Further evidence that COX-inhibitors such as Pfizer’s celecoxib (Celebrex) may have a second life ahead of them as adjunctive therapies in schizophrenia and other psychiatric disorders comes from a double-blind, placebo-controlled trial conducted by Shahin Akhondzadeh and colleagues at Tehran University of Medical Sciences in Iran.

Previous studies have suggested a role for celecoxib in psychiatric disorders, based on the premise that conditions such as schizophrenia stem from an immunological/inflammatory process and may therefore benefit from the involvement of cyclooxygenase-2 (COX-2) in the regulation of immune responses and inflammation in the central nervous system.

COX-2 inhibitors such as celecoxib limit the production of inflammatory cytokines, and one hypothesis for the cause of schizophrenia is chronic activation of macrophages and T-lymphocytes along with an excess of interleukin-2 and other cytokine secretions, Akhondzadeh et al noted. To explore this relationship, they gave 60 patients with chronic schizophrenia either 6mg/day of the antipsychotic risperidone plus celecoxib 400mg/day or risperidone 6mg/day plus placebo for a period of eight weeks.

Combo superiority over risperidone alone

While there were significant reductions in positive, negative and general psychopathological symptoms in both treatment groups over the course of the trial, the combination of risperidone and celecoxib was markedly superior to risperidone alone in the treatment of positive symptoms and general psychopathology symptoms, as well as in total Positive and Negative Syndrome Scale (PANSS) scores, the researchers reported in the journal Schizophrenia Research (2007; 90: 179-185). Mean Extrapyramidal Symptoms Rating Scale scores were higher in the placebo than in the celecoxib group, but these differences were not regarded as statistically significant.

The study results indicated that celecoxib might be an effective adjuvant in the management of chronic schizophrenia, perhaps reflecting “a complex interplay between the anti-inflammatory effects and the modulation of glutamatergic and dopaminergic systems by the COX-2 inhibitor," Akhondzadeh et al concluded.

This early research suggests another fruitful avenue of development for the COX-2s as they begin to shake off the association with serious cardiovascular side-effects that led to the withdrawal of Merck & Co’s Vioxx (rofecoxib) and Pfizer’s own Bextra (valdecoxib). The risk-benefit profile of Celebrex was endorsed by advisers to the US Food and Drug Administration last November when they recommended approval of the COX-2 inhibitor for the treatment of juvenile rheumatoid arthritis.