Evidence map›Paper›PMID 21145041›Full record

Trial reportBiological psychiatry2011

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

Robert W Buchanan, Richard S E Keefe, Jeffrey A Lieberman, Deanna M Barch, John G Csernansky, Donald C Goff, James M Gold, Michael F Green, L Fredrik Jarskog, Daniel C Javitt and 10 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Biological psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 3 pooled it
6.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 3 syntheses or guidelines pooled it, 170 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.The Cochrane database of systematic reviews · 2022
    Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015
    Trial
  8. A randomized, placebo-controlled study investigating the nicotinic α7 agonist, RG3487, for cognitive deficits in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014
    Trial
  9. Trial
  10. Trial
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Neurobiology of schizophrenia.Current opinion in neurobiology · 2024
    Review
  17. Review
  18. Review
  19. Modulators of GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Review
  20. Review

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 11 institutions in 1 country.

Robert W BuchananMaryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Maple & Locust Streets, Baltimore, MD 21228, USA. rwbuchanan@mprc.umaryland.edu
Richard S E Keefe
Jeffrey A Lieberman
Deanna M Barch
John G Csernansky
Donald C Goff
James M Gold
Michael F Green
L Fredrik Jarskog
Daniel C Javitt
David Kimhy
Michael S Kraus
Joseph P McEvoy
Raquelle I Mesholam-Gately
Larry J Seidman
M Patricia Ball
Robert P McMahon
Robert S Kern
James Robinson
Stephen R Marder
University of Maryland, Baltimore · USVA Desert Pacific Healthcare Network · USDuke Medical Center · USHarvard University · USNew York Psychoanalytic Society and Institute · USNew York University · USColumbia University · USDuke University Hospital · USMassachusetts General Hospital · USNorthwestern University · USWashington University in St. Louis · US

Funding

New Treatment and Mechanisms in SchizophreniaK24MH002025 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI GOFF, DONALD C. · 2001 to 2011
$1.6M
TREATMENT UNITS FOR RESEARCH ON NEUROCOGNITION AND SCHIZOPHRENIA /TURN-278041003N01MH041003 · NIMH · UNIVERSITY OF CALIFORNIA . LOS ANGELES · PI MARDER, STEPHEN R · 2004 to 2006
–
NIMH NIH HHS K24 MH002025NIMH NIH HHS N01 MH041003
6 · The paper itself

Abstract

backgroundIn 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.

methodsSixty 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.

resultsThere 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.

conclusionsThe 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.

Indexed as

Schizophrenic PsychologyAdolescentAdultCognitionCognition DisordersDiagnostic and Statistical Manual of Mental DisordersDouble-Blind MethodFemaleGABA AgonistsHumansMaleMiddle AgedNeuropsychological TestsPsychiatric Status Rating ScalesPyridazinesReceptors, GABA-A7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo(4,3-b)pyridazineGABA AgonistsGABRA2 protein, humanPyridazinesReceptors, GABA-ATriazoles

Identifiers

PMID21145041
PMCPMC3058394
OpenAlexW2136125607

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.