COX-2 inhibitors as adjunctive therapy in schizophrenia

Cyclooxygenase-2 (COX-2) is constitutively expressed in the central nervous system, and is thought to have an important functional role therein. COX-2 interacts with neurotransmitters such as acetylcholine, 5-hydroxytryptamine and glutamate but is also involved in the regulation of the central nervous system immune system and in inflammation via the effects of prostaglandins, in particular prostaglandin E2. A general therapeutic effect of the COX-2 inhibitor celecoxib on symptoms of schizophrenia was observed during a prospective, randomised, double-blind study of celecoxib add-on treatment to the atypical antipsychotic risperidone. The results from this trial of adjunctive therapy with a COX-2 inhibitor in schizophrenia are encouraging, and the findings support the view that an immunological/inflammatory process is involved in the pathogenesis of the disease. The add-on to an antipsychotic design of the study was chosen due to ethical reasons; in less acute schizophrenic states a monotherapy with COX-2 inhibitors would be interesting. From a theoretical point of view, other psychiatric indications for selective COX-2 inhibitors are discussed. COX-2 inhibitors have failed to show therapeutic effects in Alzheimer's disease but studies from basic research and a clinical perspective suggest it has an effect on disturbed cognition. In depression, however, signs of inflammation have been described for many years. Although results of clinical studies with COX-2 inhibitors in depression are still lacking, clinical improvement of a depressive syndrome has been observed in patients who have been treated with the COX-2 inhibitor rofecoxib due to other indications. These preliminary clinical data are encouraging for clinical therapeutic effects of the selective COX-2 inhibitors in psychiatric disorders, although these effects have to be confirmed in larger clinical studies.