title: ITI-007 for the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind, Controlled Trial.
abstract: An urgent need exists for new treatments of schizophrenia that are effective against a broad range of symptoms and free of limiting safety issues. ITI-007 is a new molecular entity with a pharmacologic profile that combines dose-related monoamine modulation with phosphorylation of intracellular signaling proteins.
  
  
  
  A phase II randomized, double-blind, placebo-controlled, and active-controlled trial was conducted at eight sites in the United States with randomization of 335 acutely psychotic adults with schizophrenia. ITI-007 (60 mg and 120 mg), placebo, and risperidone, included for assay sensitivity, were evaluated as monotherapy for 4 weeks. The primary outcome measure was the Positive and Negative Syndrome Scale total score, with secondary analyses conducted on symptom subscales.
  
  
  
  ITI-007 60 mg (p = .017, effect size = .4) and risperidone (p = .013, effect size = .4) demonstrated antipsychotic efficacy superiority over placebo on the primary end point. The results of secondary analyses reflected improvements in negative and depressive symptoms by ITI-007 60 mg. ITI-007 120 mg did not separate from placebo. However, both doses of ITI-007 were well tolerated in this patient population, as evidenced by low discontinuation and adverse event rates, and were associated with a benign metabolic profile as evidenced by significantly lower levels of prolactin, fasting glucose, total cholesterol, and triglycerides than risperidone.
  
  
  
  The mechanistically novel investigational drug ITI-007 was effective for the treatment of schizophrenia and comparable with placebo on safety measures in this trial. Secondary analyses indicated that ITI-007 improved negative and depression symptoms and might have expanded therapeutic efficacy in comparison with current antipsychotic drugs.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, New York, New York.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.affiliation: Intra-Cellular Therapies, Inc., New York, New York; 3-D Pharmaceutical Consultants, San Diego, California.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Davis
authors.affiliation: Department of Psychiatry, Hofstra North Shore Long Island Jewish School of Medicine, Hempstead; Zucker Hillside Hospital Glen Oaks, New York.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: Department of Psychiatry, New York University Langone Medical Center, New York; Nathan Kline Institute for Psychiatric Research, Orangeburg, New York.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: Department of Psychiatry, Hofstra North Shore Long Island Jewish School of Medicine, Hempstead; Zucker Hillside Hospital Glen Oaks, New York.
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Intra-Cellular Therapies, Inc., New York, New York.
authors.forename: Sharon
authors.initials: S
authors.lastname: Mates
authors.affiliation: Intra-Cellular Therapies, Inc., New York, New York. Electronic address: kvanover@intracellulartherapies.com.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Vanover
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology; D012559:Schizophrenia / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents; D018967:Risperidone
keywords: Antipsychotic; Comorbid depression; Negative symptoms; Positive symptoms; Prosocial factor; Safety