The Relationship Between Lamotrigine and Brain Fog

In this article, we will take a close look at Lamotrigine, a medication primarily used for treating epilepsy and bipolar disorder, and its potential association with brain fog. We will explore the side effects of the drug, and the evidence whether the drug causes brain fog, or can be used in its treatment.
Jakub Hantabal

Jakub Hantabal

Postgraduate student of Precision Cancer Medicine at the University of Oxford, and a data scientist.

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The Relationship Between Lamotrigine and Brain Fog

Lamotrigine is a prescription-only anticonvulsive medication that is used to treat some forms of epilepsy and bipolar disorder. The medication is available under the brand name Lamictal and is taken orally. It is available in multiple forms, including immediate-release and long-release tablets, as well as chewables and tablets that dissolve under the tongue for rapid absorption of the drug [1].

Mechanistically, lamotrigine reduces the amount of glutamate in the neurons. Glutamate is a major excitatory neurotransmitter in the human body, with roles in memory, learning, as well as movement. Reducing glutamate therefore prevents overexcitation of neurons leading to seizures. The exact mechanism of action of lamotrigine requires further research to be fully understood.

Clinically, lamotrigine is used to treat certain types of seizures in patients with epilepsy, including partial seizures and secondary generalised tonic-clonic seizures, as well as generalised idiopathic (unknown cause) epilepsy. Additionally, it is showing promise in treating absence and atonic seizures. It can be either administered alone or in combination with other drugs. In bipolar disorder, lamotrigine decreases the number of mood swing episodes by limiting neuronal hyperexcitability, and some potential effects on monoamine oxidase, an enzyme with roles in neurotransmitter metabolism [1].

In addition to epilepsy and biopolar disorder, lamotrigine has been researched with promising results for treatment of other neurological and psychiatric conditions including migraines, neuropathic pain and resistant depression [2, 3].

What are the side effects of lamotrigine?

The safety profile of lamotrigine is very good, and the medication provides benefit to thousands of people daily. However, some patients may experience side effects, which differ from person to person.

Common side effects include dizziness, which was reported in 10% of patients in a pooled analysis of three clinical trials [4]. Headaches are also common, affecting 25% of patients in the same study. Other side effects include drowsiness or lethargy, reported in approximately 21% of cases in a lamotrigine overdose study [5]. The same study also reported instances of vomiting, nausea, ataxia (inability to move), and tachycardia (increased heart rate).

Another side effect is a skin rash, which can occur in approximately 5% of patients [6]. In some cases, this can be very serious and manifest at Stevens-Johnson syndrome, which is a serious condition that starts with flu-like symptoms with the addition of widespread skin pain, and later rashes and blisters that may peel off. This can be managed by hospitalisation, immediate withdrawal of the causative medication, and treatment with corticosteroids and/or immunomodulating drugs.

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Does lamotrigine cause brain fog?

Brain fog is a term used to describe feelings of confusion, forgetfulness, and lack of focus or mental clarity. Brain fog gained traction in medical research following the COVID-19 pandemic, where it is a common symptom of long COVID, or a post-COVID syndrome.

Anectodal evidence from online forums indicates that some patients have experienced brain fog following lamotrigine therapy. However, published scientific evidence concludes no association between lamotrigine and brain fog.

It is true that some anti-epileptic medications may cause cognitive impairment. However, a study reviewing multiple clinical trials of lamotrigine concluded that the medication did not result in any cognitive decline [7]. This was supported by other studies on multiple patient cohorts. A study on children with epilepsy found that lamotrigine did not significantly affect cognition [8]. Similarly, a study on bipolar patients found that those receiving lamotrigine had better performance on a verbal fluency task compared to those receiving other anticonvulsants [9].

However, it is important to note that while lamotrigine alone may not cause cognitive impairment or brain fog, mental status changes may be a side effect of combining lamotrigine with other medications, particularly those that impact metabolism [10].

Can lamotrigine treat brain fog?

While some studies suggest neuroprotective effects of lamotrigine, as well as indications that the drug can improve cognition, further research is required to understand its applications in treatment of cognition disorders.

A study on patients with Alzheimer's disease concluded cognitive improvement in partially alleviagting symptoms of dementia and improving cognitive function [11]. This has also been implicated in other types of dementia [12]. Further studies provided some understanding into the role of lamotrigine in reducing persistent inflammation in Alzheimer's disease, which may be one of the factors contributing to the improvement of the mice [13].

Additional neuroprotective effects were determined by animal studies on cerebral ischemia, a condition where the brain is not adequately oxygenated as a result of injury or a blood clot blocking the blood supply. The infarct (area of dead tissue as a result of ischemia) volume was reduced by 31% overall, and by 51% in the cerebral cortex [14].

Conclusion

There is no direct evidence that lamotrigine causes brain fog. However, it may act as a neuroprotective drug, and may be potentially used to alleviate brain fog and improve cognition. To fully understand this, further research is required, including trials on patients.

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Jakub Hantabal

Jakub Hantabal

Jakub is a postgraduate student of Precision Cancer Medicine at the University of Oxford, and a data scientist. His research focuses on the impact of hypoxia on genetic and proteomic changes in cancer. Jakub also consults and collaborates with multiple institutions in the United Kingdom and Slovakia supporting research groups with advanced data analysis, and he also co-founded an NGO organising educational events in data science.