Clin Psychopharmacol Neurosci 2019; 17(2): 250-260  
Effects of Amisulpride Adjunctive Therapy on Working Memory and Brain Metabolism in the Frontal Cortex of Patients with Schizophrenia: A Preliminary Positron Emission Tomography/Computerized Tomography Investigation
Jeong Ha Park1,*, Ji Son Hong1,*, Sun Mi Kim1, Kyung Joon Min1, Un Sun Chung2, Doug Hyun Han1
1Department of Psychiatry, Chung-Ang University Hospital, Seoul, 2Department of Psychiatry, Kyungpook National University Children’s Hospital, Daegu, Korea
Correspondence to: Doug Hyun Han, MD, PhD, Department of Psychiatry, Chung-Ang University Hospital, 102 Heukseok-ro, Dongjack-gu, Seoul 06973, Korea
Tel: +82-2-6299-3132, Fax: +82-2-6299-1114, E-mail:
*These authors contributed equally to this study as co-first authors.
Received: May 31, 2018; Revised: October 7, 2018; Accepted: October 25, 2018; Published online: May 31, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective: Dopamine plays a significant role in working memory by acting as a key neuromodulator between brain networks. Additionally, treatment of patients with schizophrenia using amisulpride, a pure dopamine class 2/3 receptor antagonist, improves their clinical symptoms with fewer side effects. We hypothesized that patients with schizophrenia treated with amisulpride and aripiprazole show increased working memory and glucose metabolism compared with those treated with cognitive behavioral therapy (CBT) and aripiprazole instead.
Methods: Sixteen patients with schizophrenia (eight in the amisulpride group [aripiprazole+amisulpride] and eight in the CBT group [aripiprazole+CBT]) and 15 age- and sex-matched healthy control subjects were recruited for a 12-week-long prospective trial. An [18F]-fluorodeoxyglucose-positron emission tomography/computerized tomography scanner was used to acquire the images.
Results: After 12 weeks of treatment, the amisulpride group showed greater improvement in the Letter-Number Span scores than the CBT group. Additionally, although brain metabolism in the left middle frontal gyrus, left occipital lingual gyrus, and right inferior parietal lobe was increased in all patients with schizophrenia, the amisulpride group exhibited a greater increase in metabolism in both the right superior frontal gyrus and right frontal precentral gyrus than the CBT group.
Conclusion: This study suggests that a small dose of amisulpride improves the general psychopathology, working memory performance, and brain glucose metabolism of patients with schizophrenia treated with aripiprazole.
Keywords: Schizophrenia; Sulpiride; Cognition; Positron-emission tomography.

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