There are few effective treatments for migraines that are manufactured today. Low dose naltrexone is currently being studied as a possible treatment for prevention of episodic migraines. A large number of people suffer from migraines which can be severely debilitating. It has been estimated that as many as 18% of women and 6% of men suffer from migraines in the U.S. In most cases the migraine is severe enough that the individual can not work or function normally. It is common for episodic migraines to become chronic when they are over-treated with medication. This is because the medication actually starts to become a trigger for the migraines. This makes it especially important to find treatments that effectively reduce migraines while avoiding the risk of becoming a trigger themselves.
Medication-overuse headache (MOH)
Patients who frequently suffer from headache disorders like migraines usually will have a medication they use to manage attacks. The overuse of this medication is common as the patient tries to reduce the symptoms of their migraine. When overused, many medications used to treat migraines actually increase the frequency of attacks. This leads to a cycle of migraines and medication overuse resulting in the condition becoming chronic. MOH is usually diagnosed if there are headaches on 15 or more days per month in a patient who suffers from a headache disorder and there is a use of an acute headache medication on more than 10-15 days per month depending on the drug (for over 3 months).
This condition has also been associated with other types of substance abuse disorders. The use of opioids and triptans are more frequently implicated in MOH than aspirin or ibuprofen. Despite the prevalence of the condition, few patients with headache disorders are aware of the potential of MOH from the use of their medications. Due to the high risk of MOH from typical migraine medications, there would be a great benefit to finding a medication that can be used regularly without the risk of increasing the frequency of headaches.
Low Dose Naltrexone
Low dose naltrexone is a lower dose of the FDA approved medication naltrexone, which is indicated for the management of opiate addiction. The FDA approved dose is 50mg or more. The lower doses used are in the range of 1.5mg to 4.5mg. While at the 50mg dose naltrexone helps individuals suffering from addiction reduce their need for a drug, at lower doses the medication has different effects. These effects include reduction in inflammation and pain. Low dose naltrexone has been studied in clinical trials for treating fibromyalgia, multiple sclerosis, Crohn’s disease, complex regional pain syndrome (CRPS), and more.
One significant benefit of LDN is that it has few side effects (or no side effects at all) for most patients. It can safely be used on a daily basis and despite its effects in managing opiate addiction it actually has no addiction potential.
Theory of Migraine Causes and LDN
The recent research on LDN for the treatment of migraines is based on a particular hypothesis that migraines are the result of the excessive production of pro-inflammatory cytokines in the trigeminal gaglion. Cytokines are a part of the immune response and are associated with inflammation, pain thresholds, and in sensitization of trigeminal nerve fiber. Abnormal stimuli of the trigeminal nerve can lead to the release of vasodilators that cause blood vessels in the brain to swell and cause a migraine due to the excessive pressure.
Naltrexone has been shown to inhibit the production of pro-inflammatory cytokines that can lead to a migraine. Low dose naltrexone antagonizes Toll-like receptor 4 (TLR4) on microglia which results in the downregulation of inflammatory cytokines. It has anti-inflammatory effects in treating multiple conditions and also causes an increase in the production of endogenous opioids.
Current Research on LDN for Migraines
There are currently two studies that are not yet published in which low dose naltrexone is used to treat migraines. The studies are not yet peer-reviewed but do show some promising results for treatment with a combination of LDN with acetaminophen. In the open-label phase of one study, “treatment with the naltrexone and acetaminophen combination (n=5) led to 8.2 fewer mean monthly migraine days (from 11.8 to 3.6), representing 69.5% improvement (p=0.03), and 100% of the patients experienced a 50% reduction in monthly migraine days.”
A great indicator of the potential success of LDN is the few adverse events that were reported. Patients treated with naltrexone 2.25mg / acetaminophen 325mg and naltrexone 2.25mg experienced the same rate of adverse events as placebo-treated patients. One of the studies found that the combination with 3.25mg naltrexone was more effective than the combination with 2.25mg for this indication. All endpoints had higher response rates with the higher dose. This may signal that a particular dosage is more useful for managing migraines. For other conditions, LDN is often titrated from a starting dose of 1.5mg up to 4.5mg (and sometimes slightly higher).
One limitation of the studies is that the treatment period was only 3 months. A study with an extended treatment will be necessary to determine if there is any effect of medication overuse headache from acetaminophen, or if LDN used on its own may be effective. LDN is almost always taken daily and is not expected to be a contributing factor in MOH. However further research is needed to better understand the effects of low dose naltrexone on the frequency and severity of migraines and other headaches.
Compounding for Migraines
Low dose naltrexone can be made by a compounding pharmacy in the dosages required for treating some chronic conditions. The only manufactured form of the drug available is in much higher dosages. A compounding pharmacy can provide accurate dosing of 1.5-4.5mg doses in the form of capsules. Another compounded treatment for migraines that is not commercially available is lidocaine 4% nasal spray.
Articles
Medication-overuse Headache – StatPearls Article
The Immune System and Headache – Practical Pain Management
The Acute Treatment of Migraine with Low-Dose Naltrexone and acetaminophen Combinations and Each Component: Findings of a Small, Randomized, Double-Blind, and Placebo-Controlled Clinical Trial – Annette Toledano, M.D., Allodynic Therapeutics, LLC