Major depressive disorder (MDD) is a highly prevalent and debilitating illness and closely linked to suicide risk. Currently available antidepressants take weeks to work and have low remission rates; indeed, about a third of individuals with MDD fail to fully remit in response to these agents. Novel therapies that target the glutamatergic system—such as ketamine—offer rapid antidepressant...
Background: Conventional antidepressants are thought to produce their impact on clinical symptoms by increasing the central availability of biogenic amine neurotransmitters (the monoamine hypothesis of depression). These drugs continue to be the primary medicines used in major depressive disorder. Although they have biological effects after acute dosing, full antidepressant response generally...
After much time and investment, several new classes of antidepressants may soon be available. When ketamine was found to exert a rapid antidepressant effect by researchers at the National Institute of Mental Health (NIMH) more than a decade ago, it sparked hope for a new generation of treatments for depressive disorders. Now, new drug candidates are finally edging toward the finish line....
K anesthesia was introduced about half a century ago. In recent decades, this drug, in subanesthetic doses, has also demonstrated efficacy for off-label indications including treating acute and chronic pain, treating agitation, treating depression, and inducing sedation. Thus, there are studies of subanesthetic dosing with ketamine for treating pain in emergency medicine settings, treating...
BACKGROUND: Off-label ketamine treatment has shown acute antidepressant effects that offer hope for patients with therapy-resistant depression. However, its potential for integration into treatment algorithms is controversial, not least because the evidence base for maintenance treatment with repeated ketamine administration is currently weak. Ketamine is also a drug of misuse, which has raised...
BrainAugust 1, 2018Tineke Grent-'t-Jong, Davide Rivolta, Joachim Gross et al.
Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded...
Though several promising investigational compounds that regulate glutamate signaling have faltered in recent clinical studies, upcoming data on esketamine and rapastinel may turn the tide. When the anesthetic ketamine was first shown to have strong and rapid antidepressant properties back in 2000, it triggered a wave of excitement in the psychiatric community. Studies of mood disorders have...
Rev Bras Psiquiatr. 2018;40:110 Brazilian Journal of Psychiatry 00000000-0002-7316-1185 | doi:10.1590/1516-4446-2017-2380 Singh et al. reported that two or three weekly 40 min i.v. infusions of ketamine (0.5 mg/kg) are safe and effective for maintaining an acute response to ketamine during one month of treatment for resistant depression (TRD). We present herein the results of an open label...
LEARNING OBJECTIVE: After participating in this activity, learners should be better able to evaluate the evidence supporting the antidepressant effects of glutamatergic modulators.Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions...
Background: Subanesthetic dosages of the NMDAR antagonist, S-Ketamine, can cause changes in behavior in healthy subjects, which are similar to the state acute psychosis and are relevant in translational schizophrenia research. Functional magnetic resonance imaging (fMRI) can be used for non-hypothesis-driven analysis of brain connectivity. The correlation between clinical behavioral scores and...