Central nervous system toxicity associated with weekly low‐dose methotrexate treatment

Richard Wernick, David L. Smith

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Central nervous system (CNS) toxicity from low‐dose methotrexate (MTX) has been reported rarely, and reported symptoms consist primarily of dizziness and headache. We reviewed the records of 25 consecutive patients treated with low‐dose MTX, and found 5 who had spontaneously reported unpleasant cranial sensations, mood alteration, or memory impairment. Rechallenge with MTX on 5 occasions in 3 patients led to recurrent CNS symptoms in all cases. CNS toxicity was the sole reason for discontinuation of MTX in 2 patients. These 5 patients differed from the 20 without CNS toxicity in age (mean 68 versus 50) and baseline serum creatinine level (1.3 mg/dl versus 0.9 mg/dl), but not in weekly dosage of MTX (12 mg versus 16 mg). These results suggest that CNS toxicity is more common than previously reported, particularly in older patients with mild renal insufficiency.

Original languageEnglish (US)
Pages (from-to)770-775
Number of pages6
JournalArthritis & Rheumatism
Issue number6
StatePublished - Jun 1989

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)


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