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Alternative pharmacologic targets for the treatment of schizophrenia: results from phase I and II trials

Miyamoto, Seiyaa; Jarskog, Lars F.b,c; Fleischhacker, W. Wolfgangd

Current Opinion in Psychiatry: March 2013 - Volume 26 - Issue 2 - p 158–165
doi: 10.1097/YCO.0b013e32835d8296
SCHIZOPHRENIA AND RELATED DISORDERS: Edited by W. Wolfgang Fleischhacker and Lynn E. DeLisi

Purpose of review The current article provides a brief review of the clinical efficacy and safety outcomes from selected phase I and II clinical trials of compounds in development acting on targets beyond the dopamine D2 receptor in patients with schizophrenia.

Recent findings A number of experimental pharmacological targets have been studied in clinical trials. Among those, glutamatergic and nicotinergic pathways have received most attention. Glycine transporter 1 inhibitors used adjunctively with antipsychotics suggest efficacy for negative symptoms of schizophrenia. Adjunctive alpha7 nicotinic acetylcholine receptor agonists and minocycline may improve negative symptoms and cognitive deficits. Adjunctive oxytocin may benefit psychotic symptoms and social cognitive deficits. Adjunctive erythropoietin may improve cognitive function.

Summary Experimental therapeutic research for schizophrenia is rapidly expanding and a number of compounds with novel mechanisms of action are demonstrating encouraging evidence for efficacy across a range of symptoms. However, much work still needs to be conducted before these new agents can be considered for routine clinical treatment. In particular, further assessment of efficacy and longer term safety and tolerability monitoring are required.

aDepartment of Neuropsychiatry, St Marianna University School of Medicine, Kawasaki, Japan

bDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill

cNorth Carolina Psychiatric Research Center, Central Regional Hospital, Raleigh Campus, Raleigh, North Carolina, USA

dDepartment of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria

Correspondence to Seiya Miyamoto, MD, PhD, Associate Professor, Director of Schizophrenia Treatment Center, Department of Neuropsychiatry, St Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. Tel: +81 44 977 8111; fax: +81 44 976 3341; e-mail:

© 2013 Lippincott Williams & Wilkins, Inc.