Psychiatry research · 2026
Faster and greater antidepressant response to intravenous ketamine in bipolar compared with unipolar treatment-resistant depression: Diagnostic and sex-related findings from a naturalistic study.
СтатьяНаблюдательное исследованиеСравнительное исследованиеНазвание и аннотация: Перевод в очереди
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Carmellini Pietro, Fagiolini Andrea, Pinzi Mario, Magno Marta, Martella Donato, Nicchi Lorenzo, Rescalli Maria Beatrice, Tarantino Francesca, Tinturini Rebecca, Scheggi Simona, Gualtieri Giacomo, Cuomo Alessandro
Аннотация
BACKGROUND: Intravenous ketamine has emerged as a rapid-acting antidepressant intervention that has shown promising effects in patients with treatment-resistant depression, although evidence remains heterogeneous and less well established across diagnostic subtypes. Nevertheless, real-world data comparing diagnostic subtypes and sex-related differences remain limited. This observational study examined the antidepressant efficacy, tolerability, and dissociative effects of intravenous ketamine in patients with treatment-resistant unipolar depression (TRD) and treatment-resistant bipolar depression (TRBD) in a naturalistic clinical setting.
METHODS: Ninety-seven adult patients meeting DSM-5 criteria for unipolar or bipolar depression received racemic intravenous ketamine at a university psychiatric center. Depressive symptoms and global clinical severity were assessed at baseline and up to three months using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression-Severity scale (CGI-S). Dissociative symptoms were measured with the Clinician-Administered Dissociative States Scale (CADSS). Longitudinal outcomes were analyzed using mixed-effects models.
RESULTS: Both groups experienced significant reductions in depressive symptoms over time. Patients with bipolar depression demonstrated a faster and greater improvement than those with unipolar depression, with differences emerging from week 2 and persisting through three months. CGI-S scores showed a comparable pattern. The dissociative symptoms showed no change throughout the study and they appeared at the same level in all diagnostic categories. Sex-stratified analyses revealed no differences in antidepressant efficacy, although women with unipolar depression exhibited higher dissociative symptoms at three months.
CONCLUSIONS: Intravenous ketamine is effective in real-world treatment-resistant depression, with superior and more sustained antidepressant effects in bipolar compared with unipolar depression.
METHODS: Ninety-seven adult patients meeting DSM-5 criteria for unipolar or bipolar depression received racemic intravenous ketamine at a university psychiatric center. Depressive symptoms and global clinical severity were assessed at baseline and up to three months using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression-Severity scale (CGI-S). Dissociative symptoms were measured with the Clinician-Administered Dissociative States Scale (CADSS). Longitudinal outcomes were analyzed using mixed-effects models.
RESULTS: Both groups experienced significant reductions in depressive symptoms over time. Patients with bipolar depression demonstrated a faster and greater improvement than those with unipolar depression, with differences emerging from week 2 and persisting through three months. CGI-S scores showed a comparable pattern. The dissociative symptoms showed no change throughout the study and they appeared at the same level in all diagnostic categories. Sex-stratified analyses revealed no differences in antidepressant efficacy, although women with unipolar depression exhibited higher dissociative symptoms at three months.
CONCLUSIONS: Intravenous ketamine is effective in real-world treatment-resistant depression, with superior and more sustained antidepressant effects in bipolar compared with unipolar depression.