Navigating temporal lobe epilepsy can be a challenge. With over 20 anti-epileptic drugs licensed in the UK, the drug options may seem overwhelming. This article provides a guide to first-line and alternative anti-epileptic drugs that are used to treat temporal lobe epilepsy, explaining how they work, their potential side effects and when other treatments may be needed. Additionally, we will explore options for drug-resistant temporal lobe epilepsy like surgical interventions and dietary changes. Read on to gain a clear understanding of the pharmacological strategies for managing temporal lobe epilepsy. 

Introduction

Around 60% of those with focal epilepsy have temporal lobe epilepsy, making it the most common type of focal epilepsy. Unfortunately, temporal lobe epilepsy is often drug-resistant, with around 70% of individuals facing drug resistance to two or more anti-seizure drugs.¹ Therefore, it is crucial to understand the pharmacological treatment options, as well as alternatives, when researching ways to manage this condition.  

Temporal lobe epilepsy originates in the temporal lobes. These lobes are located behind the ears and are responsible for things like processing auditory information, emotions and language understanding, and learning. Seizures in temporal lobe epilepsy may look like:

1. Focal aware seizures - Auras that are considered the first sign of a seizure, which include symptoms like:
   • Deja-vu
   • Strong feelings of anxiety
   • Sudden stomach upset
   • Unusual smell
   • Nausea 
2. Focal impaired awareness seizures - Seizures in which the person is conscious but may be unaware of their surroundings. These may present as:
   • Prolonged fixed staring 
   • Being unaware or confused
   • Unusual arm movement
   • Losing the ability to speak as usual
3. Tonic-clonic seizures - These are seizures that are usually associated with epilepsy that involves the whole body jerking and a loss of consciousness. 
4. Depending on where the epilepsy originates in the brain, some may experience auditory auras in which they may hear specific sounds like buzzing. 

Untreated temporal lobe epilepsy can have a severe impact on quality of life. This is why a lot of people with epilepsy tend to seek out pharmacological treatments to control seizures. Pharmaceuticals remain the first line of treatment. 

Mechanism of temporal lobe epilepsy and drug action

In epilepsy, neurons in the brain are overly-excitable. Usually, signalling in the brain is finely controlled by various ions and signalling molecules. In epilepsy, there is a structural or functional change to the brain that causes it to lose control over the firing of neurons. When different points of the brain are affected, different seizures are observed. In temporal lobe epilepsy, as the name suggests, the origin point of the epilepsy is in the temporal lobe. 

Temporal lobe epilepsy can have many causes. These include:²

1. Brain injury - caused by, for example:
   • Trauma to the head
   • Meningitis or encephalitis in early life
   • Birth injury 
2. Brain malformations
3. Brain tumours
4. Brain lesions - for example, mesial temporal sclerosis
5. Genetics

Anti-seizure medications work to decrease the excitability of neurons, hence control the frequency and severity of seizures. This can be done in a couple of different ways:

• Directly decreasing the excitability of neurons by decreasing neuronal activity
• Increasing the inhibition or control of the neurons

These mechanisms act by either:

• Altering the function of ion channels in neurons: this approach alters the way a signal is passed on within a neuron 
• Altering the release of neurotransmitters: this approach alters the way neurons communicate with each other

First-line pharmacological treatment

The pharmacological treatment of epilepsy depends on the type of epilepsy. Focal epilepsies (epilepsies that arise from a specific part of the brain) tend to have a few different first-line pharmacological treatments, which will be outlined below.³ These drugs may be used alone or in combination with other drugs or therapies. 

Carbamazepine

Carbamazepine is thought to act by inhibiting sodium ion channels thus decreasing the signalling in the neurons.⁴ This is a typical first-line therapy for focal epilepsies, hence may be the first drug that a clinician tries. However, carbamazepine may not work in up to 30% of epileptic patients, due to genetic variation affecting its breakdown in the body. 

Side effects of carbamazepine include:

• Fatigue and drowsiness
• Nausea and vomiting 
• Headache
• Dry mouth
• Weight gain
• Skin rashes 
• In the long term, carbamazepine can cause your bones to become weaker

Oxcarbazepine

Oxcarbazepine was developed from carbamazepine and shares a similar mechanism of action, but with fewer side effects. It is thought that oxcarbazepine also acts on certain calcium ion channels and is excreted differently to carbamazepine, meaning it has more potential to be used in combination with other anti-epileptic drugs.⁵ 

Side effects of oxcarbazepine include:

• Nausea, vomiting, or general stomach upset
• Dizziness and drowsiness
• Headache
• Mood changes - For example, feeling depressed or confused 
• Weight gain 

Lamotrigine

Lamotrigine acts by inhibiting sodium ion channels, which slows or stops the release of neurotransmitters - the molecules responsible for communication between neurons. Lamotrigine is also used in the treatment of type 1 bipolar disorder, hence may be a good option for epilepsy patients with mood disorders.⁶ 

Side effects of lamotrigine include:

• Headache
• Fatigue and drowsiness
• Increased aggression, irritability, or agitation
• Tremors
• Difficulties in sleeping
• Nausea, vomiting, or diarrhoea
• Skin rash
• In the long term, lamotrigine can cause your bones to become weaker

Levetiracetam

The mechanism of action of levetiracetam is still unclear, however, scientists theorise that it plays a role in inhibiting the way that neurotransmitters are released from a neuron. This decreases overall excitability, leading to less frequent or less severe seizures. Levetiracetam can be used in combination with other anti-epileptic drugs, hence it may be used as an add-on treatment.⁷ 

Side effects of levetiracetam include:

• Blocked nose or itchy throat
• Fatigue and drowsiness
• Headache
• Increased aggression, irritability or agitation
• Nausea and vomiting

Alternative and adjunctive medications

Alternative or adjunctive (add-on) medications can help to improve outcomes of first-line pharmacological therapies. Examples of different anti-epileptic drugs include:

• Lacosamide - Stabilises the hyperexcitability of neurons by modulating the way sodium channels work
• Topiramate - Blocks sodium channels and enhances the activity of neurons that inhibit other neurons
• Zonisamide - Has multiple mechanisms, including modulating the function of sodium and calcium ion channels and the making, release, and breaking-down of neurotransmitter molecules
• Clobazam - It is thought that clobazam increases the function of inhibitory neurons

Drug-resistant temporal lobe epilepsy

Depending on factors like genetics, some people with temporal lobe epilepsy may be resistant to pharmacological treatments. Drug-resistant epilepsy is defined as a person not responding to two or more anti-epileptic drugs. It is estimated that 1 in 4 people with epilepsy have drug-resistant epilepsy, with it being even more prevalent in focal epilepsies like temporal lobe epilepsy.⁹ Drug-resistant epilepsies can be detrimental, as it can lead to complications such as:¹⁰

• Increased risk of death - For example, due to sudden unexpected death in epilepsy (SUDEP)
• Decreased quality of life - Drug-resistant epilepsy can prevent an individual from pursuing their vocational interests and developing essential interpersonal skills
• Development of mental health conditions like depression
• Development of neurological impairments like memory loss

Management options for those with drug-resistant epilepsy 

There are alternative approaches for those with drug-resistant epilepsy. These include:^10,11

• Surgery
• Medication changes - Either trying out a new one or a combination of anti-epileptic drugs
• Diet changes - For example, introducing a ketogenic diet

Considerations in pharmacological treatment

When starting or changing any drug treatment, it is important to consult with a specialist in the field. This is because there are many different things to consider when starting a new medicine, for example:

• Side effects
• Genetics
• Drug-drug interactions
• Long-term monitoring

Summary 

Temporal lobe epilepsy is the most common form of epilepsy, and while it can be challenging to treat, pharmacological treatments can aid in managing seizures effectively. First-line anti-epileptic drugs like carbamazepine, oxcarbazepine, lamotrigine, and levetiracetam help to decrease the frequency or severity of seizures, by modulating neurons to be less responsive. This stabilises neuronal activity and reduces the excessive excitability of neurons in the brain that is responsible for seizures. Some individuals may experience drug-resistant epilepsy, in which they do not respond to two or more medications. In these circumstances, professionals may suggest changing medications or introducing drug combinations with medications like lacosamide, topiramate, and clobazam. Alternative routes for drug-resistant epilepsy include surgery or dietary changes. Pharmacological treatments for epilepsy are highly individualised, hence, working closely with a specialist ensures the best possible approach.