This study investigates the long-term effects of antipsychotic treatment on brain volume changes in patients with schizophrenia. The researchers examined 211 patients with schizophrenia who underwent repeated MRI scans over an average of 7.2 years. The study found that longer follow-up periods were associated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Higher intensity of antipsychotic treatment was linked to generalized and specific brain tissue reduction, with smaller gray matter volumes and progressive white matter volume decrement, particularly in the putamen. Illness severity had modest correlations with tissue volume reduction, while substance abuse did not show significant associations. The findings suggest that antipsychotics may contribute to brain tissue loss over time, highlighting the importance of careful risk-benefit assessments of dosage and duration of treatment.This study investigates the long-term effects of antipsychotic treatment on brain volume changes in patients with schizophrenia. The researchers examined 211 patients with schizophrenia who underwent repeated MRI scans over an average of 7.2 years. The study found that longer follow-up periods were associated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Higher intensity of antipsychotic treatment was linked to generalized and specific brain tissue reduction, with smaller gray matter volumes and progressive white matter volume decrement, particularly in the putamen. Illness severity had modest correlations with tissue volume reduction, while substance abuse did not show significant associations. The findings suggest that antipsychotics may contribute to brain tissue loss over time, highlighting the importance of careful risk-benefit assessments of dosage and duration of treatment.