Kara Dempster
Imagine you are hearing voices and experiencing paranoid delusions. Now imagine you were told that there was treatment for those symptoms. You anticipate relief finally. Now imagine that the treatment the experts offer you does not work. You wonder if they have gotten the diagnosis wrong. This is the plight of an individual with treatment resistant schizophrenia.
My name is Kara Dempster and I am an early career clinician researcher at Dalhousie University in Halifax Nova Scotia with an interest in elucidating the underlying neurobiological correlates of treatment resistant schizophrenia.
A third of individuals with schizophrenia do not respond to first line antipsychotic treatments and meet criteria for treatment resistant schizophrenia, the majority being poor responders from their first episode of psychosis. The evidence for clozapine is unequivocal in this group. Despite this, it is vastly underutilized. In an ideal world, individuals could be offered clozapine from the onset of their illness, or even after a single failed antipsychotic trial.
The issue of determining clozapine eligibility is of particular importance in early phase psychosis as the response to clozapine is more robust. In addition, the onset of psychosis occurs during a crucial developmental period. It is simply harder to get back on track developmentally if one has missed out on normative functional experiences due to severe mental illness at this critical time.
It has been hypothesized that there may be two subtypes of schizophrenia; one characterized by good response to dopamine blocking treatments, and the later being resistant to this pharmacology. Several studies have found that elevated glutamate in early psychosis is associated with poorer response to treatment at various discrete intervals. To date, no one has examined the association of elevated glutamate in early phase psychosis, and eligibility for clozapine.
In breast cancer, for example, each individual is not offered the same treatment. Treatment choices are based off the type of cancer, and other factors like hormone receptor status. Offering someone a medication that does not at all address the underlying cause of their symptoms seems grossly inadequate in comparison. The ability to use brain based measures to predict who would benefit from clozapine treatment would allow us to offer appropriate individuals this disease modifying treatment earlier in the course of illness.
In conclusion, our current process of offering all individuals with schizophrenia the same medication without any consideration of underlying neurobiology is antiquated and contributes to prolonged suffering and disability. Elevated glutamate may be one marker of treatment resistant schizophrenia. I invite you to come see my poster on Tuesday April 1. I will be presenting my work on “The Association of Anterior Cingulate Cortex Glutamate and Clozapine Eligibility in an Early Psychosis Sample”.
