Treatment of Alzheimer’s Disease

To the Editor: Research on the use of nonsteroidal anti-inflammatory drugs to delay the onset or slow the progression of Alzheimer’s disease was noted in the APA practice guideline (1). The use of these drugs for a possible neuro­protective effect against Alzheimer’s disease was not recommended for now because the evidence for such protection is primarily epidemiological, with one pilot study. The side effects of nonsteroidal anti-inflammatory drugs were not mentioned.

Gastrointestinal and renal complications are the best-known and -researched side effects of these drugs. While there have been a few case reports of psychiatric side effects induced by nonsteroidal anti-inflammatory drugs, there have never been systematic studies of these side effects (2). I reported recently on four male psychiatric patients (one with a diagnosis of bipolar affective disorder, two with recurrent major depression, and one with paranoid schizophrenia) who developed severe depression and, in some instances, suicide ideation and paranoia with use of nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen, and naproxen). These were reproducible syndromes, stopping when the drugs were discontinued and recurring on rechallenge (except for one patient who declined a rechallenge) (3).

Given the epidemiological findings, clinical trials of nonsteroidal anti-inflammatory drugs in delaying the onset or slowing the rate of progression of Alzheimer’s disease will be proposed. This is an opportune time to include in these trials assessment of possible psychiatric side effects of the drugs. If these assessments are not done, we may run the risk of patients beginning long-term treatment with nonsteroidal anti-inflammatory drugs without our understanding further the risk/benefit ratio of these drugs.