Ketamine and seizure disorders

Ketamine has been used safely in medicine for decades as an anesthetic and is increasingly recognized for treating treatment-resistant depression. More recently, researchers have begun investigating whether ketamine may also play a role in treating certain seizure disorders.

While the research is still evolving, recent reviews suggest ketamine may have therapeutic potential in some neurological conditions, particularly when conventional treatments have not been effective.

Why are researchers interested?

Seizures occur when communication between brain cells becomes excessively synchronized or overly excitatory.

Ketamine blocks N-methyl-D-aspartate (NMDA) receptors, which help regulate glutamate, one of the brain's primary excitatory neurotransmitters.

Researchers believe ketamine may help by:

reducing excessive excitatory signaling
restoring the balance between excitation and inhibition in the brain
reducing abnormal synchronized neuronal activity
decreasing neuroinflammation
protecting brain cells during prolonged seizures
influencing synaptic plasticity and neural communication

These mechanisms continue to be studied and may help explain ketamine's potential role in seizure disorders.

Ketamine and epilepsy

Earlier case reports raised questions about whether ketamine could trigger seizures. However, more recent systematic reviews suggest those concerns were based on limited evidence.

Current reviews conclude that:

there is no established contraindication to ketamine solely because someone has epilepsy
evidence suggesting ketamine provokes seizures is inconsistent
ketamine may have antiepileptic properties in some clinical settings
researchers are particularly interested in its potential for drug-resistant epilepsy

At the same time, experts emphasize that additional randomized clinical trials are needed before ketamine's role in epilepsy treatment can be fully defined.

Ketamine for refractory status epilepticus

The strongest evidence currently exists for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE).

Status epilepticus is a medical emergency in which seizures continue for an extended period or occur repeatedly without recovery between episodes.

When seizures continue despite first-line medications, the condition is called refractory status epilepticus. If seizures continue despite additional anesthetic therapies, it is considered super-refractory status epilepticus.

Multiple systematic reviews and a recent meta-analysis have evaluated intravenous ketamine in these critically ill patients.

Across these studies, researchers found:

intravenous ketamine frequently contributed to seizure cessation when added to standard treatment
approximately 64% of patients in one meta-analysis experienced seizure cessation following ketamine treatment
ketamine was generally well tolerated
treatment discontinuation due to adverse effects was uncommon
several studies suggested earlier administration may be associated with better outcomes, although current evidence cannot confirm that timing alone is responsible

Because these patients are treated in intensive care settings, ketamine is used as part of a comprehensive treatment plan rather than as a stand-alone therapy.

Functional (psychogenic non-epileptic) seizures

Researchers have also begun exploring ketamine's possible role in functional seizures, also known as psychogenic non-epileptic seizures (PNES).

Unlike epilepsy, functional seizures are not caused by abnormal electrical activity in the brain. They are considered a functional neurological disorder and often occur alongside conditions such as trauma, anxiety, depression, or other psychological factors.

One published case report described a patient with both treatment-resistant depression and functional seizures whose symptoms improved after receiving intranasal esketamine.

While encouraging, this finding comes from a single patient and cannot establish that esketamine is an effective treatment for functional seizures. Larger clinical studies are needed.

What are the limitations of the current evidence?

Although interest in ketamine continues to grow, important questions remain.

Much of the current research is based on:

retrospective studies
observational research
animal models
case reports
patients receiving intensive hospital care

Researchers continue to investigate:

which seizure disorders respond best
optimal dosing strategies
treatment timing
long-term safety
differences between ketamine formulations such as ketamine, esketamine, and arketamine

Large randomized controlled trials will be essential for answering these questions.

Bottom line

Current evidence suggests ketamine is no longer viewed simply as an anesthetic with uncertain seizure risk. Instead, researchers are increasingly investigating its potential role across several seizure-related conditions.

The strongest evidence currently supports ketamine as an adjunctive treatment for refractory and super-refractory status epilepticus in hospital settings. Research into drug-resistant epilepsy is also encouraging, while studies involving functional seizures remain in the earliest stages.

As the field continues to evolve, larger clinical trials will help clarify where ketamine may fit within future seizure treatment strategies.