CELECOXIB (CELEBREX)

BackgroundCelecoxib was introduced in the U.S. in 1999 as a drug for pain and inflammation and has become one of the most widely prescribed drugs. It is available by prescription in capsules of 50mg, 100mg, 200mg, and 400mg.

Mechanism of Action

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that selectively targets the cyclooxygenase-2 (COX-2) enzyme; thus, in theory, maintaining its anti-inflammatory and analgesic properties but reducing sideeffects on the GI tract. It is not as selective a COX-2 inhibitor as rofecoxib (Vioxx), which was taken off the market in 2004 because of cardiovascular complications, including myocardial infarctions. Nevertheless, celecoxib has a black box warning because of possible cardiovascular and GI side effects.

Use in Schizophrenia

Five double-blind, placebo studies have been carried out with mixed results. A study of 50 patients undergoing an acute exacerbation of their symptoms reported a significant improvement in their PANSS total score using 400mg/day for 5 weeks; a reanalysis showed that it had the most effect in patients with an illness of less than 2 years’ duration.14 A follow-up study of 40 patients using 400mg/day for 8 weeks reported no overall effect; however, a reanalysis showed that patients with an illness of less than 2 years showed the most improvement.15 One study of 35 patients with chronic schizophrenia, average duration of illness 20 years and using 400mg/day for 8 weeks, reported negative results,16 but another trial of 60 patients with chronic schizophrenia, average duration of illness 8 years and “in an active phase of illness,” also using 400mg/day for 8 weeks, reported a significant improvement in positive and total symptoms on PANSS.17 Most recently, a study of 49 individuals with first-episode schizophrenia (symptoms of less than 2 years’ duration), using 400mg/day for 6 weeks, reported significant improvement in negative and total symptoms on PANSS.18

Use in Bipolar Disorder

We are aware of only one study. Twenty-eight patients with bipolar disorder, in a depressed or mixed phase, were treated with 400mg/day for 6 weeks. Compared to the placebo controls, those on celecoxib had a trend toward decreased depression at the end of the first week, but the difference between the groups was not maintained for the remaining weeks of the trial.19 SMRI is supporting a trial in progress for 80 patients with bipolar depression. Another COX-2 inhibitor, cimicoxib, was used in a large European study of unipolar depression.

Assessment

Celecoxib may turn out to be a useful ancillary drug for schizophrenia for patients with recent-onset disease, but it is probably not useful for patients who have been sick for more than two years. However, given the unknowns regarding its cardiovascular and GI risks, it should be used with much caution. As in all treatment-related decisions, the possible therapeutic benefit should clearly outweigh the risks. It is also possible that other NSAIDs that have some selectivity for COX-2 will prove useful, but they have not yet been tested.