Abstract Background Low-dose racemic ketamine enhances the firing rate and burst activity of rat norepinephrine neurons in the locus coeruleus, as well as the population activity of dopamine neurons in the ventral tegmental area [El Iskandrani et al, 2015]. These brainstem monoamine nuclei densely innervate the prefrontal cortex (PFC), whereas clinical studies have shown a facilitation of...
Abstract Metabolic, inflammatory, and neurotrophic measures may provide complementary insight into biological heterogeneity underlying treatment-resistant depression and response to ketamine-based treatments. However, biomarker studies of ketamine treatment have focused on individual markers or biological domains, most commonly inflammatory or neurotrophic, while metabolic measures remain...
Abstract Background In preclinical studies, an increase in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-D-aspartate (NMDA) receptor throughput is the predominant hypothesis posited to explain the rapid antidepressant effect of ketamine and S-ketamine. Several lines of evidence show that this AMPA increase takes place in the medial prefrontal cortex (mPFC), which...
Abstract Background Low dose ketamine has been shown, in animal studies, to enhance firing activity of norepinephrine neurons in the locus coeruleus, and burst as well as population activity of dopamine neurons in the ventral tegmental area [1]. These brainstem monoamine nuclei densely innervate the PFC, where clinical studies have shown a facilitation of glutamatergic neurotransmission in the...
A sub-anesthetic dose of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, produces robust antidepressant effects in treatment-resistant major depressive disorder (MDD). The mismatch negativity (MMN) is reliant on glutamatergic neurotransmission and reduced by NMDAR antagonists. The MMN may characterise the neural mechanisms underlying ketamine's effects. This study examined the...
Abstract Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar...
Abstract Background Subanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment. Methods Thirty-eight patients with treatment-resistant depression were administered cognitive...
OBJECTIVE: -methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice. METHODS: A systematic review was conducted with...
Background Recent evidence underscores the utility of rapid-acting antidepressant interventions, such as ketamine, in alleviating symptoms of major depressive episodes (MDE). However, to date, there have been limited head-to-head comparisons of intravenous (IV) ketamine infusions with other antidepressant treatment strategies in large randomized trials. This study protocol describes an ongoing...
BACKGROUND: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression. METHODS: This Phase 3, double-blind, multicenter study enrolled adults with moderate-to-severe depression and nonresponse to ≥2 antidepressants in the current depression episode. Eligible patients (N = 346)...
Importance: Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. Objective: To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable...
OBJECTIVE Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance...
Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the...
Abstract The sustained administration of the 5‐HT 1A agonist gepirone (15 mg/kg/day, s.c.) in the rat produced an initial decrease of the firing activity of dorsal raphe 5‐HT neurons which was followed by a progressive recovery to normal after 14 days of treatment. At this point in time, the effect of intravenous lysergic acid diethylamide (LSD) on the firing activity of 5‐HT neurons was...