A Clinical Trial of Adjuvant Allopurinol Therapy for Moderately Refractory Schizophrenia

Miriam G. Brunstein, M.D., M.Sc.; Eduardo S. Ghisolfi, M.D., M.Sc.; Fernanda L. P. Ramos; and Diogo R. Lara, M.D., Ph.D.

Objective: To evaluate the xanthine oxidase inhibitor allopurinol as an adjuvant treatment for patients with moderately refractory schizophrenia, with the objective of increasing the endogenous pool of purines, including the neuromodulator adenosine.

Method: A double-blind, placebo-controlled, crossover clinical trial of add-on allopurinol (300 mg b.i.d.) for poorly responsive schizophrenia or schizoaffective disorder (DSM-IV criteria) was conducted. Thirty-five patients were enrolled, of whom 22 completed the 12 weeks of the study. Eighteen of these patients also completed a P50 evoked potential evaluation.

Results: Allopurinol was well tolerated and produced significant improvement in Positive and Negative Syndrome Scale (PANSS) total, positive, negative, and general scores, particularly for positive symptoms compared with baseline and with placebo phase. Nine patients improved more than 20% in PANSS total score during allopurinol treatment, whereas none responded in the placebo phase. Responders had a shorter duration of illness than nonresponders. P50 auditory sensory gating failed to improve with allopurinol treatment.

Conclusions: Allopurinol was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia, especially for refractory positive symptoms.

(J Clin Psychiatry 2005;66:213-219)

Received Feb. 9, 2004; accepted July 19, 2004. From the Department of Biochemistry, Health Basic Science Institute (Instituto de Ciências Básicas da Saúde), Federal University of Rio Grande do Sul (Universidade Federal do Rio Grande do Sul) (Drs. Brunstein and Ghisolfi); and the Departments of Biochemistry and Psychiatry, Catholic University of Rio Grande do Sul (Pontifícia Universidade Católica do Rio Grande do Sul) (Drs. Ghisolfi and Lara and Ms. Ramos), Porto Alegre, Brazil.

This research was supported by a grant from the Stanley Medical Research Institute.

The authors are grateful to the Schizophrenic Patients' Relatives Association of Rio Grande do Sul (Associação Gaúcha de Familiares de Pacientes Esquizofrênicos e Demais Doenças Mentais [AGAFAPE]), Hospital Psiquiátrico São Pedro, the National Council for Scientific and Technological Development (CNPq), Nazareno de Abreu from Fitonfarma, and especially Prof. Diogo O. Souza.

Corresponding author and reprints: Diogo R. Lara, M.D., Av. Ipiranga, 6681-Pd 12A, Porto Alegre, RS, Brazil, 90619-900(e-mail: drlara@pucrs.br).