Neurocognitive effects of ketamine and association with antidepressant response
in individuals with treatment-resistant depression: a randomized controlled
trial.
Author(s): Murrough JW(1), Burdick KE(2), Levitch CF(3), Perez AM(4), Brallier JW(4), Chang
LC(5), Foulkes A(6), Charney DS(7), Mathew SJ(8), Iosifescu DV(1).
Affiliation(s): Author information:
(1)1] Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School
of Medicine at Mount Sinai, New York, NY, USA [2] Fishberg Department of
Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3]
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY,
USA. (2)1] Fishberg Department of Neuroscience, Icahn School of Medicine at Mount
Sinai, New York, NY, USA [2] Friedman Brain Institute, Icahn School of Medicine
at Mount Sinai, New York, NY, USA [3] Department of Psychiatry, Icahn School of
Medicine at Mount Sinai, New York, NY, USA. (3)Mood and Anxiety Disorders
Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New
York, NY, USA. (4)Department of Anesthesiology, Icahn School of Medicine at Mount
Sinai, New York, NY, USA. (5)Department of Anesthesiology, Baylor College of
Medicine, Houston, TX, USA. (6)Menninger Department of Psychiatry and Behavioral
Sciences, Baylor College of Medicine, Houston, TX, USA. (7)1] Mood and Anxiety
Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount
Sinai, New York, NY, USA [2] Fishberg Department of Neuroscience, Icahn School of
Medicine at Mount Sinai, New York, NY, USA [3] Department of Pharmacology and
Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
(8)1] Michael E. Debakey VA Medical Center, Houston, TX, USA [2] Menninger
Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine,
Houston, TX, USA.
Publication date & source: 2015, Neuropsychopharmacology. , 40(5):1084-90
The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays
rapid antidepressant effects in patients with treatment-resistant depression
(TRD); however, the potential for adverse neurocognitive effects in this
population has not received adequate study. The current study was designed to
investigate the delayed neurocognitive impact of ketamine in TRD and examine
baseline antidepressant response predictors in the context of a randomized
controlled trial. In the current study, 62 patients (mean age = 46.2 ± 12.2) with
TRD free of concomitant antidepressant medication underwent neurocognitive
assessments using components of the MATRICS Consensus Cognitive Battery (MCCB)
before and after a single intravenous infusion of ketamine (0.5 mg/kg) or
midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in
a 2:1 fashion under double-blind conditions and underwent depression symptom
assessments at 24, 48, 72 h, and 7 days post treatment using the
Montgomery-Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive
assessment was conducted once at 7 days. Neurocognitive performance improved
following the treatment regardless of treatment condition. There was no
differential effect of treatment on neurocognitive performance and no association
with antidepressant response. Slower processing speed at baseline uniquely
predicted greater improvement in depression at 24 h following ketamine (t = 2.3,
p = 0.027), while controlling for age, depression severity, and performance on
other neurocognitive domains. In the current study, we found that ketamine was
devoid of adverse neurocognitive effects at 7 days post treatment and that slower
baseline processing speed was associated with greater antidepressant response.
Future studies are required to further define the neurocognitive profile of
ketamine in clinical samples and to identify clinically useful response
moderators.
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