Is phenytoin used for trigeminal neuralgia? Understanding its role in treatment

While carbamazepine is the standard first-line treatment for trigeminal neuralgia (TN), phenytoin has a documented history of use for nerve pain and continues to play a role, particularly in managing acute pain crises. Though its use has evolved, understanding when and how is phenytoin used for trigeminal neuralgia is vital for effective management.

Quick Summary

Phenytoin is used for trigeminal neuralgia, especially for acute exacerbations via intravenous infusion for rapid relief, and as an alternative or add-on therapy for long-term oral treatment, especially in refractory cases. It is not a first-line therapy like carbamazepine.

Key Points

• Acute Crises: Intravenous phenytoin is effective for rapid, short-term relief during severe trigeminal neuralgia attacks.

• Alternative Therapy: Oral phenytoin serves as an alternative or add-on for patients who cannot tolerate or fail to respond to first-line carbamazepine.

• Mechanism of Action: Phenytoin blocks voltage-gated sodium channels, stabilizing nerve membranes and reducing the abnormal electrical firing that causes pain.

• Side Effect Profile: Significant adverse effects like gum overgrowth, dizziness, and coordination problems are possible, especially with long-term oral use.

• Monitoring: Regular blood tests are necessary to monitor phenytoin levels due to its narrow therapeutic index and risk of toxicity.

• Not First-line for Chronic Use: Carbamazepine remains the recommended first-line oral treatment for sustained efficacy and generally better tolerability.

Phenytoin, known by brand names like Dilantin®, is a well-established anticonvulsant medication primarily used to manage epilepsy. However, its mechanism of action, which involves stabilizing nerve membranes, also makes it effective for various types of nerve-related pain, including trigeminal neuralgia (TN). Its use in TN has a long history, though its role has shifted over time due to the introduction of other medications with better tolerability. Today, phenytoin is most commonly utilized in specific circumstances, such as in acute emergency situations or for patients who have not found success with standard treatments.

The Mechanism of Action: Stabilizing Overactive Nerves

The hallmark of trigeminal neuralgia is the sudden, severe, and debilitating facial pain caused by abnormal hyperexcitability of nerve fibers. Phenytoin works by targeting these overactive nerves. Its core mechanism involves the blockade of voltage-gated sodium channels. These channels are crucial for transmitting electrical signals along nerve fibers. By blocking them, phenytoin helps to:

• Reduce the rapid, high-frequency firing of nerve cells responsible for intense pain attacks.
• Stabilize the neuronal membrane, making it less excitable.

This action is similar to that of carbamazepine, the current first-line treatment, which also acts as a sodium channel blocker. This shared mechanism is why anticonvulsants are a cornerstone of TN pharmacotherapy, as they directly address the underlying neurological dysfunction causing the pain.

Current Use of Phenytoin in Trigeminal Neuralgia

While once used more broadly, modern treatment strategies reserve phenytoin for specific roles in TN management. These include:

Acute Exacerbations and Crises

In cases of a severe, acute TN crisis where oral medications are insufficient or the patient is unable to swallow, intravenous (IV) phenytoin or its prodrug fosphenytoin is often used as a rescue treatment. A retrospective study demonstrated significant or complete pain relief in a majority of patients treated with IV phenytoin for acute TN exacerbations. This provides rapid, temporary relief, creating a window of opportunity to adjust long-term oral medication or prepare for other interventions.

Adjunctive or Alternative Therapy

For long-term management, oral phenytoin is not the first-line drug of choice due to a less favorable side effect profile and potentially lower efficacy compared to carbamazepine. However, it may be used in the following scenarios:

• Refractory Cases: When a patient's pain is not adequately controlled by first-line medications, phenytoin can be added to their existing regimen.
• Intolerance to First-line Agents: For individuals who experience intolerable side effects from first-line drugs like carbamazepine, phenytoin can be a viable alternative.

It is crucial that any use of phenytoin be carefully managed and monitored by a healthcare provider, particularly for patients with complex medical histories.

Comparison of Phenytoin and Carbamazepine

Carbamazepine is the most widely studied and recommended first-line oral medication for trigeminal neuralgia. Below is a comparison to clarify why phenytoin is typically considered a secondary option for chronic oral management.

Feature	Phenytoin	Carbamazepine
Efficacy	Effective, but generally considered less potent for chronic management than carbamazepine. Effective for acute crises via IV infusion.	Considered the most effective oral treatment for initial pain control.
Side Effects	Narrow therapeutic index and significant side effects, especially with long-term use (e.g., gum overgrowth, neurological issues, skin rashes).	Common side effects include dizziness and fatigue, but can cause more serious issues, though generally considered better tolerated than phenytoin.
Drug Interactions	Prone to numerous drug interactions.	Also has significant drug interaction potential.
Monitoring	Requires regular monitoring of blood levels and potential side effects.	Requires regular monitoring of blood levels, liver function, and blood cell counts.
Role in Therapy	Second-line or adjunctive oral therapy; primary role is often IV rescue for acute crises.	First-line oral therapy for initial pain management.

Potential Side Effects and Monitoring

Phenytoin is effective but its use requires careful consideration of its side effect profile, which can be more challenging than with some other anticonvulsants. Long-term oral use is particularly associated with certain adverse effects:

• Neurological: Dizziness, incoordination (ataxia), slurred speech, confusion, and involuntary eye movements (nystagmus) can occur, especially at higher doses.
• Gastrointestinal: Nausea and vomiting are possible side effects.
• Oral Health: Long-term use can cause an overgrowth of gum tissue, making good oral hygiene essential.
• Cosmetic: Unwanted hair growth (hirsutism) and coarsening of facial features are potential long-term side effects.
• Serious Reactions: Rare but serious reactions, including severe skin rashes like Stevens-Johnson syndrome, can occur.

Due to its narrow therapeutic index, blood levels of phenytoin need to be regularly monitored to ensure they are within the effective range and to avoid toxicity. A healthcare provider will weigh these risks against the potential benefits, especially in older patients who may be more susceptible to adverse effects.

Alternative and Adjunctive Treatments

For patients with trigeminal neuralgia, especially those who cannot tolerate or do not respond to phenytoin and carbamazepine, other medications are available. These are typically considered second-line oral options or are used in combination with first-line agents.

Other Oral Anticonvulsants

• Oxcarbazepine: Similar to carbamazepine but with fewer side effects and drug interactions. It is often a preferred alternative.
• Lamotrigine: Can be effective as an add-on therapy.
• Gabapentin and Pregabalin: Often used for neuropathic pain and can be effective, particularly in patients with TN secondary to multiple sclerosis.

Other Medications

• Baclofen: A muscle relaxant that can be used alone or combined with anticonvulsants.
• Botulinum Toxin Type A: Injections of botulinum toxin have shown efficacy in treating TN.
• Intravenous Lacosamide: An alternative to IV phenytoin for acute rescue treatment, potentially with a better tolerability profile.

Surgical Options

For patients with medication-refractory TN, several surgical procedures are available, including microvascular decompression (MVD), radiosurgery, and rhizotomy. A multidisciplinary team approach is often best for managing complex cases, considering both pharmacologic and surgical interventions.

Conclusion

In summary, is phenytoin used for trigeminal neuralgia? Yes, but its role today is highly specific, primarily as an effective intravenous rescue medication for acute pain crises and as a second-line or adjunctive oral treatment for patients who do not respond to or tolerate first-line therapies. While its efficacy in calming overactive nerves is well-documented, its side effect profile makes it a less favorable long-term oral option compared to carbamazepine and newer agents. Clinicians must weigh the benefits against the risks, ensuring patients are closely monitored for potential adverse effects, especially with chronic use. With a variety of treatment options available, the management of TN is best approached individually, tailoring the therapeutic strategy to the patient's specific needs and response to therapy. For more detailed information on treatments, consult an authoritative source like the National Health Service (NHS) in the UK.

NHS information on phenytoin for trigeminal neuralgia

References

Phenytoin relieves acute exacerbations of trigeminal neuralgia. (2024). Sage Journals. Retrieved from https://journals.sagepub.com/doi/10.1177/25158163241268880 Phenytoin: medicine for epilepsy and trigeminal neuralgia - NHS. (n.d.). nhs.uk. Retrieved from https://www.nhs.uk/medicines/phenytoin/ Trigeminal Neuralgia Crisis - Intravenous Phenytoin as Acute... (2020). pubmed.ncbi.nlm.nih.gov. Retrieved from https://pubmed.ncbi.nlm.nih.gov/32981076/ Trigeminal Neuralgia Treatment & Management. (2025). emedicine.medscape.com. Retrieved from https://emedicine.medscape.com/article/1145144-treatment About phenytoin - NHS. (n.d.). nhs.uk. Retrieved from https://www.nhs.uk/medicines/phenytoin/about-phenytoin/ Trigeminal Neuralgia Medication - Medscape Reference. (2025). emedicine.medscape.com. Retrieved from https://emedicine.medscape.com/article/1145144-medication 9 Common and Rare Phenytoin Side Effects - GoodRx. (2023). goodrx.com. Retrieved from https://www.goodrx.com/phenytoin/common-side-effects Phenytoin: MedlinePlus Drug Information. (2023). medlineplus.gov. Retrieved from https://medlineplus.gov/druginfo/meds/a682022.html Trigeminal neuralgia: a practical guide. (n.d.). pn.bmj.com. Retrieved from https://pn.bmj.com/content/21/5/392 Fosphenytoin: An Intravenous Option for the Management of Acute ... (2001). sciencedirect.com. Retrieved from https://www.sciencedirect.com/science/article/pii/S088539240100269X

Frequently Asked Questions

Is phenytoin the first-line medication for trigeminal neuralgia?

No, phenytoin is not a first-line treatment for trigeminal neuralgia. Carbamazepine is the standard first-line oral medication due to extensive evidence supporting its use for chronic management.

When is phenytoin used to treat trigeminal neuralgia?

Phenytoin is typically used for acute trigeminal neuralgia crises, often administered intravenously for rapid pain relief. It can also be used as a second-line or add-on oral therapy for patients who do not respond to or cannot tolerate carbamazepine.

How does phenytoin work to relieve nerve pain?

Phenytoin relieves nerve pain by blocking voltage-gated sodium channels on nerve cells. This action stabilizes the nerve membrane and reduces the high-frequency firing of electrical signals, which is responsible for the sharp, shooting pain of trigeminal neuralgia.

What are the common side effects of phenytoin?

Common side effects include neurological issues like dizziness, incoordination (ataxia), and slurred speech, as well as gastrointestinal problems like nausea. Long-term oral use can cause gum tissue overgrowth and unwanted hair growth.

Does phenytoin require special monitoring?

Yes, due to its narrow therapeutic index, phenytoin requires regular monitoring of blood levels. This helps ensure the drug is within a safe and effective range and prevents toxicity.

Are there other medications with fewer side effects than phenytoin?

Yes, other medications for trigeminal neuralgia, such as oxcarbazepine, are often considered alternatives because they tend to have fewer side effects and drug interactions than phenytoin. Newer drugs may also offer better tolerability.

Can IV phenytoin be used in an emergency?

Yes, intravenous (IV) phenytoin or its prodrug, fosphenytoin, is used in emergency settings to provide rapid pain relief during severe trigeminal neuralgia crises.

How is phenytoin's efficacy in trigeminal neuralgia compared to carbamazepine?

While both drugs work similarly, carbamazepine is generally considered more effective for long-term oral management and has a better safety profile for chronic use. Phenytoin is less effective for sustained relief but is valuable for acute situations.