Efficacy and Tolerability of Two Novel “Standard of Care” Treatments—Intranasal Esketamine Versus Intravenous Ketamine—for Treatment-Resistant Depression in Naturalistic Clinical Practice: Protocol for a Pilot Observational Study (Preprint)
Bibliographic record
Abstract
BACKGROUND Intravenous (IV) ketamine and intranasal (IN) esketamine have been studied as novel alternatives to manage treatment-resistant depression (TRD). The objective of this observational pilot study is to compare the real-world effectiveness and tolerability of IV ketamine and IN esketamine in the management of unipolar TRD. OBJECTIVE To compare the effectiveness (primary outcome measure) and tolerability (secondary outcome measure) of racemic ketamine and esketamine in the management of TRD in adults and provide an expert qualitative commentary on the application of IV ketamine and IN esketamine in clinical practice (exploratory objective), focusing on the recruitment process, patient retention, effectiveness, and tolerability of the treatments. METHODS This is a multicenter prospective observational study of naturalistic clinical practice. We expect to recruit 10 patients per treatment arm—IV ketamine or IN esketamine per center (2 centers, total 40 subjects). Patients experiencing moderate to severe TRD and who are candidates for receiving low-dose IV ketamine treatments or IN esketamine as part of their standard-of-care treatments will be recruited. We will measure the effectiveness of each treatment arm by measuring the severity of depression symptoms using the Montgomery and Åsberg Depression Rating Scale; tolerability, side effects, and the appearance of dissociation symptoms using the simplified 6-item version of the Clinician Administered Dissociative Symptom Scale (CADSS-6); and potential for abuse using a Likeability and Craving Questionnaire. Logistic regression will examine odds ratios, number needed to treat for response and remission, number needed to harm, and likelihood to be helped or harmed of each treatment. Covariate analysis will assess the impact of site and demographic variables on treatment efficacy. RESULTS This observational trial was approved by the Queen’s University Health Science and Affiliated Teaching Hospital’s Research Ethics Board in February 2021. The two research centers involved have started patient recruitment. Our research center (Providence Care Hospital, Kingston, Ontario) has recruited 9 patients so far. We expect to finalize data gathering by August 2022. The manuscript is expected to be published by December 2022. CONCLUSIONS We hypothesize that both treatments will have comparable rapid and robust antidepressant effects and similar tolerability profiles in a real-world setting for the management of TRD. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/34711
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.030 | 0.033 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.004 | 0.005 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.022 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".