There is no roadmap for test driving low-dose naltrexone (LDN),
so this article offers navigation advice to help minimize the bumpy road ahead.
If you have not heard of LDN, you can read about the trial funded by AFSA. Basically,
LDN works on the immune cells in the central nervous system (the microglia) and the side
effects are mild. All other drugs prescribed for fibromyalgia (FM) target the neurons and
cause a slew of side effects.
Success Rate
What are the odds that LDN will benefit 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% improvement
in pain, in addition to 30% improvement in either fatigue or sleep. However, 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 FM patients give similar findings.
Symptoms Treated
Aside from pain, LDN can improve cognition (reduce brain fog), sleep, mood, and fatigue.
“Fatigue is a major complaint for people with FM,” says Mackey, and it can be difficult to find anything to
alleviate this symptom. Pain specialist Michael Fishman, M.D., of Lancaster, PA, adds that LDN can also reduce
postural hypertension (lightheadedness upon standing) and burning symptoms. While not every FM patient has these
symptoms, they are tough to treat.
“When choosing patients for a prescription of LDN, I like to ensure that they have FM and not just pain in a
few areas,” says Aitcheson. “The presence of other symptoms like cognitive clouding, fatigue and
poor/unrefreshing sleep tends to shift me more towards the use of LDN.”
Must Be Compounded
LDN appears to work as well, if not better, than other drugs to treat FM. Unfortunately,
your local pharmacy will only have 50 mg tablets of naltrexone and you need a tiny dose that must be specially
made at a compounding 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.”
If working with a compounding pharmacy presents a hurdle for you or your prescribing physician,
Anne Marie McKenzie-Brown, M.D., a pain specialist at Emory University in
Atlanta, GA, offers advice on Compounding Pharmacies in the last section of this article.
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 drugs on the market, 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 FM trial and it happens to be
the average dose that patients end up taking in the long term.
According to Fishman, “If nightmares or vivid dreams are present, they seem to diminish over time
or 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 capsules are used, this
requires a new script).
If you are drug sensitive, other dosing schedules may be used. “I start patients on 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 FM trial did not notice improvements
until they were on the medication for at least a month. 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 and found that 12% 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
Most FM patients require a combination of therapies to get a handle on their symptoms,
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 FM.
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 who have used this drug to treat FM for over a decade seldom
encounter patients who develop tolerance to LDN.
Drugs that target the neurons (mostly the receptors that produce transmitters) often lead to tolerance.
This is not believed to be the case when one is trying to return the microglia to their normal resting
state, but no one knows for sure.
“Lifestyle measures (exercise, sleep, diet, etc.) as well as complimentary medications should be put in
place when the effect of LDN is good in order to strengthen people’s reserve and function,” advises Aitcheson.
If LDN stops working, it won’t be so devastating. In addition, he points out that patients may not
necessarily be experiencing a loss of LDN efficacy, but rather a flare up of FM symptoms.
LDN and Opioids
INaltrexone 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, with the goal of potentially weaning patients off opioids.
“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 such that half
the drug will be eliminated from your body in four hours. 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, your local compounding pharmacy will only offer LDN in capsule form, while a few
mail-order companies are capable of dispensing scored tablets in a few pre-defined doses.
“The price range is substantial,” says McKenzie-Brown. “When I found a pharmacy that compounded scored
tablets and confirmed with my patients that they were able to cut them in half, it substantially
reduced cost.“ She only uses one-half tablets for a short period in the beginning 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 ... but shop around because some places will charge you double. Conversely,
a 90-day supply of tablets ranges from $0.57 to $0.75/tablet. Click for details on how your doctor needs to
write the scripts for dosing up and testing LDN, as well as information on mail-order pharmacies in the
United States.
Medically reviewed and edited by Nicholas Aitcheson, M.D., and Anne Marie McKenzie-Brown, M.D.
If your physician is hesitant to prescribe LDN, Dr. Aitcheson published a wonderful review article
in 2023 on using LDN for patients with FM in the Australian Journal of General Practice (AJGP).
Print out
a copy and give it to your physician (click on “download article” underneath the title/authors to
print the formatted PDF).
