Beneficial antipsychotic effects of allopurinol as add-on therapy for schizophrenia: a double blind, randomized and placebo controlled trial

Abstract

There is a large amount of data showing that adenosine plays a role opposite to dopamine in the brain. Adenosine agonists and antagonists produce behavioral effects similar to dopamine antagonists and dopamine agonists, respectively. Allopurinol, a well-known hypouricemic drug that inhibits xantine oxidase, has been used as an add-on drug in the treatment of poorly responsive schizophrenic patients. Indeed, the neuropsychiatric effects of allopurinol in schizophrenia have been suggested to be secondary to its inhibitory effect of purine degradation, enhancing adenosinergic activity. The purpose of the present investigation was to assess the efficacy of allopurinol as an adjuvant agent in the treatment of chronic schizophrenia in an 8-week double blind and placebo controlled trial. Eligible participations in the study were 46 patients with schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV criteria for chronic schizophrenia. Patients were allocated in a random fashion, 23 to haloperidol 15 mg/day plus allopurinol 300 mg/day and 23 to haloperidol 15 mg/day plus placebo. Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and allopurinol showed a significant superiority over haloperidol alone in the treatment of positive symptoms, general psychopathology symptoms as well as PANSS total scores. The means of Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the allopurinol group over the trial, and the differences were significant in weeks 6 and 8. A significant difference was observed between the overall mean biperiden dosages in two groups. The results of this study suggest that allopurinol may be an effective adjuvant agent in the management of patients with chronic schizophrenia. Nevertheless, results of larger controlled trials are needed, before recommendations for a broad clinical application can be made.