Anti-Epileptic Drugs (AEDs)

Anti-epileptic drugs are the most common treatment for epilepsy.  The way AED’s work is not completely understood, but is thought to be related to how they act on neurotransmitters, brain cell receptors, or in the way they change the electrical channels in the nerve cell.  By keeping these nerve cell impulses calm it is thought seizures can be controlled.  AED’s do not cure epilepsy but taken as prescribed can help in preventing seizures.  The goal of AED therapy is to have improved seizure control, or “seizure freedom” while trying to balance side effects. 

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AED’s work best when taken at the same time everyday and not skipping or missing doses.  When taken correctly, AED’s can help control seizures in 7 out of 10 people.  The best type of AED for you will depend on several factors such as age, type of seizures you have, other medical concerns or medications, and if you are thinking about having a baby.  

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Side effects are dependent on medication and dose.  Common side effects with most AED’s include:  drowsiness, dizziness, fatigue, nausea/vomiting, headache, blurred vision or double vision.  Some side effects might occur when you begin a medication and usually will pass in a few days or weeks.  Take note, however there are some medications where you may not notice side effects until you’ve been taking it for several weeks. 

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Serious adverse effects can be different for AED’s, but they all include a warning message for possible allergic reactions or significant change in mood such as worsening depression, anxiety or suicidal thoughts or aggressive behavior.  Notify your provider immediately if you notice significant mood changes, facial swelling, including tongue, lips, eyes, or if you notice a rash after starting an AED.  

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Common Types of AEDs

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Sodium Channel Blocking AEDs are among the most common of AED and as the name suggests, target sodium channels.  By blocking sodium channels from returning to their active state, repetitive firing in the brain cells is prevented and can block seizure activity or reduce spread of seizures. Medications in this class include Carbamazepine, Oxcarbazepine, Eslicarbazepine, Phenytoin, Zonisamide, Topiramate, Lamotrigine, Vimpat, and Cenobamate. Common side include dizziness, fatigue, coordination problems, double vision, blurry vision, headache, nausea/vomiting, sleepiness, unsteady walking, loss of appetite. More serious side effects include:  rash, itching, swelling of hands, face or mouth, confusion, decreased urine output, fast or irregular heartbeat, muscle pain or cramps, unusual tiredness, or stomach pain.  If you do experience any signs of a rash or an allergic reaction please seek immediate care.

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AMPA receptor antagonist AED's only medication is Perampanel and it targets over-excited neurotransmission by stopping glutamate activity at postsynaptic AMPA receptors.  Too much glutamate can be associated with seizures/recurrent seizures.  Perampanel is typically started at a low dose and increased at one or two week intervals.  Common side effects include dizziness, lightheadedness, vertigo, headache, nausea or stomach pain.  More serious side effects include significant changes in behavior, suicidal thoughts, aggressive or hostile behavior.  Notify your provider immediately if you notice any serious side effects.  

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AEDs with Potential GABA Mechanism of Action include Gabapentin and Valproate and are known to have some effect on the enzyme glutamic acid decarboxylase (GAD) which converts glutamate (excitatory neurotransmitter) into GABA (calming neurotransmitter). Valproate also blocks the neuronal sodium channel during rapid sustained repetitive firing which is thought to prevent impulses that trigger seizures. Ganaxolone, also included in this class, attaches itself specifically to GABA-A to enhance its effect.  *Ganaxolone is only used for cyclin-dependent kinase-like5 deficiency disorder.  Of these three medications, in this class, Valproate is one of the most commonly used AED’s for different seizure types.  It can interact with other medications, decreasing or increasing their effects, so it is important to notify your provider of other medications you may be taking.  Common side effects include:  nausea, vomiting, tremor, sedation, confusion or irritability, and weight gain.  Notify your doctor if you notice mood changes, rash, facial swelling, yellowing of skin or white of eyes, or abdominal pain.  Women of childbearing age should also be aware of FDA required black box warnings regarding Valproate risk of birth defects if taken during pregnancy. 

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Pyrrolidine AEDs include Levetiracetam and Brivaracetam and have a mechanism of action where it binds to the synaptic vesicle protein 2A which is then thought to decrease neurotransmitter release reducing seizure activity.  Common side effects include dizziness, headache, irritability, low energy, mood and behavior changes, or sleepiness.  Notify your doctor if you notice significant change in mood, rash, hives, facial swelling, loss of balance and coordination. 

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Barbiturate AEDs include Phenobarbital and Mysoline which act by decreasing activity of the central nervous system by increasing the effectiveness of GABA.  GABA is an inhibitory neurotransmitter which helps stop the beginning of a discharge that would start a seizure.  Common side effects include dizziness, drowsiness, headache, tiredness, loss of appetite, nausea, vomiting and anxiety.  Notify your doctor if you have significant change in mood, respiratory changes, low blood pressure, or if you have a history of depression, drug abuse or suicidal tendencies.  

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Benzodiazepine AEDs are a DEA schedule IV controlled substance and include:  Clobazam, Clonazepam, Diazepam, Lorazepam and Midazolam.  The action of this drug class targets GABA-A receptors.  Because there are different GABA receptor subtypes, AED’s in this drug class can have different effects.  Generally however GABA-A subtypes can be responsible for anticonvulsant activity.  Some drugs in this class like Clobazam and clonazepam may be used for chronic epilepsy, while the others like Diazepam, Lorazepam and Midazolam are primarily used for seizure emergencies such as recurrent seizures and are used on a short term basis.  These particular AED can be potentially addictive and are to be used carefully.  Tolerance can develop over time and dependence can increase the more you take.  Common side effects include:  drowsiness, dizziness, unsteadiness, problems with coordination, muscle or joint pain or cognitive changes.  Notify your doctor if you have slurred speech, or severe symptoms such as extreme fatigue, difficulty breathing, severe mood changes, swelling of lips, face or tongue, or rash .   

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This list includes the most commonly used medications that your provider may discuss with you.  Ideally, monotherapy is preferred, but there may be occasions where two or more AED’s might be the right treatment regimen for you.  

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