Effect of intravenous ketamine on sleep, cognition and anxiety in patients with treatment-resistant depression
Notice bibliographique
Résumé
Objective: Multiple controlled trials have demonstrated the short-term effectiveness of single or serial administration of low-dose IV ketamine, a potent noncompetitive NMDA antagonist, for treating the symptoms of depression in patients with major depression (MDD) and bipolar depression (BD) who failed to respond to multiple trials of pharmacotherapy and, in some cases, electroconvulsive therapy.Most impressively, remission rates at over 50% exceeded what is seen with any other medication treatment.Positive benefit from ketamine persisted for 3-14 days on average following a single infusion and for 18-19 days following serial infusions administered over 12-14 days.While these trials have focused on overall symptom reduction, additional research has shown both single IV ketamine infusions as well as multiple infusions can significantly reduce suicidal ideation, with some anti-suicidal effects separate from direct effects of improved mood.Thus, IV ketamine promises to be a important treatment for mood disorder; the question is, can we identify predictors of response?In addition to clinical predictors, are there blood-based biomarkers of response?We conducted a clinical trial ("Bio-K") using IV ketamine for treatment-resistant depression to identify biomarkers linked to remission.Here, we report the clinical efficacy and side effect outcomes.Methods: Across 4 US sites, 75 patients ages 18 -65 with treatment-refractory unipolar or bipolar depression received 3 IV ketamine infusions over an 11-day period.Key exclusion criteria were psychotic symptoms, significant substance abuse, unstable medical conditions, and any use of cannabis.Pre-existing antidepressant medication was maintained.Primary outcome was remission as measured by Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcome of 50% reduction in Beck Suicide Scale score.Safety monitoring and varying durations of infusions were also key parameters.Results: Using remission as MADRS score less than 9, after 3 infusions 52% achieved remission.Most participants had significant suicidal ideation at baseline; of these, two-thirds (67%) experienced at least a 50% reduction in suicidality.Side effects were minimal.Uniquely, we had three different types of infusion durations, with slow (100-minute) or regular (40-minute) infusions showing comparable safety and efficacy.Exploration of clinical factors revealed no link between BMI, age, or gender to remission.Conclusions: Our limitations included a lack of a control group, necessitating caution about conclusions of efficacy balanced by the utility of reporting "realworld" outcomes across multiple clinical sites.We could also not separately analyze results for bipolar disorder due to small numbers.Nevertheless, the consistency of outcomes across clinical sites and across multiple instruments, suggests high efficacy and safety of IV ketamine for serious depressive episodes.Our data on varying ketamine infusion duration adds novel insights into the clinical administration of this new treatment for refractory and severe patients.Together, the Bio-K clinical results are promising and provides significant sample sizes for forthcoming biological markers analyses.Trial Registration: ClinicalTrials.gov: NCT03156504
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».