Methotrexate (MTX) has been used to treat severe and/or disabling psoriasis since the early 1960s. It is also used to treat psoriatic arthritis. MTX was used initially to treat cancer and by chance it was discovered to be effective in clearing psoriasis.

Generally, MTX is reserved for people with at least 30 percent of their skin covered with psoriasis who are not responsive to, or eligible for, conventional topical or ultraviolet light treatments (UVB and PUVA). The palm of the hand represents about one percent of the skin’s surface area.

Psoriasis is a noncontagious, chronic skin disorder. Red, swollen lesions covered with dry, silvery white scales commonly characterize the condition. These lesions, or plaques, are made up of excessive skin cells produced by the body. The cause of the skin’s accelerated growth rate is unknown.

The aim of psoriasis treatments is to slow down the excessive skin cell reproduction. Generally, topical treatments are used, but sometimes psoriasis becomes extensive or disabling and systemic treatments (taking medication internally, i.e. pills and injections) are necessary. Methotrexate is a systemic treatment that can help normalize skin cell reproduction and restore the skin to a normal appearance.

How Effective is Methotrexate for Psoriasis?

MTX works best on extensive psoriasis, erythrodermic and acute pustular psoriasis, physically disabling psoriasis of the palms and soles, psoriasis in the elderly, and severe psoriatic arthritis.

The majority of patients achieve significant or even complete clearing of their disease with MTX. The clearance or remission can last for a few weeks to a year or more after stopping therapy.

MTX can be highly effective in reducing symptoms of psoriatic arthritis and arresting joint destruction caused by certain forms of psoriatic arthritis.

Can Anyone Use MTX for Psoriasis?

There are medical conditions and histories that may disqualify some patients from using MTX:

  • women who are pregnant
  • men or women who are trying to conceive a child (conception should be avoided during and for at least 12 weeks after discontinuing MTX therapy)
  • people who have blood disorders
  • people with an active peptic ulcer
  • people with severe anemia
  • people with cirrhosis of the liver
  • people with active hepatitis
  • people with significant liver or kidney abnormalities
  • people with active infectious disease
  • people who consume alcohol (beer, wine, liquor)
  • patients who are unreliable

How Is MTX Used?

MTX can be taken either by mouth or by injection. The most common way people take MTX is by mouth, either as a pill or in a liquid form. The physician will gradually adjust the dose to the smallest amount needed to achieve clearance. This minimizes the possibility of the patient experiencing side effects. MTX is usually taken in a single dose once a week.

The physician will not increase the dose of MTX to achieve total clearing (100 percent) if a few stubborn lesions remain. Instead, another therapy will generally be added, such as UVB, cortisones, or anthralin, to clear the remaining lesions.

The physician will perform a number of tests, including kidney and liver tests, to ensure the drug is safely metabolized by the body and is not adversely affecting the liver or bone marrow.

If long-term MTX therapy is anticipated, the physician may require a needle biopsy of the liver. The biopsy may be given before or after starting the drug and at intervals while the drug is taken.

The initial liver biopsy may be postponed for several months after MTX therapy has begun. This is to avoid an unnecessary procedure in case MTX therapy is stopped for any reason in a short period of time. Reasons for stopping MTX would include lack of patient response, unacceptable side effects, or rapid response not requiring any additional drug.

How Quickly Will MTX Work?

In most psoriasis patients, improvement will begin within four to six weeks. The majority of patients have substantial clearing within two or three months of starting therapy.

In psoriatic arthritis patients, it may take up to six months for the drug to have maximum effect. Effects can include decreased inflammation and pain and improved flexibility.

How Long Do People Take MTX?

Once initial clearance is achieved, the physician will generally taper or decrease the dose of MTX. If possible the physician will stop the drug all together until the symptoms return. Some people may require a maintenance dose of MTX to sustain clearance.

Short-term Side Effects

MTX can cause varying degrees of discomfort during treatment. Some people experience no complaints. The most common short-term side effects:

  • Anemia
  • Nausea
  • Insomnia
  • Loss of appetite
  • Tiredness
  • Temporary hair loss in some patients
Other less frequent side effects can include:
  • Phototoxicity (sunburn)
  • Headaches
  • Mouth ulcers
  • Chills and fever
  • Skin rash or sores
  • Light-headedness
  • Vomiting
  • Easy bruising, bleeding
  • Stomach upset and diarrhea, sometimes with blood in the stools
  • Reduced white blood cell count which can make one more susceptible to infection

Nausea can sometimes be reduced by drinking milk or eating before taking the medication. Severe nausea may mean the dose is too high. Also, if sores appear in the mouth, the dose may be too high. Although physicians have hesitated to use folic acid with MTX in the past, recently it has been shown that folic acid at a dose of 5 milligrams per day can reverse MTX-induced nausea without interfering with the beneficial effects of the drug on psoriasis.

MTX may occasionally cause a sunburn if the patient gets too much sunlight or ultraviolet light while taking the drug. This reaction has been reported even when MTX was taken several days after ultraviolet exposure.

Long-term Side Effects

MTX’s principal long-term risk is to the liver. However, the risk is less than originally thought. A small percentage of patients, generally estimated to be 1 out of 200, will develop reversible liver scarring after a cumulative dose of 1.5 grams. The risk can increase if the patient has had a cumulative dose of MTX above 1.5 grams, (one gram equals 1,000 milligrams) or if the patient has one or more of the following risk factors:

  • drinks alcohol
  • over weight
  • takes arsenic
  • has diabetes
  • has abnormal kidney function
  • has had prior liver disease

All studies indicate that the incidence of cirrhosis of the liver is minimal with a total MTX dose below 1.5 grams. A large-scale European study confirmed that liver damage caused by MTX frequently reverses once the drug is stopped.

The risk of liver damage depends on the cumulative dose, the treatment schedule, and the rest periods from taking the drug. It can take a few years or 10 to 20 years to reach the cumulative doses that pose greater risk to the liver.

The liver biopsy is considered the only reliable test for liver damage. Follow-up liver biopsies are recommended when the cumulative methotrexate dose exceeds 1.5 grams. If significant liver fibrosis develops, therapy is usually discontinued.

Liver damage that falls short of cirrhosis will generally reverse. As a rule, a year off the therapy should be sufficient for the liver to return to normal, though the length or time it takes will depend on the severity of the damage.

Does MTX pose any risk for conception or pregnancies?

MTX can cause birth defects if taken during a pregnancy. Women should not become pregnant while on MTX. Both men and women should stop MTX at least three months prior to trying to conceive a child.

Methotrexate for psoriasis has not been reported to pose any major risk to fertility in men or women and their future pregnancies. Studies of women treated with high doses of MTX for uterine cancer showed a normal pattern of fertility and normal babies after MTX treatment. Men have conceived normal offspring while taking MTX.


If you are on MTX, you should not receive a live virus vaccines. You need to be off of MTX for 3 months before being vaccinated with a live virus. If you are scheduled for any vaccinations, be sure to let your doctor know before receiving the vaccine.

In summary

Review all drugs you are taking for other conditions with your physician, including over-the-counter remedies.

Never increase the dose of methotrexate prescribed without consulting with your physician.

Contact your physician about any side effects you experience while taking MTX.

Avoid conception while on MTX and for at least 12 weeks after stopping therapy. If you become pregnant while on MTX, inform your physician immediately.

Be careful about sunbathing or exposure to ultraviolet light while on MTX. Discuss with your physician any precautions to be taken.

Do not drink alcohol while taking MTX.

Follow your physician’s instructions precisely.