Esketamine for Treatment-Resistant Depression — First FDA-Approved Antidepressant in a New Class

Kim, Jean; Farchione, Tiffany; Potter, Andrew; Chen, Qi; Temple, Robert

doi:10.1056/nejmp1903305

Cited by 250 publications

(163 citation statements)

References 5 publications

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…This finding is intriguing in light of the fact that ketamine itself is a potent antidepressant and an intranasal formulation was recently approved in the United States for treatment of MDD. 10 Psychomimetic, cardiovascular, and neurological side effects are frequently reported in studies examining the use of ketamine for the treatment of depression. 11 That said, it is difficult to compare the psychiatric patient population with the perioperative patient population.…”

Section: Discussionmentioning

confidence: 99%

<p>Evaluation of Clinical Factors Associated with Adverse Drug Events in Patients Receiving Sub-Anesthetic Ketamine Infusions</p>

Stoker¹,

Rosenfeld²,

Buras³

et al. 2019

JPR

View full text Add to dashboard Cite

Introduction: Sub-anesthetic ketamine is frequently used as an analgesic to reduce perioperative opioid consumption and has also been shown to have antidepressant effects. Side effects of ketamine include dizziness, diplopia, nystagmus, and psychomimetic effects. It is unclear what clinical factors may be associated with ketamine-related adverse drug events (ADEs). Methods: We performed a retrospective review of 95 patients who received sub-anesthetic ketamine infusions at our institution. Data examined associations between ketamine-related ADEs and various clinical characteristics including chronic pain, depression, or psychiatric disorder, patient physical characteristics, chronic opioid use, perioperative opioid use, dose and duration of ketamine infusions, pain scores, and perioperative medications such as serotonergic agents, central nervous system (CNS) depressants, and analgesics. Results: Overall incidence of ketamine-related ADEs was 29.5% and the incidence of psychomimetic effects was 14.8%. We observed that patients with a history of depression have a lower incidence of ketamine-related ADEs compared to patients without a history of depression (10.3% vs 37.3%; p value = 0.007). Conclusion: Patients with depression were found to have a statistically significant reduction in the incidence of ketamine-related ADEs. We found no statistically significant positive associations between ketamine-related ADEs and other clinical factors such as a history of chronic pain, psychiatric disease, patient physical characteristics, perioperative opioid use, dose of ketamine infusion, or co-administration of other CNS depressants.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Evaluation of Clinical Factors Associated with Adverse Drug Events in Patients Receiving Sub-Anesthetic Ketamine Infusions</p>

Stoker¹,

Rosenfeld²,

Buras³

et al. 2019

JPR

View full text Add to dashboard Cite

show abstract

“…Ketamine is widely used in clinical analgesia and sedation for decades . At present, nasal spray esketamine is also indicated for treatment‐resistant depression . Clinical applications of ketamine cause iatrogenic dissociation and emergent delirium; these effects lead to the recreational abuse of ketamine in nightclubs and dance parties.…”

Section: Introductionmentioning

confidence: 99%

“…2 At present, nasal spray esketamine is also indicated for treatment-resistant depression. 3 Clinical applications of ketamine cause iatrogenic dissociation and emergent delirium; these effects lead to the recreational abuse of ketamine in nightclubs and dance parties. The recreational use of ketamine has become endemic worldwide, particularly in the United Kingdom, Australia, Italy, China, Southeast Asia, and East Europe.…”

Section: Introductionmentioning

confidence: 99%

Ba‐Wei‐Die‐Huang‐Wan (Hachimi‐jio‐gan) can ameliorate ketamine‐induced cystitis by modulating neuroreceptors, inflammatory mediators, and fibrogenesis in a rat model

Lee

Tain

Chuang

et al. 2019

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aim We investigated the effects of Ba‐Wei‐Die‐Huang‐Wan (BWDHW) on ketamine‐induced cystitis (KIC) in a rat model. Methods Female Sprague‐Dawley rats were distributed into three groups: control (saline), ketamine (25 mg/kg/day for 28 days), or ketamine (25 mg/kg/day for 28 days) plus BWDHW (90 mg/kg/day, started from day 14). Functional magnetic resonance imaging (fMRI), metabolic cage study, and cystometry were evaluated. Bladder histology was evaluated. Western blots of the bladder proteins were carried out. Results Compared with controls, ketamine‐treated rats showed stronger fMRI intensity in the periaqueductal gray area and bladder overactivity in the bladder functional study, but the ketamine/BWDHW‐treated rats did not. Furthermore, ketamine breached the uroplakin III membrane at the apical surface of the urothelium, enhanced substance P spread over the urothelium, induced suburothelial hemorrhage and monocyte/macrophage infiltration, and caused interstitial fibrosis deposition. By contrast, the BWDHW‐treated rats exhibited less substance P spread, lower suburothelial monocyte/macrophage infiltration, and lower interstitial fibrosis deposition. The ketamine group showed significant overexpression of neuroreceptors in the bladder mucosa (the transient receptor potential vanilloid 1 and M2‐ and M3‐muscarinic receptors) and detrusor (M2‐ and M3‐muscarinic receptors); inflammatory mediators in the detrusor (interleukin‐1β [IL‐1β], IL‐6, tumor necrosis factor‐α, nuclear factor‐κB, cyclooxygenase‐2, and intercellular adhesion molecule‐1); and fibrogenesis molecules in the detrusor (transforming growth factor‐β1, collagen I, collagen III, and fibronectin). However, no significant changes were noted between the ketamine/BWDHW and control groups. Conclusion BWDHW could exert therapeutic effects by inhibiting the upregulation of neuroreceptors, modulating inflammatory mediators, suppressing fibrogenesis, and ameliorating bladder overactivity in rats with KIC.

show abstract

“…Most of the reduction in the esketamine arm was also seen with placebo. The four point difference between drug and placebo reached a significance of P<0.05 in some trials only if a one sided P value was used 9. Despite these small changes and no evidence of a persistent, clinically relevant, benefit, the FDA approval was accompanied by press coverage7 and the drug heralded as a “first in class” treatment in the New England Journal of Medicine 9…”

Section: Promotion Of Small Effectsmentioning

confidence: 99%

The trouble with antidepressants: why the evidence overplays benefits and underplays risks—an essay by John B Warren

Warren

2020

BMJ

View full text Add to dashboard Cite

show abstract

Esketamine for Treatment-Resistant Depression — First FDA-Approved Antidepressant in a New Class

Cited by 250 publications

References 5 publications

<p>Evaluation of Clinical Factors Associated with Adverse Drug Events in Patients Receiving Sub-Anesthetic Ketamine Infusions</p>

<p>Evaluation of Clinical Factors Associated with Adverse Drug Events in Patients Receiving Sub-Anesthetic Ketamine Infusions</p>

Ba‐Wei‐Die‐Huang‐Wan (Hachimi‐jio‐gan) can ameliorate ketamine‐induced cystitis by modulating neuroreceptors, inflammatory mediators, and fibrogenesis in a rat model

The trouble with antidepressants: why the evidence overplays benefits and underplays risks—an essay by John B Warren

Contact Info

Product

Resources

About