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Unmet Needs in the Treatment of Schizophrenia: New Targets to Help Different Symptom Domains

J Clin Psychiatry 2014;75(suppl 1):21-26

Current treatments for schizophrenia, although effective for positive symptoms, have not proven as effective for negative symptoms and cognitive dysfunction. Additional strategies, such as combining antipsychotics or adding adjunctive agents to antipsychotics, have also yielded disappointing results in both negative and cognitive symptom domains. However, the N-methyl-d-aspartate (NMDA) receptor hypofunction hypothesis, with its focus on the glutamate system’s effect on dopamine, can explain the positive, negative, and cognitive symptoms in schizophrenia. Therapeutic targets are being explored that focus on NMDA receptors (eg, glycine, d-serine), glycine reuptake inhibition (such as sarcosine and bitopertin), and, through a different pathway, α-7 nicotinic acetylcholine receptor agonism (eg, encenicline).

From the Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY.

This article is derived from the planning teleconference series “Measurement-Based Strategies to Assess and Manage Schizophrenia,” which was held in August 2013 and supported by an educational grant from Genentech.

Dr Citrome is a consultant for Alexza, Alkermes, Bristol-Myers Squibb, Eli Lilly, Envivo, Forest, Genentech, Janssen, Lundbeck, Merck, Mylan, Novartis, Noven, Otsuka, Pfizer, Reviva, Reckitt Benckiser, Sunovion, and Takeda; is a member of the speakers/advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest, Merck, Novartis, Otsuka, Pfizer, Sunovion, and Takeda; and is a stock shareholder of Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, and Pfizer.

Corresponding author: Leslie Citrome, MD, MPH, 11 Medical Park Drive, Ste 106, Pomona, NY 10970 (