Ketamine And Epilepsy: Clinical Applications And Research Insights

Seizures affect more than 50 million people globally, with the potential for these conditions to have significant impacts on daily life. Seizures can not only disrupt one’s professional career and personal relationships and well-being, but they can also create uncertainty and frustration. Anti-seizure medications traditionally used to manage epilepsy can work for many, but some individuals struggle to find treatments that provide consistent results. This is especially true in treatment-resistant cases.

Due to the need for additional therapy options, researchers have been exploring alternative medications for seizures, such as ketamine. Ketamine is a schedule III controlled substance that was originally developed as an anesthetic for surgical procedures in the 1960’s. 

Today, ketamine is widely used in operating rooms for anesthesia and for acute and chronic pain management. Its applications have also expanded into managing mental health and neurological conditions like depression and ADHD, as ketamine has demonstrated strong potential in calming the brain activity that leads to seizures.

Unlike recreational ketamine, which has a strong potential for misuse, medical-grade ketamine is administered in controlled environments such as clinics or doctor’s offices to ensure safe use. For people whose seizures don’t respond to conventional treatments, ketamine offers a promising new solution. Understanding how ketamine works and how it may complement current treatment plans could lead to more effective seizure management and improved quality of life.

Understanding Ketamine’s Mechanism of Action

Ketamine’s anticonvulsant potential lies in its interaction with the brain. Seizures occur when electrical activity in the brain becomes intense and/or unbalanced, leading to disruptions in normal function. Ketamine works by targeting certain brain receptors, in particular NMDA receptors, that contribute to triggering seizures.

NMDA receptors help regulate electrical signals in the brain. When these receptors are overactive, they can contribute to the erratic brain activity seen in seizures. Ketamine blocks these receptors, helping to stabilize brain activity and reduce excessive electrical signals. By regulating NMDA receptors and controlling brain activity, ketamine offers powerful potential to reduce both the frequency and intensity of seizures. 

The mechanism of ketamine differentiates ketamine from traditional therapies, which boost brain-inhibiting chemicals like GABA.

Ketamine targets the specific receptors that are involved in seizures, which makes this medication effective for cases that don’t respond to conventional treatments.

Clinical Evidence and Applications

Research into ketamine epilepsy and seizures continues to expand and deepen, and it is giving a great deal of hope for those who do not respond to other medications or treatments. While further studies are needed to fully understand its long-term effects and whether chronic use can have a permanent impact, ketamine’s potential for treatment-resistant seizures is continuing to gain support in the medical community.

As discussed earlier, ketamine’s ability to block NMDA receptors can help reduce seizure activity, making it a potential option for people with treatment-resistant epilepsy. Case studies show that ketamine for seizures in patients who had not responded to standard therapies can be effective.

One key area of research is the use of ketamine for status epilepticus, a life-threatening condition where seizures continue for long periods without stopping. In these cases, ketamine has been used as a last-resort therapy. The results have been promising: the rapid action of ketamine calming overactive brain activity has helped prevent severe complications in many patients.

Concerns about the safety of ketamine in seizure management have been addressed in several studies, with findings showing that this medication can be used safely when administered by a healthcare professional in a controlled setting. 

Protocols for ketamine use involve close monitoring by medical professionals to ensure its safety. Typically, ketamine is introduced only after other anticonvulsant medications have proven ineffective, making it a critical last-resort treatment in emergencies.

How is Ketamine Administered?

Ketamine can be administered through various routes, each with unique characteristics regarding onset, duration, and absorption. Each of the main methods — intravenous (IV), intranasal, oral, sublingual (including troches), and intramuscular (IM) — has different dosage standards:

1. Intravenous (IV) route: Ketamine takes effect quickly when administered directly intravenously into the bloodstream, since this treatment bypasses the digestive system. IV therapy also enables precise dosing, giving clinicians the most control over the treatment.
2. Intranasal route: Intranasal ketamine offers a relatively quick onset, albeit slower than IV infusions. This option may be ideal for those with an aversion to needles, who want a treatment that takes less time than an IV infusion, or prefer a non-invasive therapy.
3. Oral route: Oral ketamine must first be metabolized by the digestive system, leading to a lower overall absorption rate and slower onset of action. However, this option is highly convenient for ongoing home management of chronic conditions like pain or mood disorders.
4. Sublingual (including troches) route: Sublingual administration utilizes the membranes under the tongue for absorption, bypassing some of the digestive process. Troches (lozenges) slowly dissolve and are often used as part of ketamine-assisted psychotherapy programs.
5. Intramuscular (IM) route: IM injections may be used in acute emergency settings or situations lacking easy access to the patient’s veins (for IV infusions). IM injections also offer a relatively fast onset of effects.

The duration of a single treatment’s effects can vary, but may last between several days to a few weeks. In general, the most effective results come from a series of ketamine treatments, since the benefits build over time.

A healthcare provider will recommend a schedule of follow-up sessions to maintain symptom relief, based on how a patient responds to treatment.

Factors Influencing Dosage

Ketamine dosage varies widely, ranging between a microdose at or below 0.1 mg/kg, to a sub-anaesthetic dose of 0.5 mg/kg. Low doses may be beneficial for those who are sensitive to the dissociative or psychedelic effects of ketamine, while higher doses may be necessary if the patient has exhibited partial or no response, or if a faster onset of effects is needed.

High-dose ketamine sessions generally require professional supervision. A healthcare provider will monitor the patient’s heart rate, blood pressure, and respiration rate throughout the treatment, and help manage possible hallucinations or other adverse effects.

In order to determine the right dose of ketamine, doctors must consider several factors to make sure a patient receives a safe and effective amount. We examine these factors below.

The Safety Profile of Ketamine

Ketamine offers a new potential treatment option for managing seizures. However, like all treatments, there are side effects to be aware of.

Common side effects of ketamine include:

• Nausea
• Dizziness
• Confusion

These side effects are generally temporary. Long-term use may raise the possibility for dependency, in rare cases. When ketamine is administered by a professional in a medical setting, side effects can be monitored and effectively managed.

The risks of side effects or overdose is greatly increased when using ketamine recreationally because unregulated doses can cause complications. For safe and effective use, be sure to only seek ketamine treatment from a licensed medical provider.

Conclusion

Research into ketamine epilepsy and seizures continues to expand, giving new hope for individuals who have treatment-resistant epilepsy. Ongoing studies are leading to improved protocols and dosing, increased safety, and additional treatment methods in using ketamine for seizures. For example, intranasal ketamine and other non-invasive delivery systems are being explored to provide faster and more convenient relief than IV infusions.

Despite its promising potential, little is currently known about the long-term effects of ketamine use for epilepsy and seizures. Researchers aim to understand these potential effects, refine dosing strategies, and improve patient selection criteria.

As research into ketamine’s role in managing seizures expands, this drug is becoming recognized as a valuable tool outside of its role in hospitals as an anaesthetic. Ketamine’s potential to reduce the frequency and severity of seizures, particularly in severe cases, offers a new treatment avenue for patients.