title: Randomized crossover study of the histamine H3 inverse agonist MK-0249 for the treatment of cognitive impairment in patients with schizophrenia.
abstract: BACKGROUND
  Current antipsychotic treatments have little impact on the cognitive deficits associated with schizophrenia. It has been proposed that agents which promote histamine release may enhance cognition. We evaluated whether the H3 inverse agonist MK-0249 might improve cognitive deficits in patients with schizophrenia.
  
  
  METHODS
  Outpatients (N=55) with schizophrenia between ages 21 and 55 who were clinically stable, experienced no more than mild to moderate overall symptoms (PANSS score total 36-75), and were taking a stable dose of antipsychotic medication were randomized to MK-0249 10mg and placebo in a multi-center, randomized, double-blind, 2-period (4-weeks per period), cross-over study. The primary efficacy endpoint was the mean change from baseline at 4-weeks of treatment in the total cognitive score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. Other assessments of cognition were also performed.
  
  
  RESULTS
  A total of 46 patients completed the study. MK-0249 10mg did not demonstrate a statistically significant difference compared to placebo in the mean change from baseline in the total cognitive score on the BACS battery after 4-weeks of treatment (-0.1, 95% CI: -2.3, 2.1) or with regard to secondary measures of attention/processing speed, episodic memory, or working memory after 4-weeks of treatment. The incidence of adverse events was greater during the MK-0249 treatment period (25/52 patients, 48.1%) compared to the placebo treatment period (15/51 patients, 29.4%).
  
  
  CONCLUSIONS
  MK-0249 10mg once daily was not superior to placebo in the treatment of cognitive impairment in patients with schizophrenia after 4-weeks. (Clinicaltrials.gov: NCT00506077).
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ 19454, USA. michael.egan@merck.com
authors.forename: Michael
authors.initials: M
authors.lastname: F Egan
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Regina
authors.initials: R
authors.lastname: Gottwald
authors.forename: Lyn
authors.initials: L
authors.lastname: Harper-Mozley
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Duane
authors.initials: D
authors.lastname: Snavely
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.forename: David
authors.initials: D
authors.lastname: Michelson
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D052999:Quinazolinones / Q000627:therapeutic use*; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C574738:MK-0249; D052999:Quinazolinones