Minocycline is an antibiotic in the tetracycline family. It’s been used for more than 30 years to combat a wide range of infections.

More recently, researchers have demonstrated its anti-inflammatory, immune-modulating, and neuroprotective properties.

Since the late 1960s, some rheumatologists have successfully used tetracyclines for rheumatoid arthritis (RA). This includes minocycline. As new classes of drugs became available, minocycline use declined. At the same time, many controlled research studies showed that minocycline was beneficial for RA.

Minocycline isn’t specifically approved by the U.S. Food and Drug Administration (FDA) for use with RA. It’s occasionally prescribed “off-label.”

Despite its beneficial results in trials, minocycline generally isn’t used to treat RA today.

About off-label drug use

Off-label drug use means that a drug that’s been approved by the FDA for one purpose is used for a different purpose that hasn’t been approved. However, a doctor can still use the drug for that purpose. This is because the FDA regulates the testing and approval of drugs, but not how doctors use drugs to treat their patients. So your doctor can prescribe a drug however they think is best for your care. Learn more about off-label prescription drug use.

Researchers and clinical studies have suggested since the late 1930s that bacteria are involved in causing RA.

Clinical and controlled research studies of minocycline use for RA in general conclude that minocycline is beneficial and relatively safe for people with RA.

Other antibiotics studied include sulfa compounds, other tetracyclines, and rifampicin. But minocycline has been the subject of more double-blind studies and clinical trials because of its broad properties.

Early research history

In 1939, the American rheumatologist Thomas McPherson-Brown and colleagues isolated a virus-like bacterial substance from RA tissue. They called it a mycoplasma.

Later McPherson-Brown began experimental treatment of RA with antibiotics. Some people initially got worse. McPherson-Brown attributed this to the Herxheimer, or “die-off,” effect: When bacteria are attacked, they release toxins that initially cause disease symptoms to flare up. This indicates that the treatment is working.

In the longer term, patients got better. Many achieved remission after taking the antibiotic for up to three years.

Highlights of studies with minocycline

A meta-analysis in 2003 of 10 studies compared tetracycline antibiotics to conventional treatment or a placebo with RA. The study concluded that tetracycline (and especially minocycline) treatment was linked to improvement that was clinically significant.

A 1994 controlled study of minocycline with 65 participants reported that minocycline was beneficial for those with active RA. The majority of people in this study had advanced RA.

A 1995 study of 219 people with RA compared treatment with minocycline to a placebo. The researchers concluded that minocycline was effective and safe in mild to moderate cases of RA.

A 2001 study of 60 people with RA compared treatment with minocycline to hydroxychloroquine. Hydroxychloroquine is a disease-modifying antirheumatic drug (DMARD) commonly used to treat RA. The researchers stated that minocycline was more effective than DMARDs for early seropositive RA.

A four-year follow-up looked at 46 patients in a double-blind study that compared treatment with minocycline to a placebo. It also suggested minocycline was an effective treatment for RA. The people treated with minocycline had fewer remissions and required less traditional therapy. This was the case even though the course of minocycline was just three to six months.

It’s important to note that most of these studies involved the short-term use of minocycline. McPherson-Brown stressed that the course of treatment to reach remission or significant improvement might take up to three years.

The exact mechanism of minocycline as RA treatment isn’t fully understood. In addition to antimicrobial action, minocycline has anti-inflammatory properties. Specifically, minocycline has been demonstrated to:

  • affect nitric oxide synthase, which is involved in collagen degradation
  • improve interleukin-10, which inhibits pro-inflammatory cytokine in synovial tissue (connective tissue around joints)
  • suppress B and T cell function of the immune system

Minocycline may have a synergistic effect. This means it could enhance RA treatment when combined with nonsteroidal anti-inflammatory drugs or other medications.

It’s suggested in the scientific literature that the best candidates are those in the early stage of RA. But some of the research indicates that people with more advanced RA might also benefit.

The usual drug protocol in research studies is 100 milligrams (mg) twice per day.

But each individual is different, and the minocycline protocol may vary. Some people may need to start out with a lower dose and work up to 100 mg or more twice a day. Others may need to follow a pulsed system, taking minocycline three days a week or varying it with other drugs.

Like antibiotic treatment for Lyme disease, there’s no one-size-fits-all approach. Also, it may take up to three years to see results in some RA cases.

Minocycline is generally well-tolerated. The possible side effects are moderate and similar to those of other antibiotics. They include:

Minocycline, especially used long term, has been shown to improve RA symptoms and to help put people in remission. It’s not widely used today, despite its proven record.

The usual arguments given against minocycline use for RA are:

  • There aren’t enough studies.
  • Antibiotics have side effects.
  • Other drugs work better.

Some researchers and rheumatologists disagree with these arguments and point to the results of existing studies.

It’s important to be involved in planning your treatment and to research the alternatives. Discuss with your doctor which may be best for your particular situation.

If you’d like to try minocycline and your doctor discourages it, ask why. Point out the documented history of minocycline use. Talk to the doctor about the side effects of taking steroids long term compared with the relatively moderate side effects of minocycline. You may want to look for a research center that has worked with minocycline and RA.