A recent case prompted me to create a blog post about tapering seizure medications. Tapering and discontinuing anti-seizure medications is a delicate process that requires close clinical monitoring and a strategic approach to achieve long-term seizure control for patients. In most situations regarding tapering seizure medications, neurology will likely be involved, but in rare cases, such as hospice, limited life expectancy, or family declining to continue to see the neurologist, I’ve been consulted on these cases. Here are a few items to consider.

Whether or not to discontinue an anti-seizure medication should be individualized to the patient and should only be considered after a discussion regarding risks vs. benefits. In particular cases, such as traumatic brain injuries, certain brain tumors, or seizures triggered by environmental or other clinical factors, patients may be placed on prophylactic medications. Once they have been seizure-free for an extended period of time (some data suggests a minimum of 2 years), stopping these medications may be appropriate to reduce pill burden and side effects. 

There isn’t robust clinical literature to support a specific tapering schedule, but any research and expert opinion that is out there seems to support a 10-25% reduction every 2-4 weeks. Tapering seizure medications from high dose to off over the period of a couple of weeks is generally inappropriate.

Here’s a list of important things to consider when deciding whether or not to stop a seizure medication:

• Duration of seizure freedom (longer seizure-free period, often ≥2–5 years, lowers recurrence risk)
• Type of epilepsy syndrome or seizure classification
• Age at seizure onset (childhood-onset epilepsies often have better remission rates)
• Presence of structural brain disease (tumor, stroke, traumatic brain injury, cortical malformation)
• Number of antiseizure medications required for seizure control (monotherapy vs polytherapy)
• Seizure frequency prior to achieving control
• Duration of epilepsy before remission occurred
• Patient safety considerations if a seizure were to recur (driving, occupational risks, injury risk)
• Adverse effects or medication burden (cognitive effects, drug interactions, bone health concerns, teratogenic risk)

I also wanted to discuss individual agents when considering whether or not to taper seizure medications and how that is typically done.

Tapering Seizure Medications – Specific Agents

Levetiracetam (Keppra)

It is recommended to discontinue Keppra slowly in order to avoid the chance of seizure relapse or causing status epilepticus, a life-threatening condition that is categorized by either a seizure that lasts longer than 5 minutes or multiple seizures in a row with no regain of consciousness in between. Decreasing by 500mg every 2-4 weeks is a good starting point for most patients. For example, if a patient is taking 1,000mg twice daily, the dose would decrease to 750mg twice daily for 2 weeks (25% reduction). However, the length of time between each taper may have to be extended based on the patient’s risk factors and response to the changes. If a situation requires a more conservative reduction, a target reduction of 250 mg per day would be a consideration.

Valproic Acid 

Valproic acid is another commonly used anti-seizure medication. Divalproex (Depakote) is a slightly different formulation of valproic acid and is often used instead due to GI side effects. It is also recommended to taper slowly off of these medications since abrupt discontinuation may cause withdrawal seizures and status epilepticus. For patients on over 1,000 mg per day, tapering over 2-6 months is usually warranted, with changes between 125-250mg every 2-3 or more weeks. Patients should be closely monitored for other withdrawal symptoms, such as tremors, insomnia, or dizziness, which may indicate a need to change the tapering schedule. 

Phenytoin 

Phenytoin is an older antiseizure medication that has fallen partially out of favor due to newer medications with better side effect profiles and treatment outcomes. However, it is still used to treat seizures in specific patients. It is important to take tapering off this medication slowly as well, with a tapering schedule over the course of 3-6 months. With many patients on dosages between 300 and 600 mg per day, a dose change of about 50mg every 2-4 weeks may be appropriate for patients. Note that phenytoin kinetics are often a common board exam nugget. Just like the other medications discussed, dose changes or length of time should be individualized to the patient. 

All antiseizure medications should be tapered and discontinued under the close supervision of a neurologist (ideally) or other relevant clinicians. Even though there is no set standard protocol for stopping these medications, making sure the patient is well informed of the risks and taking the tapering low and slow will help reduce safety concerns, side effects, and seizure relapse. 

This article was written by Kaylee Poppen, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP