Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review.

Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary reports indicate that it may be beneficial for depressed patients reporting symptoms of anhedonia. In this systematic review we aim to assess and analyze the existing body of evidence regarding the therapeutic effects of ketamine on the domain of anhedonia. Electronic databases (PubMed, APA Psycinfo and Web of Science) were searched from inception to November 2023. Protocol was registered in PROSPERO under the identifier CRD42023476603. A total of twenty-two studies, including four randomized-controlled trials and eighteen open-label trials were included. All studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, regardless of the number of infusions. Several important limitations were included, first and foremost low number of placebo-controlled randomized-controlled trials. This review indicates a potential anti-anhedonic effect of ketamine in patients with depression. Several trials used neuroimaging techniques which confirm ketamine's effect on functional connectivity correlating with the improvement in anhedonia. Despite considerable variations in methodology and the specific brain regions investigated, these studies collectively point towards ketamine's neuroplastic effects in mitigating anhedonia.
Competing Interests: Declaration of competing interest Julia Kwaśna has no conflict of interest. Aleksander Kwaśny has received research support from GH Research, MSD, Novartis Alina Wilkowska has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen-Cilag, Lundbeck, Polpharma, Sanofi, and Valeant. Joanna Szarmach has received research support from KCR, Janssen, Otsuka, Apodemus, Novartis, Cortexyme, GH Research and Acadia. Jakub Słupski has received research support from Actavis, Eli Lilly, Minerva, Sunovion, Celon, Janssen, Biogen, Novartis, HMNC Brain Health. Adam Włodarczyk has received research support from KCR, Janssen, Otsuka, Apodemus, Novartis, Cortexyme, GH Research and Acadia. Wiesław Jerzy Cubała has received grants from Acadia, Angelini, Celon, Cortexyme, GH Research, HMNC Brain Health, IntraCellular Therapies, Janssen, MSD, Novartis, Otsuka. He has albo received honoraria from Angelini, Celon, Janssen, Novartis, Sanofi. He is a member of advisory boards in Angelini, Celon (terminated), Douglas Pharmaceuticals, Janssen, MSD, Novartis, Sanofi.
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