Toxic CNS side effects of NSAIDs are far less frequent than GI or renal toxicity; however, various CNS effects include headache, cognitive difficulties, behavioral change, and aseptic meningitis. Acute psychosis has been reported with indomethacin and sulindac use and is hypothesized to result from the structural similarity of these NSAIDs to serotonin.
One of the most interesting side effects of NSAID use is aseptic meningitis. The literature reports cases in which patients repeatedly present with symptoms of headache, fever, neck stiffness, and fever within hours of taking NSAIDs. Cerebrospinal fluid analysis in these patients reveals elevated white blood cell, elevated protein, and normal or decreased glucose levels. Symptoms resolve after NSAID use is stopped and can be elicited with repeat NSAID challenges. This phenomenon is most often seen with patients who have underlying autoimmune diseases, such as systemic lupus erythematosus. The phenomenon is thought to be a hypersensitivity reaction. A complete workup to rule out infectious meningitis must be undertaken before the diagnosis of NSAID-induced aseptic meningitis is entertained.4
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