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Methotrexate is an antimetabolite drug that has been in use since the 1950s and it continues to be one of the most widely prescribed drugs used to treat severe psoriasis. Methotrexate is effective against diseases that are affected by abnormally rapid cell growth (such as psoriasis, rheumatoid arthritis and cancer). It helps to control psoriasis affecting your skin, nails, and joints. Methotrexate is usually given after other medications have been tried unsuccessfully.

How the treatment works

  • The mechanism of action is the interference with DNA synthesis repair and cellular reproduction.
  • Antifolate agents, such as methotrexate, impair the function of folic acid (a B vitamin) that is essential for cellular activity.
  • Methotrexate is usually given once a week orally (pills) at doses ranging from 2.5 mg to 25 mg or occasionally by injection (with a needle).
  • It can be administered either as a single dose or in a split dose 12 hours apart for 3 doses.


  • Effective, convenient to take and relatively inexpensive
  • Improvements are noticeable following 6-8 weeks of therapy
  • Methotrexate can be used for longer periods of time in comparison with other agents (such as cyclosporine), but patients must be regularly monitored for potentially serious side-effects.


  • Side-effects include headache, skin irritation (itch and rash), hair loss, mouth sores, upset stomach, nausea, low white blood cell count and fatigue.
  • Methotrexate can cause serious liver damage. Routine blood tests for liver function may not detect the damage, so a liver biopsy may be necessary every 1.5-2 years while undergoing treatment.
  • Long-term risks include birth defects, kidney damage, bone marrow toxicity and bone marrow suppression.
  • There are many other medicines that can interact with methotrexate.
  • Methotrexate can cause birth defects and miscarriages, so women taking the drug must use a reliable method of birth control.

Comments & Suggestions

  • It is imperative that your doctor educates you about the potential risks of this medicine.
  • Side-effects must be reported to your doctor to help you manage the symptoms.
  • To monitor your progress, you must attend regularly scheduled clinic visits and do not miss any blood tests that are requisitioned by your doctor.
  • Make certain that you understand and follow the instructions for use.
  • To reduce the chance of liver damage, do not consume alcohol while on therapy.
  • Your doctor may ask you to take folic acid supplements to protect the liver.
  • Drink plenty of fluids while taking methotrexate.