Celecoxib augmentation in patients with first episode schizophrenia and its correlation with Indoleamine 2,3-dioxygenase, Interferon-gamma, and Tumor Necrosis Factor-alpha: An open label case control study

Schizophrenia is a chronic and extremely disabling psychiatric disorder, characterized by a wide range of symptoms classified into positive, negative, and cognitive. Positive symptoms include hallucinations, delusions, and agitation, whereas negative symptoms include blunted affect, lack of volition, and disorganized speech and behaviour. Cognitive symptoms include limited executive functioning, poor attention, and restricted working memory. The onset happens during adolescence or young adulthood, and rarely in childhood. Despite progress in treatments, most patients show persistent or varying symptoms.

Neuroinflammatory hypothesis of Schizophrenia: In recent decades, numerous studies have provided evidence in support of the role of altered inflammatory responses in the etiopathogenesis of major mental illnesses including schizophrenia. The causes of schizophrenia are still mostly unknown. Some evidence highlights imbalanced network in neuroprotective/neurodegenerative factors. In schizophrenia, changes in cytokine levels and an imbalance between type 1 and type 2 immune response were observed. Reduced production of type 1 cytokines, particularly IL-2 and IFN-γ, was found in schizophrenic patients. It was observed that a reduced type 1 response occurs, mainly in the early stages of the disease, whereas an enhanced type 2 response, associated with a chronic pro-inflammatory stage, may predominate in the later stages.

Role of COX Inhibitors in Schizophrenia

COX-2 inhibitors have been shown to have beneficial additional effects to traditional antipsychotic therapy, especially in the early stages of the disease. These effects are hypothesized to be due to their ability to reduce PGE2, type 2 cytokines, production of kynurenic acid, and to strengthen glutamate transmission.

Celecoxib trials in Schizophrenia

COX inhibitors have been found to have positive effects in the treatment of psychiatric diseases when administered in combination with first-choice specific drugs. Celecoxib has been shown to hasten the onset of the effects of common therapies, on the other hand, monotherapy with COX inhibitors did not produce significant results, as it happens in some other diseases treatment.

Though the role of neuroinflammatory cytokines in pathogenesis of schizophrenia and the role of Celecoxib as an adjunctive treatment in schizophrenia, has been hypothesised since long. However, most of the studies was carried out on patients with chronic schizophrenia and results have been inconsistent so far. In few studies patients with first episode schizophrenia were studied and improvement in clinical outcome was found. How ever literature regarding efficacy of celecoxib is scarce in first episode schizophrenia. In our study we intend to see the treatment outcome of Celecoxib augmentation in first episode schizophrenia and correlate the clinical outcome with changes in levels of inflammatory markers, i.e., TNF- α, IFN- γ and Indolamine-2,3- dioxygenase (IDO). These correlations will potentiate the biological basis of the neuroinflammatory hypothesis in schizophrenia and give us potential therapeutic options for schizophrenia.