Skip to main content
Journal cover image

A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia.

Publication ,  Journal Article
Buchanan, RW; Keefe, RSE; Lieberman, JA; Barch, DM; Csernansky, JG; Goff, DC; Gold, JM; Green, MF; Jarskog, LF; Javitt, DC; Kimhy, D; Ball, MP ...
Published in: Biol Psychiatry
March 1, 2011

BACKGROUND: In a previous pilot study, MK-0777--a γ-aminobutyric acid (GABA)(A) α2/α3 partial agonist--was reported to improve delayed memory and cognitive measures of prefrontal cortical function in people with schizophrenia. The current study was designed to further examine the efficacy and safety of MK-0777 for the treatment of cognitive impairments in schizophrenia. METHODS: Sixty people with DSM-IV schizophrenia entered a 4-week, multi-center, double-blind, placebo-controlled, randomized clinical trial. Participants were randomized to: MK-0777 3 mg b.i.d. (n = 18); MK-0777 8 mg b.i.d. (n = 21); or placebo (n = 21). Participants were clinically stable. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, AX-Continuous Performance Test, and N-Back were used to assess cognition. The University of California San Diego (UCSD) Performance Based Skills Assessment-2 and the Schizophrenia Cognition Rating Scale assessed functional capacity and served as functional outcome coprimary measures. RESULTS: There were no significant group differences on the primary outcome measure, the MATRICS Consensus Cognitive Battery composite score. Secondary analyses suggested that participants randomized to placebo performed significantly better on visual memory and reasoning/problem-solving tests than participants assigned to either MK-0777 dose. There were no significant group differences on the AX-Continuous Performance Test or N-Back d prime scores or UCSD Performance-Based Skills Assessment-2 and Schizophrenia Cognition Rating Scale total scores. In general, MK-0777 was well-tolerated with minimal side effects. CONCLUSIONS: The study results suggest that MK-0777 has little benefit for cognitive impairments in people with schizophrenia. The GABA(A) receptor remains a promising target, but a more potent partial agonist with greater intrinsic activity at the GABA(A) α2 site might be needed for cognitive enhancement in schizophrenia.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Biol Psychiatry

DOI

EISSN

1873-2402

Publication Date

March 1, 2011

Volume

69

Issue

5

Start / End Page

442 / 449

Location

United States

Related Subject Headings

  • Young Adult
  • Triazoles
  • Treatment Outcome
  • Schizophrenic Psychology
  • Schizophrenia
  • Receptors, GABA-A
  • Pyridazines
  • Psychiatry
  • Psychiatric Status Rating Scales
  • Neuropsychological Tests
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Buchanan, R. W., Keefe, R. S. E., Lieberman, J. A., Barch, D. M., Csernansky, J. G., Goff, D. C., … Marder, S. R. (2011). A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry, 69(5), 442–449. https://doi.org/10.1016/j.biopsych.2010.09.052
Buchanan, Robert W., Richard S. E. Keefe, Jeffrey A. Lieberman, Deanna M. Barch, John G. Csernansky, Donald C. Goff, James M. Gold, et al. “A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia.Biol Psychiatry 69, no. 5 (March 1, 2011): 442–49. https://doi.org/10.1016/j.biopsych.2010.09.052.
Buchanan RW, Keefe RSE, Lieberman JA, Barch DM, Csernansky JG, Goff DC, et al. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry. 2011 Mar 1;69(5):442–9.
Buchanan, Robert W., et al. “A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia.Biol Psychiatry, vol. 69, no. 5, Mar. 2011, pp. 442–49. Pubmed, doi:10.1016/j.biopsych.2010.09.052.
Buchanan RW, Keefe RSE, Lieberman JA, Barch DM, Csernansky JG, Goff DC, Gold JM, Green MF, Jarskog LF, Javitt DC, Kimhy D, Kraus MS, McEvoy JP, Mesholam-Gately RI, Seidman LJ, Ball MP, McMahon RP, Kern RS, Robinson J, Marder SR. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry. 2011 Mar 1;69(5):442–449.
Journal cover image

Published In

Biol Psychiatry

DOI

EISSN

1873-2402

Publication Date

March 1, 2011

Volume

69

Issue

5

Start / End Page

442 / 449

Location

United States

Related Subject Headings

  • Young Adult
  • Triazoles
  • Treatment Outcome
  • Schizophrenic Psychology
  • Schizophrenia
  • Receptors, GABA-A
  • Pyridazines
  • Psychiatry
  • Psychiatric Status Rating Scales
  • Neuropsychological Tests