A review of Methotrexate as used in the treatment of psoriasis.

Methotrexate (MTX, also known as Trexall or Rheumatrex) is a folate antagonist (it interferes with the normal processing of folic acid) which, simply, causes a reduction in cell reproductive abilities. MTX effects cells which divide quickly (psoriatic cells, for instance) more than it does other cells. It is commonly used to stop the progression of psoriatic arthritis (and other arthritides), and less-commonly used in the treatment of severe psoriasis with no arthritic component (actually, it is probably most commonly used at higher doses as a cancer treatment).

MTX treatment typically begins with low dosages (5 to 7.5 milligrams per week). Dosage will be increased slowly (perhaps as slowly as 2.5 mg per month) until acceptable results are seen. Dosages above 30 mg per week are extremely rare in psoriasis and psoriatic arthritis. If used for psoriasis alone, the use of MTX will generally only continue until the skin symptoms are reduced to the point where other, more common, treatments may be used (such as steroids or coaltar).

In most cases, MTX will be prescribed in pill form, but MTX is also available as an injection, which may allow a reduction in dosage. The bacteria and other organisms normally present in the gut will metabolize some of any orally-introduced MTX, so oral doses are expected to be higher to overcome this (and other) non-therapeutic loss of the drug.

The most serious concern with MTX is its effect on the liver. Regular blood tests (quite frequently at the beginning of treatment) should be used to monitor liver function. Drinking alcohol, as should be obvious, is not generally a good thing while using this drug. If the total dosage for a patient exceeds 1.5 grams, a liver biopsy may be required by the doctor, to double-check the results of the blood tests.

Other effects include nausea, vomiting, diarrhea (see your doctor immediately for this), mouth sores (the cells inside the mouth reproduce quickly), fatigue, and many other rare side effects. Gastrointestinal effects may be reduced or eliminated by buffering oral MTX with food, but this won’t always help. RxMed’s monograph on MTX has a much more detailed and complete list of possible side effects (see link at the bottom of this page).

Due to MTX’s effect on quickly-reproducing cells, it is imperative that pregnancy be avoided while on MTX, and for at least one full menstrual cycle after stopping the drug. This warning is true for men, as well, but getting someone pregnant should be avoided for at least three months after discontinuation. Some women have become pregnant while on MTX, and the drug was stopped ASAP after this discovery. Anecdotes I’ve heard indicate that no abnormalities in the resultant children have been detected, but it’s better to avoid such gambles. Some doctors will not prescribe MTX unless the patient agrees to use two forms of contraception while on the drug.

And speaking of doctors, the most important consideration when thinking about MTX therapy is that you have a doctor who is highly experienced in using this drug. Since so many cautions exist for this drug, for pregnancy, aspirin, antibiotics, liver damage, etc., it is vital that the patient receive expert monitoring while taking MTX.

On the up side, people do exist who attribute their ability to continue walking and moving to MTX, without side effects, and some patients have gone for as long as five years without a liver biopsy at all (just regular blood work). Some have found that taking folic acid supplements will reduce some of the side effects (especially the mouth sores), but this practice can (but generally doesn’t seem to) lead to a reduction in the efficacy of the drug. There is some evidence to indicate that supplementing with folic acid actually protects the liver from some of the MTX effects.

January 12, 2001, Update: I recently learned that chemotherapy drugs like MTX can have detrimental side effects on memory. Again, when used for psoriasis, MTX is used at a much lower dosage than when fighting cancers, but some anecdotes I’ve heard relate memory problems directly to even small doses of MTX.