Allopurinol for the treatment of aggressive behaviour in patients with dementia

Aggressive behaviour is commonly observed in patients with dementia, and current pharmacological treatments are still deficient in terms of efficacy and tolerability. Allopurinol is an inhibitor of the enzyme xanthine oxidase, with previously suggested anti-aggressive effects. After successful treatment of aggression in two patients, we performed a case-series study with allopurinol 300 mg a day orally for 6 weeks (increasing 300 mg every 2 weeks if the response was less than 50%) in six patients with dementia associated with prominent aggressive behaviour who failed to respond to two previous treatment strategies. Five patients were considerably responsive to allopurinol (four with 300 mg within 2 weeks and one with 600 mg), apparently without side-effects, which is in accordance with its well-established safety and tolerability profile. The observed therapeutic effect of allopurinol might be due to the inhibition of the enzyme xanthine oxidase, possibly decreasing production of oxigen-free radicals or promoting the accumulation of purines. Controlled studies are warranted to confirm these preliminary observations.

[1]  D. Souza,et al.  Allopurinol augmentation for poorly responsive schizophrenia. , 2001, International clinical psychopharmacology.

[2]  M. E. Frizzo,et al.  Activation of glutamate uptake by guanosine in primary astrocyte cultures , 2001, Neuroreport.

[3]  N. Herrmann Recommendations for the Management of Behavioral and Psychological Symptoms of Dementia , 2001, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[4]  L. Martin,et al.  N-Methyl-d-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer’s disease , 2001, Journal of the Neurological Sciences.

[5]  K. Jain Evaluation of memantine for neuroprotection in dementia , 2000, Expert opinion on investigational drugs.

[6]  D. Souza,et al.  Allopurinol for refractory aggression and self-inflicted behaviour , 2000, Journal of psychopharmacology.

[7]  C. Fairburn,et al.  Natural history of aggressive behaviour in dementia , 1999, International journal of geriatric psychiatry.

[8]  S. Schiffmann,et al.  Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor , 1997, Nature.

[9]  W. Nyhan,et al.  The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism , 1997, Journal of Inherited Metabolic Disease.

[10]  W. Shen,et al.  The American Psychiatric Press Textbook of Psychopharmacology , 1995 .

[11]  M. Delivoria-Papadopoulos,et al.  Effect of allopurinol on uric acid levels and brain cell membrane Na+,K+-ATPase activity during hypoxia in newborn piglets , 1994, Brain Research.

[12]  G. Zaccara,et al.  Allopurinol as Add‐on Therapy in Refractory Epilepsy: A Double‐Blind Placebo‐Controlled Randomized Study Italy, on his retirement. , 1994, Epilepsia.

[13]  Michael B. Smith,et al.  Allopurinol preserves cerebral energy metabolism during perinatal hypoxia-ischemia: A 31P NMR study in unanesthetized immature rats , 1992, Neuroscience Letters.

[14]  Y. Wada,et al.  Anticonvulsant effect of allopurinol on hippocampal-kindled seizures , 1992, Pharmacology Biochemistry and Behavior.

[15]  K. Arimoto,et al.  Clinical Effects of Allopurinol on Intractable Epilepsy , 1991, Epilepsia.

[16]  C. Palmer,et al.  Reduction of Perinatal Hypoxic-Ischemic Brain Damage with Allopurinol , 1990, Pediatric Research.

[17]  W. Sharp,et al.  Experimental pharmacologic cerebroprotection. , 1988, Journal of vascular surgery.

[18]  A. Harken,et al.  Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains. , 1988, The Journal of clinical investigation.

[19]  I. Ushijima,et al.  The clonidine-induced self-injurious behavior of mice involves purinergic mechanisms , 1984, Pharmacology Biochemistry and Behavior.

[20]  I. Ushijima,et al.  Involvement of adenosine receptor activities in aggressive responses produced by clonidine in mice , 2004, Psychopharmacology.

[21]  J. Newcomer,et al.  The glutamate synapse in neuropsychiatric disorders. Focus on schizophrenia and Alzheimer's disease. , 1998, Progress in brain research.

[22]  T. Dunwiddie,et al.  Role of adenosine as a modulator of synaptic activity in the central nervous system. , 1997, Advances in pharmacology.

[23]  D. Knoedler The Modified Overt Aggression Scale. , 1989, The American journal of psychiatry.

[24]  J. Endicott,et al.  The Overt Aggression Scale for the objective rating of verbal and physical aggression. , 1986, The American journal of psychiatry.