L Encéphale
November 12, 2020
Hugo Bottemanne, A. Claret, Philippe Fossati
10 citations
The long-standing hypothesis that depression stems from a deficiency in monoamines (serotonin, norepinephrine, dopamine) has guided antidepressant development, but conventional treatments targeting these systems have limitations. The success of ketamine has revived interest in other substances, including the hallucinogen psilocybin (which targets serotonin 5HT2A receptors) and the neurosteroid brexanolone (a GABA-A receptor modulator). Unlike standard antidepressants, these modulators of glutamatergic, serotonergic, and GABAergic systems produce rapid antidepressant effects within 24 hours to a week. Beyond the search for a "miracle" molecule, these new targets may help identify biomarkers for rapid-acting antidepressants and reshape treatment strategies for mood disorders.
Hugo Bottemanne, Orphée Morlaàs, Anne Claret et al.
4 citations
preprint
Ketamine infusion makes people with treatment-resistant depression more optimistic about the future by changing how they learn from good and bad news. After a single infusion, patients updated their beliefs more after favorable information and less after unfavorable information, compared to healthy controls. This shift toward optimism was driven by learning more from positive surprises than negative ones. This change in belief-updating predicted early clinical improvement at one week, seen in 19% of patients. The findings suggest ketamine's antidepressant effects involve altering cognitive biases, which could enhance psychotherapy for depression.
medRxiv Preprint Server
April 23, 2026
Willys Cantenys, Zeynep Yoldas, Luc Masset et al.
preprint
Ketamine works quickly as an antidepressant but also causes temporary dissociative symptoms. In everyday clinical settings, it is unclear how much of the antidepressant effect comes from patients' expectations versus from the dissociative experience itself, and how these factors relate to changes in depression over time.