Anxiety during ketamine infusions is associated with negative treatment responses in major depressive disorder.
Sabine Aust, Matti Gärtner, Laura Basso, Christian Otte, Katja Wingenfeld, Woo Ri Chae, Isabella Heuser-Collier, Francesca Regen, Nicoleta Carmen Cosma, Franziska Van Hall, Simone Grimm, Malek Bajbouj
European Neuropsychopharmacology April 2019 DOI: 10.1016/j.euroneuro.2019.02.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 31 |
| Population | Patients with treatment-resistant major depressive disorder (mean age 49.5 years, 16 women) |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg over 40 min, three infusions per week |
| Duration | Two consecutive weeks of infusions (six infusions total); assessments at baseline, 4 and 24 hours, and end of treatment |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS), 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) |
| Topics | Altered states of consciousness Anxiety Depression Ketamine Esketamine |
| Keywords | Subjective experiences |
| Key findings | Ketamine produced a response in 55% of patients (17 of 31) after six infusions, while 45% (14 of 31) did not respond. Anxiety-related experiences during the first infusion were higher in non-responders, and both early MADRS reduction and ketamine-induced anxiety predicted end-of-treatment response. The authors argue these subjective experiences may serve as a phenotypic response predictor. |
Abstract
About 20 to 30 percent of patients with Major Depressive Disorder (MDD) do not respond to standard treatment and are considered treatment-resistant. The N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in treatment-resistant MDD, but it is unknown whether its acute psychological effects are related to the later antidepressant effect. Therefore, we investigated the association between antidepressant responses to ketamine and the quality of ketamine-induced psychological experiences in MDD. A total of 31 patients (M = 49.5 ± 11.2 years, 16 women) were treated with three ketamine infusions per week (0.5 mg/ kg over 40 min) administered for two consecutive weeks. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after four and 24 h and at end of treatment. The 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) was applied four hours after the first infusion to assess the subjective quality of acute psychological effects. Patients with a ≥ 50% MADRS reduction from baseline to end of treatment were considered as responders. After six infusions, 17 of 31 patients (55%) showed a response to ketamine treatment, while 14 patients (45%) had no response. Anxiety-related experiences induced by ketamine were significantly higher in non-responders. Percentage MADRS reduction after four hours and individual levels of ketamine-induced anxiety were predictive of a response at end of treatment. The study demonstrated the considerable impact of ketamine-induced anxiety on the antidepressant efficacy of ketamine. It underpins the importance of considering patients' subjective experiences and underlines the possibility of a phenotypic response predictor.
Comparable studies
Other observational and cohort studies on ketamine for anxiety, most cited first.
Citations in the library
Cited by 51
- Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review Frontiers in Psychiatry July 12, 2022
- Reviewing the Potential of Psychedelics for the Treatment of PTSD The International Journal of Neuropsychopharmacology March 12, 2020
- Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants The International Journal of Neuropsychopharmacology November 16, 2020
- Therapeutic effect of an ayahuasca analogue in clinically depressed patients: a longitudinal observational study. Psychopharmacology January 24, 2022
- A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. Journal of Affective Disorders 2022
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Cites 19
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- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
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