Allopurinol as Adjuvant Therapy in Poorly Responsive or Treatment Refractory Schizophrenia

Abstract

Objective: To review the available literature evaluating the effectiveness of allopurinol for poorly responsive or treatment refractory schizophrenia. Data Sources: Searches of MEDLINE (1966–October 2006), the Cochrane Library, and International Pharmaceutical Abstracts (1970–October 2006) were conducted using the terms allopurinol and schizophrenia. Limits were set to select studies conducted in humans. Study Selection and Data Extraction: All articles identified from the data sources were evaluated. All case reports or clinical trials located were included in the review. Data Synthesis: Dopamine has been implicated for many years in the pathophysiology of schizophrenia, and the typical antipsychotics, via blockade of dopaminergic neurotransmission, have provided relief for patients with positive symptoms. However, because dopamine blockade does not relieve all symptoms of schizophrenia, it is now evident that many neurotransmitters may be involved in the pathogenesis of schizophrenia. Therefore, atypical antipsychotics, which target multiple neurotransmitters, have emerged as first-line therapies. An evolving body of evidence also supports a purinergic hypothesis for schizophrenia. Increased adenosinergic transmission is thought to reduce the affinity of dopamine agonists for dopamine receptors. Allopurinol, a xanthine oxidase inhibitor, may increase circulating pools of adenosine and may ultimately have antipsychotic and anxiolytic effects. Growing evidence for use of allopurinol as adjunctive therapy has been reported in both case reports and small clinical trials. Conclusions: Clinical trials show that adjuvant allopurinol may provide benefit to patients who are poorly responsive to current treatments for schizophrenia. Allopurinol is well tolerated by most patients. However, larger, randomized clinical trials need to be performed to determine the magnitude of this benefit, whether allopurinol should be routinely used as adjuvant therapy to antipsychotics, and which patient population is most likely to benefit from allopurinol use. For patients with limited options, allopurinol in doses of 300 mg once or twice daily may improve psychotic symptoms, especially refractory positive symptoms.