Effect of intravenous ketamine on sleep, cognition and anxiety in patients with treatment-resistant depression
Bibliographic record
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".