Valproate Treatment for Schizophrenia

Congratulations on your first, first-author paper Thomas! Thomas is a PhD candidate in IMAGE Otago who has recently moved to Canberra to study medicine. Below is a summary of Thomas' paper - if you would like to read the paper in full, please see the link at the bottom of the page. 

When it comes to treating schizophrenia, a complex condition affecting about 0.5% of the global population, the medication journey can be incredibly challenging. For some patients, standard, first-line antipsychotics don't work. When this happens, doctors turn to a powerful medication called clozapine. If schizophrenia only responds to clozapine, it is called Treatment-Resistant Schizophrenia (TRS). But what happens when even clozapine isn't enough?

When a patient’s symptoms persist despite taking clozapine, doctors categorise this as Ultra-Treatment-Resistant Schizophrenia (UTRS). To help relieve residual symptoms, psychiatrists often prescribe a second medication alongside clozapine, a strategy called augmentation therapy. One of the most common add-on medications is valproate (a mood stabiliser). 

While valproate is frequently used to help stabilise patients, we haven't fully understood what this combination actually does to the physical structure of the brain. Thomas used Magnetic Resonance Imaging (MRI) to look at the brains of individuals taking clozapine alongside valproate, comparing them to individuals taking clozapine without valproate. 

For individuals taking valporate: 

• There were noticeable decreases in whole-brain volume and white matter volume. Thomas also found changes in fractional anisotropy (FA), which is a scientific measurement for how healthy the white matter is. 

• Conversely, Thomas also found hypertrophy (enlargement) of grey matter in the cerebellum and the brainstem. The cerebellum is the area at the base of the skull responsible for motor control, balance, and complex cognitive processing.