“The role played by antipsychotic treatment on the pathophysiologic trajectory of brain abnormalities in schizophrenia is currently a matter of lively debate,” said Dr. Antonio Vita, a professor of psychiatry at the University of Brescia in Italy, and director of the psychiatric unit at Spedali Civili Hospital.
What is clear, he says, is that research collected from cross-sectional and longitudinal magnetic resonance imaging studies shows that patients with schizophrenia show progressive structural brain abnormalities. The findings indicate that lower gray matter volume or greater loss of gray matter over time are associated with the duration of antipsychotic treatment or cumulative antipsychotic intake.
However, he noted that most of the past studies did not take into account the impact of whether a patient was prescribed first-generation or second-generation antipsychotics. These two classes of drugs are equally effective, but have different pharmacological properties and, therefore, work differently in the body.
That led Vita and his research team to compile data from 18 imaging studies, which included 1,155 patients with schizophrenia and 911 healthy control subjects, to evaluate the influence of the type of antipsychotic drug on gray matter changes over time.
As expected, the analysis confirmed that patients with schizophrenia show progressive cortical gray matter loss relative to healthy people, the researchers reported. This is related to the continued use of antipsychotic medications during the interval between imaging scans, they explained.
They also found that greater gray matter loss was correlated with a higher daily dose in patients treated with first-generation antipsychotics. Less progressive loss was observed in studies that included only patients treated with second-generation antipsychotics, the researchers said.
This is consistent with the results of several studies in animals and some clinical studies with patients indicating that second-generation antipsychotics may have a neuroprotective effect on the brain, according to the new study, which was published in Biological Psychiatry.
“The possibility that antipsychotic medications might have long-term effects on brain structure or function that might be beneficial or detrimental is an important issue deserving further study as many people treated with these medications will remain on them for several decades,” said Dr. John Krystal, editor of Biological Psychiatry.
“Although this is a clinically meaningful result, many issues remain to be clarified,” added Vita. “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.”
“Clarification of these issues will have crucial importance in the clinical management of schizophrenia and will allow a better understanding of the mechanisms underlying the progression of structural brain abnormalities in the disease,” he said.