Review of: Mousavi et al, J Child Adolesc Psychopharmacol 2017; 27(6):494–500

Emotional stress can trigger an inflammatory cascade response and increase blood levels of proinflammatory cytokines—including IL-1, IL-6, and tumor necrosis factor (TNF-α). These same inflammatory markers intensify in acute episodes of depression and mania. So, would blocking the inflammatory cascade aid in treating acute episodes of mood disorders?

Celecoxib works by selective inhibition of cyclooxygenase-2 and reducing prostaglandin synthesis. The authors of this research demonstrated positive benefit during trials of celecoxib as an adjunctive treatment in adults with acute bipolar mania, obsessive compulsive disorder, and depression. This study explores the safety and efficacy of celecoxib in treating acute mania in adolescents.

This study was an 8-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial conducted at an inpatient psychiatric hospital with 40 adolescents (ages 12–17). The subjects met criteria for a moderate to severe episode of bipolar mania without psychosis. In the treatment protocol, all adolescents received treatment with lithium (target blood level of 0.8–1.1) and risperidone (1 mg per day, then increasing to 3 mg per day). The treatment group also received celecoxib (100 mg twice daily), while the control group received a placebo over an 8-week period. Treatment started in the hospital setting, then continued in an outpatient clinic when the patients were ready for discharge.

The primary outcome was change in the Young Mania Rating Scale (YMRS), measured at baseline and at weeks 2, 4, and 8. At week 8, there was a significant difference in the change in YMRS scores between the celecoxib and control groups (p = 0.04). A secondary outcome measured was the Clinical Global Impressions—Improvement (CGI-I) scale: There was a trend in favor of the celecoxib group that did not reach significance (p = 0.09). For the safety analysis, the most common adverse events reported were increased appetite and dry mouth, but there were no significant differences between the two groups in any of the reported adverse events. Cardiovascular health was also monitored by physical exam and electrocardiogram, which remained normal throughout the study.

CCPR’s take
While the idea of reducing inflammation as part of the treatment regimen for a manic episode shows promise, more research is necessary before recommending use of celecoxib. The data show that celecoxib may be helpful in the acute treatment of a mood episode, but how long should treatment last? Should we follow blood levels of inflammatory markers to guide treatment? What are the risks of longer-term treatment? More studies are needed to answer these questions.