Apr. 3, 2000 Using advanced brain imaging techniques, researchers at the University of Toronto and the Centre for Addiction and Mental Health (CAMH) have discovered how to treat schizophrenia with lower doses of medication - and fewer side effects.
"Our research clearly shows that we can treat schizophrenia with lower dosage levels of antipsychotic medication than was commonly thought. This research was made possible through new brain imaging technology," says Dr. Shitij Kapur, associate professor of psychiatry at U of T and deputy head of research in the schizophrenia program at CAMH who led the study published in the April issue of the American Journal of Psychiatry.
"This study has major implications for the treatment of people with schizophrenia. It's now conceivable that we can help reduce the negative side effects often experienced by people being treated for schizophrenia because we can prescribe lower doses of antipsychotic medication and achieve similar treatment outcomes."
Current treatments for the mental disorder focus on blocking the transmission of dopamine, a "feel-good" chemical in the brain that helps regulate learning, memory, emotion and cognition. In order for neurotransmission to occur, the dopamine must attach to dopamine receptors on other neurons. By blocking the dopamine from reaching these receptors, the drugs are able to reduce the symptoms of schizophrenia.
Kapur and colleagues blocked different levels - between 39 and 87 per cent - of dopamine receptors in 22 patients, as shown by a new brain imaging technique called positron emission tomography (PET) scanning. By examining the clinical effects in these patients, the researchers found that blocking 65 per cent of the receptors was sufficient for treatment while a higher level of blockade - over 80 per cent - was invariably associated with side effects. According to Kapur, this data shows patients should be treated with doses that utilize this natural window between 65 and 80 per cent blockade. Interestingly, he adds, this window is reached with doses as little as one-tenth of doses used in the past.
"Many schizophrenia patients have complained of feeling "doped up" and overly sedated when taking antipsychotic medications," says Kapur, also a research scientist at the Baycrest Centre for Geriatric Care. "They can't think clearly and have too many side effects. This study could change that."
This new understanding should not only help doctors make better decisions when prescribing antipsychotic medications, but also direct researchers toward designing new drugs that can operate within the threshold window and not exceed it, thus eliminating negative side effects. "It seems nature is on our side," adds Kapur, the study's lead author. "Fortunately, the therapeutic effects kick in at a lower threshold than the side effects. This provides important information to exploit in future drug development."
A teaching hospital fully affiliated with U of T, the Centre for Addiction and Mental Health is the largest mental health and addictions facility in Canada, only one of four such facilities in that field to receive designation from the World Health Organization as a Centre of Excellence. This study was supported by the Medical Research Council of Canada, the National Alliance for Research in Schizophrenia and Depression and the EJLB Foundation.
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