Introduction: Exposure to antipsychotic medication has been extensively associated with structural brain changes in the basal
ganglia (BG). Traditionally antipsychotics have been divided into first and second generation antipsychotics (FGAs and SGAs) however,
the validity of this classification has become increasingly controversial. To address if specific antipsychotics induce differential effects on
BG volumes or whether volumetric effects are explained by FGA or SGA classification, we reviewed longitudinal structural magnetic
resonance imaging (MRI) studies investigating effects of antipsychotic monotherapy. Material and Methods: We systematically searched
PubMed for longitudinal MRI studies of patients with schizophrenia or non-affective psychosis who had undergone a period of antipsychotic
monotherapy. We used specific, predefined search terms and extracted studies were hand searched for additional studies. Results:
We identified 13 studies published in the period from 1996 to 2011. Overall six compounds (two classified as FGAs and four as SGAs)
have been investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine, and quetiapine. The follow-up period ranged
from 3-24 months.
Unexpectedly, no studies found that specific FGAs induce significant BG volume increases. Conversely, both volumetric increases and
decreases in the BG have been associated with SGA monotherapy. Discussion: Induction of striatal volume increases is not a specific
feature of FGAs. Except for clozapine treatment in chronic patients, volume reductions are not restricted to specific SGAs.
The current review adds brain structural support to the notion that antipsychotics should no longer be classified as either FGAs or SGAs.
Future clinical MRI studies should strive to elucidate effects of specific antipsychotic drugs.