June 16, 2000 Researchers have discovered that it is possible to have a medication that effectively treats schizophrenia while only lasting intermittently in the brain, thus reducing the prominent side effects traditionally associated with the antipsychotic drugs used to treat this severe illness.
The study, published in the June issue of the Archives of General Psychiatry, was conducted by researchers at the Centre for Addiction and Mental Health (CAMH) and the University of Toronto. The research opens the door to significant changes in how schizophrenia is treated.
"This is a significant finding because until now it was thought that in order for antipsychotic medications to be effective, they needed to be present continuously in the brain. This study fundamentally changes our understanding of how these drugs need to work," says Dr. Robert Zipursky, Clinical Director of the Schizophrenia and Continuing Care Program at the Centre for Addiction and Mental Health and Associate Professor of Psychiatry at the University of Toronto.
It is believed that antipsychotic drugs work by binding themselves to dopamine D2 receptors in the brain. Using positron emission tomography (PET), a brain imaging technique that makes it possible to measure the amount of medication in the brain, the CAMH / U of T research group previously demonstrated that antipsychotic medications need to occupy over 60% of the brain's D2 dopamine in order to be effective.
In this most recent study carried out by Dr. Zipursky, lead author Dr. Shitij Kapur and their research team, they found that when assessed 2-3 hours after the last dose of new antipsychotic medication, approximately 60% of the D2 receptors are occupied. However, 12 hours after the last dose, very little of the antipsychotic medication was bound to D2 receptors. These results suggest that antipsychotic medication can still be effective without having to remain at the target receptor site for a long period of time.
"Someone could receive the antipsychotic medication at night and be ready to function during the day without uncomfortable daytime side effects," says Zipursky. For years, psychiatrists have been battling to find medications for schizophrenia that do not have the prominent side effects frequently associated with these medications - including stiffness, restlessness and tremor - which often contribute to people's reluctance to stay on their medications. Zipursky says that the results of this study show that it is possible to design many more drugs in the future which need only act briefly on the brain, can be better tolerated and in turn contribute to improved functioning. This study was funded in part by Xeneca Pharmaceuticals.
The Centre for Addiction and Mental Health is Canada's largest centre in the area of mental health and addictions. A World Health Organization Centre of Excellence and a teaching hospital fully affiliated with the University of Toronto, the Centre was established in 1998 through the merger of the Addiction Research Foundation, the Clarke Institute of Psychiatry, the Donwood Institute and the Queen Street Mental Health Centre.
Steven de Sousa
U of T Public Affairs
CAMH Public Affairs
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