The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial
Notice bibliographique
Résumé
BACKGROUND: Major depressive disorder is among the most disabling illnesses worldwide, with a lifetime prevalence of 16.2%. Research suggests that 20% to 40% of patients with depression do not respond to pharmacotherapy, developing treatment-resistant depression. Electroconvulsive therapy is the gold standard for treating individuals with treatment-resistant depression, with remission rates of approximately 75% to 90%. However, 10% to 25% of patients do not respond to electroconvulsive therapy, and many are unable to tolerate it due to the side effects. Both groups are considered to be patients who do not respond to electroconvulsive therapy, because both groups continue to exhibit symptoms of severe depression, have a limited number of treatment options available, and are in need of rapid treatment. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been shown to exert rapid antidepressant effects in patients with treatment-resistant depression when administered in subanesthetic doses through 40-minute intravenous infusions. Recently, a ketamine compound, esketamine (Spravato), that is administered through the intranasal route received regulatory approval by the US Food and Drug Administration and Health Canada to treat depression. However, esketamine is challenging to access due to high costs and limited availability. Racemic ketamine (rketamine) is cheap and easy to access; however, the effects in patients who have not responded to electroconvulsive therapy have yet to be understood or tested. This study will use transcranial magnetic stimulation to study mechanisms of human brain cortical physiology at the systemic level to identify neurobiomarkers of response. OBJECTIVE: The objective of this open-label pilot clinical trial is to test the feasibility and safety of intranasal ketamine in patients who have not responded to electroconvulsive therapy. The primary outcome is to determine the feasibility of a larger randomized controlled trial to test the efficacy of intranasal ketamine for patients who have not responded to electroconvulsive therapy for clinical indicators in unipolar depression. The secondary outcome is to determine the preliminary effects of an intervention on clinical outcomes, such as depressive symptoms, suicidal ideation, and quality of living. The third outcome is to explore neurophysiological changes as measured by transcranial magnetic stimulation electromyography and electroencephalography to measure changes in cortical excitability as potential predictors of clinical response. METHODS: A sterile solution of racemic ketamine hydrochloride will be administered twice per week for 4 weeks (8 sessions) intranasally to patients with treatment-resistant depression who did not respond to or could not tolerate an acute course of electroconvulsive therapy. We will recruit 25 adults (24-65 years old) over the course of 2 years from an academic psychiatric hospital in Toronto, Canada. RESULTS: This study has received ethics approval, and funding has been secured. The study is currently active. CONCLUSIONS: This is the first study to test repeated doses of intranasal rketamine in patients who have not responded to electroconvulsive therapy for depression. Results from this study will (1) inform the development of a larger adequately powered randomized controlled trial to test the efficacy of intranasal ketamine for depression and (2) determine potential neurophysiological markers of clinical response. TRIAL REGISTRATION: Clinical Trials.gov NCT05137938; http://clinicaltrials.gov/ct2/show/NCT05137938. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30163.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,014 | 0,013 |
| Méta-épidémiologie (sens strict) | 0,005 | 0,002 |
| Méta-épidémiologie (sens large) | 0,008 | 0,004 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,003 | 0,003 |
| Communication savante | 0,003 | 0,003 |
| Science ouverte | 0,004 | 0,002 |
| Intégrité de la recherche | 0,006 | 0,008 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,049 | 0,011 |
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 ».