Ketamine rapidly reduces suicidal ideation in major depressive disorder (MDD), but its effects are transient. Preclinical and clinical studies suggest that ketamine's antidepressant and antisuicidal effects may be partly mediated by mu-opioid receptor (MOR) modulation. The authors investigated the efficacy and safety of low-dose sublingual buprenorphine, a partial MOR agonist, as a follow-on...
Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform...
Ketamine and esketamine have been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior in adults. The current paper aimed to systematically review the available data on their efficacy in children and adolescents. The MEDLINE was searched with the keyword 'esketamine' on July 5th, 2024 (by following the PRISMA statement)....
Igor D Bandeira, MD, PhD, Luke A Jelen, MD, PhD, Jason M Tucciarone, MD, PhD, Boris D Heifets, MD, PhD, Carolyn I Rodriguez, MD, PhD, Alan F Schatzberg, MD
Since the last edition of the Black Book, several innovative agents have been approved or are poised to be approved in the coming year. These include novel antidepressants, the first muscarine agonist for the treatment of schizophrenia, the first psychedelic which may be approved for the treatment of PTSD (Post Traumatic Stress Disorder), and the first disease modifying drug for the treatment...
Structured Abstract Importance Ketamine has well known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Given prior studies that link specific cortical oscillations with specific therapeutic effects, it is likely that modulating selective aspects...
The endogenous opioid system is thought to play a role in the placebo antidepressant response. A recent trial comparing the rapid antidepressant effects of ketamine versus placebo in surgical patients, some of whom were on chronic opioid therapy, revealed a substantial placebo effect. This finding provided an opportunity to test the hypothesis that opioid agonist exposure interacts with placebo...
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 and meta-analysis of the available data on its efficacy against depression and suicidality as well as its side effects. MEDLINE was searched with the keyword "esketamine" on March 24, 2024, using...
Ketamine is a racemic compound and medication comprised of (S)-ketamine and (R)-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders...
The endogenous opioid system is thought to play a role in the placebo antidepressant response. A recent trial comparing the rapid antidepressant effects of ketamine versus placebo in surgical patients, some of whom were on chronic opioid therapy, revealed a substantial placebo effect. This finding provided an opportunity to test the hypothesis that opioid agonist exposure interacts with placebo...
Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. Here we present a single-center, parallel-arm, triple-masked, randomized, placebo-controlled trial assessing the antidepressant efficacy of intravenous ketamine masked by surgical anesthesia (ClinicalTrials.gov, NCT03861988). Adult patients (N = 40) with...
Abstract BACKGROUND Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. METHODS In a triple-masked, randomized, placebo-controlled trial, 40 adult patients with major depressive disorder were randomized to a single infusion of ketamine (0.5 mg/kg) or placebo (saline) during anesthesia as usual for routine...
Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties...
OBJECTIVE: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects. METHOD: In a proposed double-blind crossover study of 30 adults with treatment-resistant...
IMPORTANCE: Several studies now provide evidence of ketamine hydrochloride's ability to produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment. Despite the relatively small sample sizes, lack of longer-term data on efficacy, and limited data on safety provided by these studies, they have led to increased use of...