Lithium Interaction With the Cyclooxygenase 2 Inhibitors Rofecoxib and Celecoxib and Other Nonsteroidal Anti-Inflammatory Drugs
J Clin Psychiatry 2003;64(11):1328-1334
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: Nonsteroidal anti-inflammatory drugs
(NSAIDs) have been reported to increase serum lithium
concentrations. We sought to determine whether NSAIDs that
selectively inhibit cyclooxygenase (COX) 2 also elevate serum
Method: The U.S. Food and Drug Administration's
Adverse Event Reporting System (AERS) database was searched in
January 2003 for reports of interactions between lithium and
rofecoxib or celecoxib, the selective COX-2 inhibitors marketed
in the United States. Additionally, a literature search was
performed using PubMed with the MeSH terms anti-inflammatory agents, nonsteroidal and lithium. Reports of
interactions between NSAIDs and lithium were selected for review
based on titles of retrieved citations.
Results: Eighteen cases of increased serum
lithium concentrations after the addition of one of the COX-2
inhibitors to stable lithium therapy were retrieved from AERS, 13
with rofecoxib and 5 with celecoxib. Serum lithium concentration
increases of up to 99% and 448% with concomitant celecoxib and
rofecoxib use, respectively, were reported. Thirty-six
English-language literature articles report interactions between
lithium and various NSAIDs. Although some articles report no
effect or decreased serum lithium concentrations with concomitant
aspirin or sulindac, increased serum lithium concentration
reports exist for aspirin, sulindac, and 14 other NSAIDs,
including celecoxib and rofecoxib.
Conclusion: Clinicians should consider NSAID use
in the differential diagnosis of lithium toxicity, monitor
patients' serum lithium concentrations during the initiation or
discontinuation of NSAID therapy, and be aware that the selective
COX-2 inhibitors can increase serum lithium concentrations
leading to toxicity.