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Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism

Overview of attention for article published in American Journal of Psychiatry, August 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#8 of 5,714)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

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Title
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism
Published in
American Journal of Psychiatry, August 2018
DOI 10.1176/appi.ajp.2018.18020138
Pubmed ID
Authors

Nolan R. Williams, Boris D. Heifets, Christine Blasey, Keith Sudheimer, Jaspreet Pannu, Heather Pankow, Jessica Hawkins, Justin Birnbaum, David M. Lyons, Carolyn I. Rodriguez, Alan F. Schatzberg

Abstract

In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects. In a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0.5 mg/kg of ketamine. Response was defined as a reduction ≥50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D) score on postinfusion day 1. In the interim analysis, seven of 12 adults with treatment-resistant depression met the response criterion during the ketamine plus placebo condition. Reductions in 6-item and 17-item HAM-D scores among participants in the ketamine plus naltrexone condition were significantly lower than those of participants in the ketamine plus placebo condition on postinfusion days 1 and 3. Secondary analysis of all participants who completed the placebo and naltrexone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis. The findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 3 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 3 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 1 33%
Unspecified 1 33%
Student > Master 1 33%
Readers by discipline Count As %
Unspecified 1 33%
Pharmacology, Toxicology and Pharmaceutical Science 1 33%
Psychology 1 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 868. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 March 2019.
All research outputs
#4,633
of 12,689,901 outputs
Outputs from American Journal of Psychiatry
#8
of 5,714 outputs
Outputs of similar age
#248
of 271,196 outputs
Outputs of similar age from American Journal of Psychiatry
#1
of 58 outputs
Altmetric has tracked 12,689,901 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,714 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.2. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 271,196 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 58 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.