A longitudinal study of 211 patients with schizophrenia, who underwent repeated neuroimaging over 7.2 years, found that long-term antipsychotic treatment was associated with reduced brain tissue volumes and increased cerebrospinal fluid volumes. Antipsychotic treatment intensity was linked to generalized and specific brain tissue reduction, with greater reductions in gray matter and white matter volumes. Illness severity had minimal effects, while substance abuse showed no significant association. Animal studies suggest antipsychotics may contribute to brain tissue loss. The study highlights the need for careful evaluation of antipsychotic use due to potential long-term effects on brain volume. Antipsychotic treatment was associated with progressive brain volume changes, including reductions in gray and white matter, and increases in ventricular and cerebrospinal fluid volumes. The study also found that typical antipsychotics, nonclozapine atypical antipsychotics, and clozapine had differential effects on brain volumes. The findings suggest that antipsychotic treatment may contribute to progressive brain tissue volume deficits in schizophrenia. The study underscores the importance of considering the risks and benefits of long-term antipsychotic use, particularly in light of potential neurotoxic effects. The results have implications for the use of antipsychotics in other psychiatric disorders, emphasizing the need for cautious prescribing practices.A longitudinal study of 211 patients with schizophrenia, who underwent repeated neuroimaging over 7.2 years, found that long-term antipsychotic treatment was associated with reduced brain tissue volumes and increased cerebrospinal fluid volumes. Antipsychotic treatment intensity was linked to generalized and specific brain tissue reduction, with greater reductions in gray matter and white matter volumes. Illness severity had minimal effects, while substance abuse showed no significant association. Animal studies suggest antipsychotics may contribute to brain tissue loss. The study highlights the need for careful evaluation of antipsychotic use due to potential long-term effects on brain volume. Antipsychotic treatment was associated with progressive brain volume changes, including reductions in gray and white matter, and increases in ventricular and cerebrospinal fluid volumes. The study also found that typical antipsychotics, nonclozapine atypical antipsychotics, and clozapine had differential effects on brain volumes. The findings suggest that antipsychotic treatment may contribute to progressive brain tissue volume deficits in schizophrenia. The study underscores the importance of considering the risks and benefits of long-term antipsychotic use, particularly in light of potential neurotoxic effects. The results have implications for the use of antipsychotics in other psychiatric disorders, emphasizing the need for cautious prescribing practices.