Allopurinol for the treatment of aggressive behaviour in patients with dementia

Abstract

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 oxygen-free radicals or promoting the accumulation of purines. Controlled studies are warranted to confirm these preliminary observations.

Adenosine hypothesis of schizophrenia – Opportunities for pharmacotherapy

“…They suggested that a dysfunction inpurinergic systemwould result in reduced adenosinergic activity as a possible common explanation for the imbalance between dopaminergic and glutamatergic neurotransmission and the dysregulation of neuro-immunological interaction that are characteristic hallmarks of schizophrenia (Lara et al, 2006; Lara and Souza, 2000). The hypothesis was largely based on preliminarydata suggesting a beneficial therapeutic activity of the purine derivative allopurinol in patients with schizophrenia and a moderateefficacy against aggressive behaviour(Lara et al, 2000; Lara et al, 2001; Lara et al, 2003). Next, we will review the support for the adenosine hypothesis of schizophrenia by highlighting adenosine's interactions with dopaminergic and glutamatergic neurotransmission, as well as its possible roles in the neurodevelopmental aspects of disease aetiology.…”

Allopurinol in Dermatology

“…[15] Allopurinol has likewise been found helpful in the treatment of aggressive behavior in patients with dementia in a case-series study. [16] Although this antioxidant activity of allopurinol has received little attention in dermatology, it may have potential application for the treatment of skin diseases.…”

The Role of the Guanine-Based Purinergic System in Seizures and Epilepsy

“…For example, we have demonstrated that allopurinol, a xanthine oxidase inhibitor, was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia, refractory aggressive behavior and mania [125][126][127][128][129]. These results were confirmed by an independent group [130,131] and are hypothesized to be due to an indirect increase in extracellular purine levels (adenosine and guanosine) [12].…”