International Clinical Psychopharmacology 2001, 16:235  237 CASE REPORT Allopurinol augmentation for poorly responsive schizophrenia D.R. Lara a,b , M.G. Brunstein c , E.S. Ghisolfi a,c , M.I. Lobato c , P. Belmonte-de-Abreu c and D.O. Souza a a Department of Biochemistry, ICBS, UFRGS, Porto Alegre, b Department of Biochemistry, Faculty of Bioscience, PUC-RS, Porto Alegre and c Department of Psychiatry, HCPA, UFRGS, Porto Alegre, Brazil Correspondence to Diogo R. Lara, Departamento de Bioquımica, ICBS, UFRGS, Rua Ramiro ´ Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil Tel: +55 51 316 5557; fax: +55 51 316 5540; e-mail: drlara@plug-in.com.br Received 30 August 2000; accepted 23 January 2001 Adenosine has been proposed to contribute to the pathophysiology of schizoprenia and as a target for therapeutic intervention. In the lack of direct adenosine agonists, allopurinol may indirectly elevate adenosine levels by inhibiting degradation of purines. We report two cases of poorly responsive schizophrenic patients who improved considerably with add-on allopurinol 300 mg  day. Their clear clinical improvement warrant further investigation of allopurinol, as well as other purinergic strategies, for the treatment of schizophrenia. Int Clin Psychopharmacol 16:235 237  2001 Lippincott Williams & Wilkins Keywords: allopurinol, adenosine, purinergic system, schizophrenia INTRODUCTION Ž Augmentation strategies with lithium Schulz et al., . Ž . 1999 , carbamazepine Hesslinger et al., 1999 , val- Ž . Ž proate Hessliger et al., 1999 and selegiline Junger- . man et al., 1999 have failed to produce significant benefit beyond the efficacy of antipsychotics in the treatment of schizophrenia, whereas glycine im- Ž . proves negative symptoms Heresco-Levy et al., 1999 Ž . if not associated with clozapine Evins et al., 2000 . Still, the poor pharmacological response of many schizophrenic patients stimulates the search for new adjunctive treatments to antipsychotics. Adenosine is a neuromodulator of the purinergic system, mainly with inhibitory actions in the CNS Ž . Ralevic and Burnstock, 1998 through widespread A receptors and mesolimbic-striatal A receptors, 1 2A Ž which are colocalized with D receptors Ferre, ´ 2 . 1997 . Preclinically, adenosine and analogs exert Ž . antipsychotic Ferre, 1997 , anxiolytic, sedative, anti- ´ Ž . convulsant Ralevic and Burnstock, 1998 and anti- Ž . agressive effects Ushijima et al., 1984 . Unfortu- nately, safe and tolerable direct adenosine agonists are still not available for clinical use in humans. Recently, the combination of haloperidol with the inhibitor of the adenosine transporter dipyridamole was superior to the combination with placebo in Ž . schizophrenic patients Akhondzadeh et al., 2000 . Allopurinol is an inhibitor of purine degradation Ž . that exerts anticonvulsant Zagnoni et al., 1994 and Ž . antiaggressive Lara et al., 2000 actions, which are compatible with adenosine-enhancing effects. Our Ž group openly used add-on allopurinol 300 mg once . Ž . a day in 11 schizophrenic patients DSM-IV who were poorly responsive to conventional treatment, with unchanged antipsychotic dosages. Among these, four had no clinical response, two showed mild symptom improvement and five presented clinically relevant improvement evaluated by Clinical Gobal Impression. We report two of these cases with DSM- IV undifferentiated schizophrenia, which were properly followed with psychopathological scales and Ž significantly improved with add-on allopurinol 300 . mg once a day with unchanged antipsychotic dosages. CASE REPORTS Case 1 A 43-year-old male with schizophrenia since the age of 16 years and 19 psychiatric admissions presented 0268-1315  2001 Lippincott Williams & Wilkins International Clinical Psychopharmacology 2001, Vol 16 No 4 235