NSAIDs Side Effects

OB/GYN News, Oct 1, 2001 by Sally Koch Kubetin

Dramatic psychiatric symptoms have been reported occasionally in patients taking nonsteroidal anti-inflammatory drugs.

Symptoms usually resolve promptly when the drugs are discontinued, but in at least one scenario--the concurrent use of an NSAID with lithium--severe toxicity is a danger. NSAIDs markedly reduce lithium clearance, increase blood levels, and can lead to toxicity within 2-3 days, Dr. Norman Sussman said.

The reports in the literature "are anecdotal and do not establish a causal role for NSAIDs," said Dr. Sussman of New York University at a conference on psychopharmacology sponsored by the university.

One report described four patients who developed moderate to severe depression (accompanied by paranoia in one case) on NSAID therapy which remitted when the drug was discontinued and returned when the drug was restarted in three of the cases.

Five case reports involved psychiatric outpatients (with major depressive disorder, bipolar disorder, schizophrenia, and anxiety disorder) who were prescribed NSAIDs for painful musculoskeletal conditions. All developed moderate to severe depression. Four who had suicidal thoughts attempted suicide. Symptoms remitted when the drugs were stopped and returned with reuse.

With final discontinuation of the drugs, all patients eventually returned to baseline mental states, Dr. Sussman said.

"We need to think about NSAIDs when a patient presents with new onset or worsening symptoms, given how widely these drugs are taken. As part of intake, I routinely ask about pain medications," said Dr. Sussman, clinical professor of psychiatry at the university. Such vigilance is particularly indicated for older patients and those with arthritis or other musculoskeletal disorders.

NSAIDs inhibit the synthesis of prostaglandins, notably cyclooxygenase-1 and cyclooxygenase-2, which are found in the brain. These substances influence neuronal connectivity and CNS development as well as learning and memory.