CNS Adverse Effects of Nonsteroidal Anti-Inflammatory Drugs : Therapeutic Implications

It is difficult to obtain valid estimations of the true incidence of CNS effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs) from spontaneously reported adverse reactions. This is because the reporting rates of adverse reactions are low and the total number of individual drugs prescribed is not generally documented. However, some prospective studies have validated an association between NSAIDs and CNS adverse effects.Aseptic meningitis is the most widely recognised CNS adverse effect associated with NSAIDs. In several case studies, the association has been validated by rechallenge with the NSAID in question. Patients with systemic lupus erythematosus are at an increased risk of NSAID-induced aseptic meningitis, and the meningitis may be a specific cell-mediated immune response.Evidence for an association between NSAIDs and psychiatric adverse effects is mainly anecdotal and comes from spontaneous reports. In some cases, rechallenge with the NSAID strengthens the association. Cognitive dysfunction is also reported, most commonly with indomethacin, with some prospective studies strengthening this association. In contrast, other studies report beneficial CNS effects of NSAIDs, including improvement in short term memory and a protective effect in Alzheimer's disease.In patients presenting with meningitis-like symptoms, NSAID use should be considered as a possible precipitating factor. The possibility of NSAID use as an exacerbating factor in psychiatric and cognitive dysfunction should also be considered, particularly in the elderly.