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Giving LDN Your Best Shot

There is no roadmap for test driving low-dose naltrexone (LDN), so this article offers navigation advice to minimize the bumpy road ahead. If you have not heard of LDN,  check the trial funded by AFSA. Basically, LDN works to quiet the immune cells in the central nervous system (the microglia) that are magnifying your symptoms. The side effects of LDN are mild. All other drugs prescribed for fibromyalgia target the neurons and cause a slew of side effects.

Success Rate

What are the odds that LDN benefits you? Sean Mackey, M.D., Ph.D., a pain specialist at Stanford University in Palo Alto, CA, was one of the investigators on AFSA’s LDN trial. He found that three out of ten patients achieved at least a 30 percent improvement in pain. The drug produced similar benefits in fatigue and sleep, but the study included only 30 people.

Nicholas Aitcheson, M.D., a rehabilitation and pain specialist in Queensland, Australia, says, “Around 200 patients have been tried on LDN in our chronic pain clinic. Anecdotally, one-third have reaped significant positive results in pain reduction and improved function.” Reports by other pain clinics involving anywhere from ten to 70 fibromyalgia patients give similar findings.

Symptoms Treated

Aside from pain, LDN helps with cognition (reduces brain fog), sleep, mood, and fatigue. “Fatigue is a major complaint for people with fibromyalgia,” says Mackey, and it’s difficult to find anything to alleviate this symptom. Pain specialist Michael Fishman, M.D., of Lancaster, PA, adds that LDN also reduces postural hypertension (lightheadedness upon standing) and burning symptoms. While not every patient has these symptoms, they are tough to treat.

“When choosing patients for a prescription of LDN, I like to ensure that they have fibromyalgia and not just pain in a few areas,” says Aitcheson. “The presence of other symptoms like cognitive clouding, fatigue and unrefreshing sleep tends to shift me towards the use of LDN.”

Must Be Compounded

LDN appears to work as well, if not better, than other drugs to treat fibromyalgia. Unfortunately, your local pharmacy only dispenses 50 mg tablets of naltrexone. To get the tiny dose needed, you must go through a compound pharmacy. Insurance companies won’t pick up the tab, but the cost of LDN is $1/day … and possibly less.

“Some patients and physicians may be nervous when using a medication that needs to be compounded,” says Aitcheson. To ease concerns, he points out, “Naltrexone has been used safely for at least 40 years and we are prescribing it at less than one tenth of the minimal normal dose.”

Working with a compounding pharmacy sometimes presents hurdles for patients or physicians. However, Anne Marie McKenzie-Brown, M.D., a pain specialist at Emory University in Atlanta, GA, offers advice on Compounding Pharmacies in the last section.

Dosing Strategy

The most common dose of LDN is 4.5 mg/day, but the range is from 1.5 to 9 mg. Just like all medications, one dose doesn’t work for everyone. LDN is usually taken as a single dose at bedtime because if side effects occur, they won’t impact daytime function.

“I just recommend that patients start at 4.5 mg at night,” says Mackey. “I don’t think that there is anything magical about that dose.” This was the dose used in the fibromyalgia trial and it happens to be the average dose patients end up taking.

According to Fishman, “If nightmares or vivid dreams are present, they improve with taking LDN in the morning instead of the evening.” Other side effects, such as headaches, nausea and anxiety are mild and occur infrequently. However, if they persist, you can drop down to a 3 mg dose and these side effects will usually go away. 

If you are drug sensitive, other dosing schedules may be used. “I start patients at 1.5 mg/day for the first week, increase it to 3 mg/day the second week, and move patients to a stable dose of 4.5 mg/day the third week,” says Aitcheson. He prescribes 1.5 mg compounded capsules during the titration phase.

McKenzie-Brown uses a similar titration schedule, but instead of capsules, she prescribes 3 mg tablets that are scored. This form of LDN is available from a few mail-order pharmacies. “I start with 3 mg tablets and ask patients to cut them in half for one to two weeks to make sure there are no side effects. Then they go to 3 mg. If they have relief and want to stay at 3 mg, we stay at this dose. Otherwise, I have patients increase to 4.5 mg. Many stay at 3 mg.”

Be Patient

LDN is not a fast-acting treatment. Patients in the fibromyalgia trial took a month to notice improvements. Both Aitcheson and McKenzie-Brown recommend being on LDN at 4.5 mg/day for three months before giving up. In fact, McKenzie-Brown published a study on the use of LDN at her chronic pain clinic. She found that 12 percent of patients did not get pain relief until after three months.

“I ask patients to reserve judgement on LDN efficacy until the end of three months,” says McKenzie-Brown. “Many patients have told me that they would have stopped LDN, but they are glad they did not.”

Complimentary Therapies

Getting a handle on fibromyalgia requires combination of therapies, so don’t view LDN as your only option. “I usually prescribe LDN as an add-on to other medications,” says Aitcheson. He recommends magnesium and duloxetine along with LDN. “These agents act on the pain amplification pathways in the brain and spinal cord.”

McKenzie-Brown refers patients to physical therapy, aquatic therapy, and acupuncture, in addition to prescribing nonopioid medications. The point is, you don’t have to wait for LDN to work to get relief from your fibromyalgia.

Increasing the Dose

If LDN is reducing your symptoms, it’s natural to wonder if a higher dose might be better. “I take it on a case-by-case basis,” says Mackey, adding “there aren’t any guidelines to direct us in this phase.”

“For the vast majority of people,” says Aitcheson, “going above 6-8 mg per day is not likely to be worth it.” Trying a higher dose requires a new script, so talk it over with your physician at a follow-up visit.

Will LDN Stop Working?

It’s possible, but physicians seldom encounter patients who develop tolerance to LDN.

Drugs that target the neurons (mostly the receptors that produce transmitters) often lead to tolerance. Returning the microglia to their normal resting state should not cause tolerance, but no one knows for sure.

“Lifestyle measures (exercise, sleep, diet, etc.) must be put in place when the effect of LDN is good,” says Aitcheson. “This strengthens people’s reserve, so if LDN stops working, it won’t be so devastating.” He also points out that patients may not be experiencing a loss of LDN efficacy, but rather a symptom flare.

LDN and Opioids

Naltrexone blocks the action of opioids, so do you have to abstain from taking this class of meds while trying LDN? Maybe not if you are only taking an opioid on an intermittent basis during the day and you take the LDN at night.

“One of two things may happen,” says Mackey. “Patients may not notice any difference in the opioid’s effectiveness, or they may experience a reduced benefit of the opioid due to the LDN.” If you are on an opioid, Aitcheson adds, “Expect more gastrointestinal side effects for the first few weeks of LDN.”

Whether you take an opioid on bad days or are on tramadol (a weak opioid), Fishman still recommends LDN. However, his standard dosing schedule is to start at 1 mg and increase 0.5 mg per week until 4.5 mg/day is reached. If a person is on an around-the-clock opioid, very low-dose naltrexone (0.5 mg or less) may be used as the starting dose.

“In this era of the opioid epidemic where opioids were prescribed when all else failed for chronic pain,” says Fishman, “we need to consider positioning alternative strategies early on, including LDN.”

Compounding Pharmacies

LDN needs to be compounded as an immediate-release, short-acting formula. If you take LDN at bedtime, it is out of your system by morning.

Whether you use a local compounding pharmacy or a mail-order company, make sure it is PCAB accredited. This means the pharmacy meets the Pharmacy Compounding Accreditation Board standards set forth in the United States. If you live outside the US, be sure your pharmacy meets the highest standards set forth by your country.

Naltrexone is dirt cheap. The cost of LDN has to do with the labor involved in making the capsules or tablets. Typically, local compounding pharmacy only offer LDN in capsule form, while a few mail-order companies dispense scored tablets.

“The price range is substantial,” says McKenzie-Brown. “When I found a pharmacy that compounded scored tablets, it substantially reduced cost.” She uses one-half tablets during the titration phase, then she switches patients to the more economical 90-day supply.

While going through a dosing up phase minimizes concerns about side effects, there are two disadvantages: increased cost and the inconvenience of requiring a second script for the target dose (usually 4.5 mg).

If you don’t want to hassle with mail-order pharmacies (or they are not available in your country), expect to pay about $1/capsule. Shop around though, because some places will charge you double.

Getting LDN

How does your doctor write the scripts for dosing up and testing LDN? Whether you work with a local or a mail-order compounding pharmacy, the information you need to know is below.

Local Pharmacies

If your local compounding pharmacy dispenses LDN capsules at a reasonable price, use them for the first three months. If LDN provides symptom relief, you can switch to a mail-order pharmacy for the long run.

If you want to dose up, rather than start out at 4.5 mg at bedtime, you will need two scripts (get both from your doctor in the same visit). Assuming you start at 1.5 mg per day, your physician will need to write the following two scripts:

Script #1
1.5 mg capsules of immediate-release naltrexone – quantity 21
Instructions: take one capsule at bedtime for the first week, then take two capsules at bedtime for the second week.

Script #2
4.5 mg capsules of immediate-release naltrexone – quantity 90
Instructions: take one capsule at bedtime

NOTE: If you are really drug-sensitive, ask your physician to change the dosing schedule for Script #1 to two weeks and increase the quantity to 42. Just keep in mind that Script #1 is an added expense to your LDN trial period.

If you want to just give 4.5 mg per day a try, you only need the second script above. However, you may ask your doctor to write Script #1, but not fill it unless you encounter side effects that can’t be managed.

Mail-Order Pharmacies
For Scored LDN Tablets

Care First Specialty Pharmacy in Mount Laurel, NJ provides scored LDN tablets in doses ranging from 0.5 mg to 6 mg. They are approved to ship to all 50 states plus the Virgin Islands, and their prices are excellent at $0.57/tablet. However, Avrio Pharmacy of Scottsdale, AZ offers a unique product: double-scored LDN “Quad” tablets. This means that you can dose up on 4.5 mg tablets and conveniently stay with the same script for the long run. Unfortunately, Avrio is not licensed to ship to 12 states.

Care First Specialty Pharmacy
TEL: (844) 822-7379
FAX: (844) 922-7379
Standard Shipping: $3.95; Cost for 90 scored tablets:
Any strength 0.5 mg – 4.5 mg is $46.95
5 mg is $48.95
6 mg is $59.95

Anything above 6 mg must be made into capsules; expect to pay closer to $80.

Dosing up in 1.5 mg increments requires 3 mg tablets; 135 costs $67.50
Patients on around-the-clock opioids may talk to their doctor about taking the 0.5 mg strength (each half tablet is only 0.25 mg). Care First also makes available “ultra” low dose naltrexone in micro-milligrams (mcg).

Patient registration forms, as well as prescriber forms, are available on their website. Or call to set up your profile for shipping address and payment info.

Avrio Pharmacy
TEL: (480) 270-6700
FAX: (480) 270-6701
Standard Shipping: $8; Cost for 90 Quad tablets:
4.5 mg (1.125 mg segments) is $60.00
2 mg (0.5 mg segments) is $60.00
6 mg (1.5 mg segments) is $75.00

Three months at 4.5 mg/day is recommended before giving up on LDN. Many patients won’t encounter appreciable side effects at this target dose to warrant dosing up. However, if you want the safety-net of being able to drop down in dose for a few days without having to fill a second script, the 4.5 mg quad tablets may be ideal for you. Just keep in mind that Avrio does not ship to the following states: AL, AR, IA, LA, MD, MS, NJ, ND, OK, TN, VT, WV.

The following medical journal article is great for healthcare providers who are hesitant to let you try LDN:
Aitcheson N, et al. Aust J Gen Pract. 2023. Low-dose naltrexone in the treatment of fibromyalgia: A systematic review and narrative synthesis 52(4):189-195. Free Report