Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression

Lally, N; Nugent, A C; Luckenbaugh, D A; Ameli, R; Roiser, J P; Zarate, C A

doi:10.1038/tp.2014.105

Cited by 271Treatment of Major DepressionBipolar Disorder and TreatmentElectroconvulsive Therapy Studies

Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression

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Lally, N, Nugent, A C, Luckenbaugh, D A, Ameli, R, Roiser, J P, Zarate, C A·2014·Translational Psychiatry

DOI 10.1038/tp.2014.105PMC PMC4350513

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Abstract

Anhedonia--which is defined as diminished pleasure from, or interest in, previously rewarding activities-is one of two cardinal symptoms of a major depressive episode. However, evidence suggests that standard treatments for depression do little to alleviate the symptoms of anhedonia and may cause reward blunting. Indeed, no therapeutics are currently approved for the treatment of anhedonia. Notably, over half of patients diagnosed with bipolar disorder experience significant levels of anhedonia during a depressive episode. Recent research into novel and rapid-acting therapeutics for depression, particularly the noncompetitive N-Methyl-D-aspartate receptor antagonist ketamine, has highlighted the role of the glutamatergic system in the treatment of depression; however, it is unknown whether ketamine specifically improves anhedonic symptoms. The present study used a randomized, placebo-controlled, double-blind crossover design to examine whether a single ketamine infusion could reduce anhedonia levels in 36 patients with treatment-resistant bipolar depression. The study also used positron emission tomography imaging in a subset of patients to explore the neurobiological mechanisms underpinning ketamine's anti-anhedonic effects. We found that ketamine rapidly reduced the levels of anhedonia. Furthermore, this reduction occurred independently from reductions in general depressive symptoms. Anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen. Our study emphasizes the importance of the glutamatergic system in treatment-refractory bipolar depression, particularly in the treatment of symptoms such as anhedonia.

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Depression is associated with deficits in reward motivation to a greater extent than consummatory aspects of reward.
“It was suggested that depression is associated with deficits in reward motivation to a greater extent than consummatory aspects of reward (Chentsova-Dutton and Hanley, 2010; Lally et al., 2014).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Lally et al., 2014
Ketamine rapidly reduces anhedonia.
“and to rapidly reduce anhedonia 25–27.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [27]

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17.3 Intravenous Ketamine for Treatment-Resistant Depression in Adolescents?
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Authors: Lally, N., Nugent, A. C., Luckenbaugh, D. A., Ameli, R., Roiser, J. P., & Zarate, C. A.
Affiliations: National Institutes of Health (US)
University College London (GB)
Corresponding author: Lally, N
ORCID: Lally, N
Nugent, A C
Ameli, R
Roiser, J P
Zarate, C A
Venue: Translational Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2014-10-14
Volume: 4
Issue: 10
Pages: e469-e469
ISSN: 2158-3188 (ISSN-L)
DOI: 10.1038/tp.2014.105
PMC: PMC4350513
OpenAlex: W2005846380
Cited by: 271
References: 89
Citations by year: 2026: 12 · 2025: 23 · 2024: 20 · 2023: 25 · 2022: 33 · 2021: 24 · 2020: 25 · 2019: 29 · 2018: 23 · 2017: 13 · 2016: 20 · 2015: 23 · 2014: 1
FWCI: 13.82
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/3.0/ (tdm)
creativecommons.org/licenses/by-nc-sa/3.0/ (vor)
Locations: Translational Psychiatry (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: National Alliance for Research on Schizophrenia and Depression
Wellcome Trust (WT095465)
National Institutes of Health (04-M-0222)
U.S. Public Health Service (04-M-0222)
National Institute of Mental Health (04-M-0222)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords: ketamine, anhedonia, bipolar depression, treatment-resistant depression, NMDA receptor antagonists, glutamatergic system, dorsal anterior cingulate cortex, putamen, glucose metabolism, rapid-acting antidepressants, reward processing
MeSH terms: Adolescent, Adult, Aged, Bipolar Disorder, Brain, Double-Blind Method, Female, Humans, Ketamine, Male, Middle Aged, Treatment Outcome, Cross-Over Studies, Excitatory Amino Acid Antagonists, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography, Young Adult, Anhedonia, Depressive Disorder, Treatment-Resistant

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Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression

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