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A systematic review of the effects of antipsychotic drugs on brain volume

  • J. Moncrieff (a1) and J. Leo (a2)

People with schizophrenia are often found to have smaller brains and larger brain ventricles than normal, but the role of antipsychotic medication remains unclear.


We conducted a systematic review of magnetic resonance imaging (MRI) studies. We included longitudinal studies of brain changes in patients taking antipsychotic drugs and we examined studies of antipsychotic-naive patients for comparison purposes.


Fourteen out of 26 longitudinal studies showed a decline in global brain or grey-matter volume or an increase in ventricular or cerebrospinal fluid (CSF) volume during the course of drug treatment, including the largest studies conducted. The frontal lobe was most consistently affected, but overall changes were diffuse. One large study found different degrees of volume loss with different antipsychotics, and another found that volume changes were associated with taking medication compared with taking none. Analyses of linear associations between drug exposure and brain volume changes produced mixed results. Five out of 21 studies of patients who were drug naive, or had only minimal prior treatment, showed some differences from controls in volumes of interest. No global differences were reported in three studies of drug-naive patients with long-term illness. Studies of high-risk groups have not demonstrated differences from controls in global or lobar brain volumes.


Some evidence points towards the possibility that antipsychotic drugs reduce the volume of brain matter and increase ventricular or fluid volume. Antipsychotics may contribute to the genesis of some of the abnormalities usually attributed to schizophrenia.

Corresponding author
*Address for correspondence: Dr J. Moncrieff, Department of Mental Health Sciences, University College London, Charles Bell House, 67-73, Riding House Street, London, WIW7EJ, UK. (Email:
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