Antipsychotic Effects of Celecoxib Add-On Haloperidol in Schizophrenia: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Previous studies have indicated abnormalities in the immune system, such as central nervous system inflammation and high levels of activating cytokines in the cerebrospinal fluid of schizophrenic patients. Celecoxib, a modulator of proinflammatory cytokines, as an adjunctive therapy add-on risperidone (a well-established atypical antipsychotic) and amisulpiride (a benzamide antipsychotic), had improved these patients significantly.

A trial was conducted to evaluate the therapeutic effects of celecoxib add-on haloperidol, a classic antipsychotic that has been reported to have an immunomodulatory effect and mainly affects positive psychotic symptoms in schizophrenia.

In a prospective, double-blind study, after a washout period, 49 patients with schizophrenia were randomly assigned to either 15 - 30 mg/day haloperidol plus 400 mg/day of celecoxib or the same dose of haloperidol plus placebo for 5 weeks. Psychopathology was evaluated via the Positive and Negative Symptoms Scale (PANSS). The data were reported as mean ± standard deviation and frequency. An Independent t-test was carried out when comparing the data of these two groups for each week. The proportion comparison was carried out using the chi-square test. In terms of age, gender, marital and educational state, and duration or severity of disease or psychopathology and subtypes of schizophrenia, there were no significant differences.

Over 5 weeks, there was significantly greater improvement in the celecoxib group in scores on the total PANSS and on positive symptoms and general psychopathology subscales ([t = 2.89, P = 0.006], [t = 2.37, P = 0.022], and [t = 3.34, P = 0.002] respectively).

Celecoxib is an efficient adjuvant agent in the treatment of patients with schizophrenia. Significant superiority of management with a modulator of proinflammatory cytokine, which balances immune responses over haloperidol alone, reconfirms the immune dysfunction and inflammation hypothesis of schizophrenia.