Antipsychotics are currently the predominant treatment for individuals diagnosed with schizophrenia, but there is an accumulating body of research that links the use of these drugs to structural abnormalities in the brain. A recent meta-analysis suggests that gray matter loss in the brain may depend on the dose and class of the antipsychotic.
New research, published in this month’s issue of Biological Psychiatry, reinforces the link between antipsychotic drug use in patients with schizophrenia and progressive structural brain abnormalities. Antipsychotic use has been associated, specifically, with a decrease in gray matter in the brain. Gray matter is mainly located on the brain’s surface and functions, generally, to aid in the processing of information. The loss of gray matter could represent either cell shrinkage, cell loss, or both.
Past research has found that the dose of antipsychotic is associated with decreased volume of gray matter but has not compared the impact of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). The latest study, led by Antonio Vita, set out to do just that.
Vita and his colleagues completed a meta-analysis of longitudinal MRI studies published between 2002 and 2014. Altogether, their study included the antipsychotic dose and class information as well as gray matter measurements for 1,155 patients and 911 healthy control subjects. After crunching all of the data, they found that the greater the exposure to antipsychotics, the greater the reduction in gray matter in the brain.
Patients taking FGAs or a combined treatment of both FGAs and SGAs had a significant decrease in brain volume. For these patients, greater brain volume loss was associated with a higher mean daily dose of antipsychotics.
In patients treated with just SGAs, a significant decrease in volume was not found. Previous studies have also found that SGAs have less of an effect on brain volume, yet even a smaller effect may have significant implications.
The connection between antipsychotic drugs and decreased gray matter may be strengthened by their finding that illness severity, age, and substance abuse were not associated with the reductions in brain volume.
The researchers conclude:
“Although this is a clinically meaningful result, many issues remain to be clarified: for instance, we still do not know whether the effects on the brain of antipsychotics vary as a function of age and stage of illness, or whether they may occur only when a certain threshold of exposure (daily dose or cumulative dose) is reached”
Vita, A., De Peri, L., Deste, G., Barlati, S., & Sacchetti, E. (2015). The effect of antipsychotic treatment on cortical gray matter changes in schizophrenia: does the class matter? A meta-analysis and meta-regression of longitudinal magnetic resonance imaging studies. Biological psychiatry. (Abstract)