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No negative symptoms in healthy volunteers after single doses of amisulpride, aripiprazole, and haloperidol: a double-blind placebo-controlled trial

Park, Chul-Hyuna; Park, Tae-Wona,b; Yang, Jong-Chula,b; Lee, Keon-Hakd; Huang, Guang-Biaoa,b; Tong, Zhaoa,b; Park, Myung-Sookc; Chung, Young-Chula,b

International Clinical Psychopharmacology: March 2012 - Volume 27 - Issue 2 - p 114–120
doi: 10.1097/YIC.0b013e3283502773
Original Articles

Noncompliance and poor outcome in patients with schizophrenia are closely related to the negative symptoms secondary to antipsychotics. No controlled study has evaluated whether amisulpride and aripiprazole induce negative symptoms. The aim of this study was to assess the effects of single doses of amisulpride, aripiprazole, haloperidol, and risperidone in healthy volunteers. Seventy-eight young volunteers took part in this double-blind, randomized, placebo-controlled, parallel study of four antipsychotics: 400 mg amisulpride, 10 mg aripiprazole, 3 mg haloperidol, and 2 mg risperidone. Assessments of negative symptoms were done 4 h after administration using both subjective rating scales (Neuroleptic Induced Deficit Syndrome Scale and Subjective Deficit Syndrome Scale) and an objective rating scale (Scale for the Assessment of Negative Symptoms). Risperidone only produced significant increases on the avolition score of the Neuroleptic Induced Deficit Syndrome Scale and blunted affect and alogia scores of the Scale for the Assessment of Negative Symptoms compared with placebo. The effect on blunted affect persisted after controlling for mental sedation. Amisulpride, aripiprazole, and haloperidol did not induce negative symptoms. Aripiprazole and risperidone induced mild extrapyramidal symptoms. The most common adverse events were somnolence and cognitive slowing. These data indicate that a single risperidone dose induces negative symptoms in normal volunteers, whereas amisulpride, aripiprazole, and haloperidol do not. These characteristics of antipsychotics should be considered when choosing optimal drugs for patients with psychosis.

aDepartment of Psychiatry, Chonbuk National University Medical School and Institute for Medical Science

bDepartment of Psychiatry, Chonbuk National University Hospital & Research Institute of Clinical Medicine

cDepartment of Psychology, Chonbuk National University Graduate School, Jeonju

dMaemsarang Hospital, In-san Medical Foundation, Wanju, Korea

Correspondence to Young-Chul Chung, MD, PhD, Department of Psychiatry, Chonbuk National University Medical School, Keumam Dong 634-18, Jeonju 561-712, Korea Tel: +82 63 250 2185; fax: +82 63 275 3157; e-mail:

Received June 20, 2011

Accepted December 7, 2011

© 2012 Lippincott Williams & Wilkins, Inc.