects, the clinical evidence for using lamotrigine in dementia is currently limited and mostly focused on managing challenging behavioral symptoms rather than improving cognitive decline itself. The use of lamotrigine for this purpose is off-label, and its potential benefits must be carefully weighed against significant risks, especially in a vulnerable elderly population. Further, robust randomized controlled trials (RCTs) are essential to determine the true efficacy, optimal dosage, and long-term safety profile of lamotrigine for specific dementia symptoms. For now, lamotrigine remains a subject of investigation rather than a standard therapeutic option for dementia. Any consideration of this treatment should be done under the strict supervision of a healthcare provider. For more detailed information on a promising animal study, see {Link: NIH https://pmc.ncbi.nlm.nih.gov/articles/PMC9241401/}.

Frequently Asked Questions

No, lamotrigine is not currently approved by the FDA for the treatment of dementia. It is an off-label use that is still under investigation, primarily for behavioral symptoms.

In mouse models of Alzheimer's disease, lamotrigine has shown promising neuroprotective effects, including improved cognitive function and reduced levels of key dementia-related pathologies like amyloid-β plaques and tau protein hyperphosphorylation.

Evidence for lamotrigine improving cognitive function in humans with dementia is very limited. Some early, small trials reported minor improvements in areas like word recognition, but larger, more definitive studies are lacking.

Key side effects include a severe skin rash (Stevens-Johnson syndrome), dizziness, unsteadiness, headache, and drowsiness. There is also an increased risk of suicidal thoughts and, in rare cases, a serious, reversible dementia-like syndrome.

Lamotrigine works by inhibiting the release of glutamate, an excitatory neurotransmitter that can cause excitotoxic damage to neurons in conditions like dementia. This antiglutamatergic property may have a cerebroprotective effect.

Lamotrigine is not a standard treatment because there is insufficient evidence from large-scale randomized controlled trials to confirm its effectiveness and safety profile for dementia, especially for cognitive symptoms. Its potential benefits must be carefully weighed against known risks.

Elderly patients with dementia often take multiple medications, increasing the risk of drug-drug interactions. For example, using lamotrigine with valproate can significantly increase the risk of severe skin rash. A doctor must carefully review a patient's complete medication list before prescribing lamotrigine.