Epilepsy

Pathophysiology, Causes, and Triggers

Seizures are caused by abnormally high-frequency discharge of a group of neurons, which can spread to other parts of the brain. Epilepsy is generally diagnosed when someone has had more than one seizure or is highly likely to have another seizure, and affects around 1% of the population. Causes of epilepsy include inherited genetics, genetic mutations, and structural brain abnormalities or injury, but for many people there is an unknown aetiology.

Triggers for seizures do not cause epilepsy but can make a seizure more likely in some people. These triggers include flashing lights, stress, menstruation, sleep deprivation, pyrexia, and alcohol.

Types of Seizures

There are several different types of seizures:

• Tonic-clonic seizures: sudden loss of consciousness, fall to the floor, muscle stiffening followed by rhythmic jerking
• Tonic seizures: stiff muscles with typically rapid recovery
• Atonic seizures: sudden loss of muscle tone (“drop attacks”) with quick recovery
• Absence seizures: brief loss of awareness of surroundings; EEG shows regular spike-and-wave activity
• Focal seizures: only one part of the brain is affected, causing unusual feelings, sensations, or movements
• Myoclonic seizures: brief jerking of muscles

People with epilepsy may experience several different types of seizures. Furthermore, seizures can be classified as focal (partial) or generalised:

• Focal seizures: affect localised brain regions but can become generalised if they spread bilaterally. When the reticular formation is involved, this leads to unconsciousness.
• Generalised seizures: affect the whole brain, including tonic-clonic and absence seizures.
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  Fig 1: Partial (focal) and Generalised seizures

Status epilepticus is a life-threatening condition where seizure activity is prolonged (typically longer than 5 minutes) or recurrent without recovery between episodes.

Management of Epilepsy

Epilepsy is primarily treated with anticonvulsant drugs. Other treatment options include brain surgery, vagus nerve stimulation, and implementation of dietary changes such as the Ketogenic diet.

The main aim of anticonvulsants is to inhibit abnormal neuronal discharge via three main mechanisms:

1. Enhancement of Gamma-Aminobutyric Acid (GABA) Action

GABA is an inhibitory neurotransmitter that exerts postsynaptic inhibition.

• The GABA(A) receptor complex can be bound by phenobarbital, benzodiazepines, and GABA itself, leading to opening of chloride channels
• Vigabatrin is an irreversible inhibitor of GABA transaminase (the enzyme responsible for GABA breakdown), therefore increases GABA levels
• Tiagabine inhibits the neuronal GABA transporter GAT1, reducing reuptake of GABA from the synapse

2. Inhibition of Voltage-Gated Sodium Channels

This is the most common mechanism of action among anticonvulsants.

• Sodium channels carry inward membrane current necessary for the generation of an action potential.

Examples include phenytoin, carbamazepine, lamotrigine, lacosamide, and topiramate.

3. Inhibition of Calcium Channel Function

• Low-threshold T-type calcium channels are rapidly inactivating and associated with absence seizures
• Ethosuximide diminishes T-type calcium currents
• Pregabalin and gabapentin bind to the alpha-2-delta subunit of voltage-gated calcium channels

Some drugs have multiple mechanisms. For example, valproate acts on sodium channels, calcium channels, inhibits GABA transaminase, and may also act at GABA-A receptors.

Created in BioRender. Boucher, M. (2026) https://BioRender.com/lriorba

Fig 1: Mechanism of Action of Valproate via inhibition of calcium and sodium channels, and enhancement of GABA activity.

Switching Manufacturers for Anticonvulsants

Switching between different manufacturers’ anticonvulsants is common due to cost, supply issues, or patient preference, but it requires careful, individualised assessment.

Although generic medicines must meet strict bioequivalence standards, some people with epilepsy (particularly those who are highly sensitive) may experience changes in seizure control or side effects when switching between brands or generic versions.

The risk varies by medication, with some drugs best kept consistent, others requiring caution, and some generally safe to switch.

Switching is usually less concerning when anticonvulsants are prescribed for non-epilepsy conditions. Before switching, clinicians should evaluate factors such as seizure stability, previous experiences with switching, adherence, and patient preferences, using a shared decision-making approach.

Maintaining consistency is particularly important for individuals with well-controlled or unpredictable seizures, as even small changes can have significant consequences.

Additional considerations include formulation differences (especially modified-release products), excipients and medication availability. While missed doses pose a greater risk than switching products, any change should be carefully planned, with specialist advice sought when needed to minimise the risk of loss of seizure control.

The following table categorises anticonvulsants into three categories to support decision making:

References

1. Antiepileptic drugs: new advice on switching between different manufacturers’ products for a particular drug – GOV.UK
2. Epilepsy – NHS 
3. About epilepsy – Epilepsy Action