Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Intranasal esketamine has been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior. The authors conducted a systematic review meta-analysis of the available data on its efficacy against depression suicidality well side effects. MEDLINE was searched keyword "esketamine" March 24, 2024, using PRISMA method. Data processing statistical analysis were performed R, version 4.3.3, METAFOR package. Of 1,115 articles initially identified, 87 included discussion. At weeks 2-4, randomized controlled trials mostly negative or failed; however, returned weak but significant positive effect (effect size range, 0.15-0.23 at 2-4), similar to augmentation strategies atypical antipsychotics depression. concerning not any time point. sensitivity produced same results. study findings suggest that esketamine's add-on antidepressants is modest in (similar antipsychotics) absent itself. These need be considered light abuse potential fact long-term effects are still fully known. Some alarming signs deaths emerging during testing phase discussed, along other regulatory issues.

Language: Английский

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Fine-tuning of dopamine receptor signaling with aripiprazole counteracts ketamine’s dissociative action, but not its antidepressant effect

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 8, 2025

Ketamine, a rapid-acting antidepressant, has undesirable psychotomimetic effects, including dissociative effect. There is currently no effective strategy to suppress these side effects while preserving its antidepressant Here, we investigated the of D2/D3 receptor antagonist and partial agonists on ketamine in mice humans. Aripiprazole, agonist, attenuated effect, but maintaining even enhancing antidepressant-like effect forced swim test, whereas raclopride, an antagonist, suppressed both mice. Brain-wide Fos mapping network analysis suggested ventral tegmental area (VTA) as critical region for distinguishing aripiprazole raclopride. In chronic stress model, local infusion raclopride into VTA inhibited ketamine's accompanied by activation dopaminergic neurons, suggesting inhibitory ketamine. Consistently, systemic injections brexpiprazole, agonist similar closer (lower Emax), activated neurons model when co-administered with ketamine, didn't. line results, single-arm, double-blinded clinical study sequential treatments depressed patients (N = 9), co-administration 12 mg symptoms induced effects. Together, findings suggest that fine-tuning dopamine signaling allows selective suppression ketamine-induced dissociation combined use may be preferred therapy treatment-resistant depression.

Language: Английский

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Facts and myths about use of esketamine for treatment-resistant depression: a narrative clinical review

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: May 15, 2024

Treatment-resistant depression (TRD) occurs when at least two different antidepressants, taken the right dosage, for adequate period of time and with continuity, fail to give positive clinical effects. Esketamine, S-enantiomer ketamine, was recently approved TRD treatment from U.S. Food Drug Administration European Medicine Agency. Despite proved efficacy, many misconceptions by clinicians patients accompany this medication. We aimed review most common "false myths" regarding esketemine, counterarguing evidence-based facts.

Language: Английский

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Ketamine reduces the neural distinction between self- and other-produced affective touch: a randomized double-blind placebo-controlled study

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(11), P. 1767 - 1774

Published: June 25, 2024

A coherent sense of self is crucial for social functioning and mental health. The N-methyl-D-aspartate antagonist ketamine induces short-term dissociative experiences has therefore been used to model an altered state self-perception. This randomized double-blind placebo-controlled cross-over study investigated the mechanisms ketamine's effects on bodily in context affective touch. Thirty healthy participants (15 females/15 males, age 19-39) received intravenous or placebo while performing self-touch receiving touch by someone else during functional MRI - a previously established neural measure tactile self-other-differentiation. Afterwards, detection thresholds self- other-touch were assessed, as well states, interoceptive awareness, attitudes. Compared placebo, administration elicited dissociation reduced activity associated with self-other-differentiation right temporoparietal cortex, which was most pronounced other-touch. reduction correlated ketamine-induced reductions awareness. cortex showed higher connectivity somatosensory insula other- compared self-touch. difference augmented ketamine, strength cortex. These results demonstrate that disrupting self-experience through affects region involved perception cognition, especially regard else. process may be driven top-down signaling, rendering processing predictable self-generated unpredictable other-generated more similar. findings provide further evidence intricate relationship sense.

Language: Английский

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Experiences of Awe Mediate Ketamine’s Antidepressant Effects: Findings From a Randomized Controlled Trial in Treatment-Resistant Depression

Biological Psychiatry Global Open Science, Journal Year: 2024, Volume and Issue: 4(4), P. 100316 - 100316

Published: April 6, 2024

Ketamine, an NMDA-receptor antagonist, provides rapid anti-depressant effects. Although much research has focused on neural and molecular mechanisms of action, it is critical to also consider psychological that may contribute its therapeutic efficacy. The construct awe-inducing experience, which a well-validated phenomenon tied emotional well-being, not been previously applied in ketamine research. 116 participants with depression, n=77 who received infusion (0.5mg/kg over 40 minutes) n=39 patients saline placebo, completed validated measure awe (the AWE-scale) at minutes post-infusion. AWE-scores were examined as potential mediators depression outcomes (% improvement Montgomery-Asberg Depression Rating Scale (MADRS) %) five post-infusion timepoints (24 hours, 5, 12, 21, 30 days). Dissociative effects, measured by the Clinician-Administered Disassociation Symptoms (CADSS) scores, tested parallel mediation models for comparison. We found experience was strongly endorsed during (but infusion), there significant associations between total AWE-score MADRS change) arm all time points. Furthermore, time-points total-AWE score statistically mediated relationship MADRS. By contrast, CADSS scores did mediate any timepoint. Ketamine induced heightened feelings awe, these experiences consistently 1-to-30-day period, unlike general dissociative side specific awe-inspiring properties

Language: Английский

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Clinical pharmacological innovation in the treatment of depression

Expert Review of Clinical Pharmacology, Journal Year: 2023, Volume and Issue: 16(4), P. 349 - 362

Published: March 31, 2023

Deficiencies in standard of care antidepressants are driving novel drug discovery. A new age antidepressant medications has emerged with the introduction rapid-acting efficacy treatment-resistant patients.The newly approved medicines and those clinical development for major depressive disorder (MDD) documented this scoping review emerging antidepressants. Compounds evaluated efficacy, tolerability, safety compared to medicines.A discovery relies heavily on glutamatergic mechanisms. New based upon model ketamine have been delivered development. Rapid onset ability impact depression, raises question best first-line patients. Drugs improvements tolerability being investigated (e.g. mGlu2/3 receptor antagonists, AMPA potentiators, NMDA modulators). Multiple companies working toward identification psychedelic drugs where requirement activity is not fully known. Gaps still exist - methods matching patients specific needed, prevention MDD its disease progression need research attention.

Language: Английский

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At-home, telehealth-supported ketamine treatment for depression: Findings from longitudinal, machine learning and symptom network analysis of real-world data

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 361, P. 198 - 208

Published: May 27, 2024

Improving safe and effective access to ketamine therapy is of high priority given the growing burden mental illness. Telehealth-supported administration sublingual being explored toward this goal. In longitudinal study, moderately-to-severely depressed patients received four doses at home over weeks within a supportive digital health context. Treatment was structured resemble methods therapeutic psychedelic trials. Patients receiving second course treatment were also examined. Symptoms assessed using Patient Health Questionnaire (PHQ-9) for depression. We conducted preregistered machine learning symptom network analyses investigate outcomes (osf.io/v2rpx). A sample 11,441 analyzed, demonstrating modal antidepressant response from both non-severe (n = 6384, 55.8 %) severe 2070, 18.1 baseline depression levels. Adverse events detected in 3.0–4.8 % participants predominantly neurologic or psychiatric nature. helped extend improvements who responded favorably initial treatment. Improvement most strongly predicted by lower scores age baseline. Depressed mood Anhedonia sustained despite ongoing This study limited absence comparison control groups lack fixed-dose procedure administration. At-home, telehealth-supported largely safe, well-tolerated, associated with improvement Strategies combining psychedelic-oriented therapies rigorous telehealth models, as here, may uniquely address barriers

Language: Английский

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A transdiagnostic systematic review and meta-analysis of ketamine’s anxiolytic effects

Journal of Psychopharmacology, Journal Year: 2023, Volume and Issue: 37(8), P. 764 - 774

Published: April 2, 2023

Background: Ketamine may be effective in treating symptoms of anxiety, but the time profile ketamine’s anxiolytic effect is ill-defined. This systematic review and meta-analysis investigated ketamine at different points across a range clinical settings. Methods: Electronic databases were searched to capture randomised control trials measuring effects contexts including mood disorders, anxiety disorders chronic pain. Meta-analyses conducted using random-effects model. The correlations between (1) improvements mean depression scores, (2) peak dissociation scores also assessed. Results: In all, 14 studies met inclusion criteria. Risk bias was high 11 studies. significantly reduced compared placebo acute (<12 h; standard difference (SMD): −1.17, 95% confidence interval (CI) [−1.89, −0.44], p < 0.01), subacute (24 SMD: −0.44, CI [−0.65, −0.22], 0.01) sustained (7–14 days; −0.40, [−0.63, −0.17], points. Exploratory analyses revealed correlated both ( R 2 = 0.621, 0.035) 0.773, 0.021). relationship improvement not significant. Conclusions: appears offer rapid symptom relief settings, with occurring within first 12 h administration remaining for 1–2 weeks. Future could explore maintenance therapy on symptoms.

Language: Английский

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Differed spontaneous dissociative symptoms following the use of esketamine intranasal spray in a patient suffering from treatment-resistant depression: a case report

International Clinical Psychopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 22, 2024

Intranasal esketamine is used in France for treatment-resistant depression. Dissociative symptoms are common side effects during treatment sessions. We report a case of delayed spontaneous dissociative following administration. A 20-year-old female with depression received treatment. occurred sessions and persisted at distance, often accompanied by anxiety. Delayed phenomena disappeared within the fourth week esketamine. The literature mainly discusses dissociation sessions, limited data on differed episodes. Three hypotheses discussed concerning mechanism occurrence these phenomena, including esketamine’s direct effect, central nervous system sensitization, anxiety-induced dissociation. present first after intranasal administration Our main hypothesis suggests that may act as ‘pattern’ experiences, heightening patient’s ability to discern other instances dissociation, such acute anxiety attacks. Further research needed validate this hypothesis.

Language: Английский

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Acute Dissociation and Ketamine’s Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial

The International Journal of Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 27(4)

Published: April 1, 2024

Abstract Objective We sought to explore relationships of acute dissociative effects intravenous ketamine with change in depression and suicidal ideation plasma metabolite levels a randomized, midazolam-controlled trial. Methods Data from completed trial suicidal, depressed participants (n = 40) randomly assigned was used examine between treatment–emergent psychotomimetic symptoms pre/post-infusion changes severity. Nonparametric correlational statistics were used. These methods also associations or blood metabolites subset 28) who provided samples immediately post-infusion. Results Neither nor associated depressive pre- Norketamine had trend-level, moderate inverse correlation on Day 1 post-injection (P .064; P =.013 removing outlier). Dehydronorketamine correlated Clinician-Administered Dissociative States Scale scores at 40 minutes .034), 230 .014), .012). Conclusion did not find evidence that ketamine’s acute, transient dissociative, are its antidepressant anti-suicidal actions. The higher norketamine lower post-treatment suggests dissociation may be more an effect the parent drug.

Language: Английский

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