International Immunopharmacology
August 1, 2019
Daiyue Chang, Jinghua Zhao, Xintong Zhang et al.
Depression has become a common mental illness, and studies have shown that neuroinflammation is associated with depression. Ketamine is a rapid antidepressant. In order to obtain better antidepressant effects, it is necessary to explore the efficacy of combination therapy with ketamine and other antidepressants. DHA is an unsaturated fatty acid with excellent application prospects due to its...
Behavioural Brain Research
August 1, 2019
Zhongwei Xiong, Yuko Fujita, Kai Zhang et al.
Inflammatory bone markers may play a role in the antidepressant actions of (R)-ketamine in susceptible mice after chronic social defeat stress (CSDS). In this study, we compared the effects of (R)-ketamine and its final metabolite (2R,6R)-hydroxynorketamine (HNK) in depression-like phenotypes, inflammatory bone markers and bone mineral density (BMD) in CSDS susceptible mice. We measured plasma...
Heliyon
August 1, 2019
Steve Best, Dan G. Pavel, Natalie Haustrup
34 citations
Background Both transcranial magnetic stimulation (TMS) and infused ketamine are recognized treatments for patients suffering from major depressive disorder (MDD). A novel therapy named combination TMS with ketamine (CTK) is introduced. This retrospective review examined the safety and clinical benefits of CTK in patients suffering from treatment-resistant depression (TRD) during the routine...
Drug Design, Development and Therapy
August 1, 2019
Alexandrine Corriger, G. Pickering
197 citations
Abstract Depression is the third leading cause of disability in the world. Depressive symptoms may be reduced within several weeks after the start of conventional antidepressants, but treatment resistance concerns one-third of patients who fail to achieve recovery. Over the last 20 years, ketamine, an antagonist of the N-methyl-D-aspartate receptor, has been described to have antidepressant...
The British Journal of Psychiatry
August 1, 2019
Álvaro López-díaz, Manuel Murillo-Izquierdo, Elisa Moreno-Mellado
21 citations
Ketamine therapy for treatment-resistant depression in European national health systems may only be considered after attempting all evidence-based antidepressant strategies outlined in clinical guidelines. This paper seeks to explain the ethical, regulatory and procedural framework for the off-label use of ketamine for treatment-resistant depression within a public healthcare system.Declaration...
BJPsych Open
July 29, 2019
Sagar Jilka, Claire A. Murray, Ania M. Wieczorek et al.
20 citations
BACKGROUND: Only one-third of patients with major depressive disorder achieve remission. One new and promising treatment, ketamine, may prove challenging to implement because of its abuse potential. Although clinicians' views have been sought, we need patients' views before large scale roll-out is considered. AIMS: To explore patients' and carers' views to inform policy and practical decisions...
Pharmacology, Biochemistry, and Behavior
July 23, 2019
Qing Li, Huiran Wu, Shu-Juan Fan et al.
Ketamine has become increasingly popular in adolescent drug abusers worldwide. Meanwhile, alcohol is usually used by ketamine users. However, little work has been conducted to examine the chronic combined effects of ketamine and ethanol on adolescent brain. Here we probed into the effects of chronic administration of ketamine at recreational doses alone or combined with ethanol on behaviors and...
The International Journal of Neuropsychopharmacology
July 16, 2019
Yukio Ago, Wataru Tanabe, Momoko Higuchi et al.
91 citations
BACKGROUND: Although recent studies provide insight into the molecular mechanisms of the effects of ketamine, the antidepressant mechanism of ketamine enantiomers and their metabolites is not fully understood. In view of the involvement of mechanisms other than the N-methyl-D-aspartate receptor in ketamine's action, we investigated the effects of (R)-ketamine, (S)-ketamine, (R)-norketamine...
The International Journal of Neuropsychopharmacology
July 9, 2019
Maggie Fedgchin, Madhukar H. Trivedi, Ella Daly et al.
593 citations
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)...
Journal of Molecular Neuroscience
July 2019
Cheng Jiang, Wei-Jye Lin, Stephen R Salton
Members of the neurotrophin family and in particular brain-derived neurotrophic factor (BDNF) regulate the response to rapid- and slow-acting chemical antidepressants and voluntary exercise. Recent work suggests that rapid-acting antidepressants that modulate N-methyl-D-aspartate receptor (NMDA-R) signaling (e.g., ketamine and GLYX-13) require expression of VGF (non-acronymic), the...
The Brown University Psychopharmacology Update
July 1, 2019
A study examining the effects of single, repeated, and maintenance doses of ketamine on patients with treatment‐resistant depression has found cumulative and sustained antidepressant effects from six infusions administered three times a week over 2 weeks. The study also found that among responders to the repeated infusions, antidepressant response was generally maintained with weekly infusions...
British Journal of Pharmacology
July 1, 2019
Panos Zanos, Jaclyn N. Highland, Xin Liu et al.
(R)-Ketamine (arketamine) may have utility as a rapidly acting antidepressant. While (R)-ketamine has lower potency than (R,S)-ketamine to inhibit NMDA receptors in vitro, the extent to which (R)-ketamine shares the NMDA receptor-mediated adverse effects of (R,S)-ketamine in vivo has not been fully characterised. Furthermore, (R)-ketamine is metabolised to (2R,6R)-hydroxynorketamine (HNK),...
Pharmacology & Therapeutics
July 1, 2019
T. H. Pham, Alain M. Gardier
190 citations
Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor, displays a fast antidepressant activity in treatment-resistant depression and in rodent models of anxiety/depression. A large body of evidence concerning the cellular and molecular mechanisms underlying its fast antidepressant-like activity comes from animal studies. Although structural remodeling of...
American Journal of Psychiatry
June 24, 2019
Elias Dakwar, E. Nunes, C. Hart et al.
179 citations
OBJECTIVE Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. METHODS Fifty-five cocaine-dependent...
Psychiatry and Clinical Neurosciences
June 19, 2019
Kenji Hashimoto
325 citations
Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one‐third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists...
CNS Spectrums
June 19, 2019
Gregor Hasler
31 citations
In major depression, remission rate in response to monoaminergic antidepressant is around 50%. The lack of strong synergies between classical antidepressants and psychotherapy may be due to the molecular effects of classical antidepressants. They modulate synapses but they do not substantially influence synaptogenesis. They also increase brain-derived neurotrophic factor (BDNF). However, for...
Frontiers in Neuroscience
June 18, 2019
Birgit Derntl, J. Hornung, Z. Sen et al.
Ketamine is a drug that reduces depressive and elicits schizophrenia-like symptoms in humans. However, it is largely unexplored whether women and men differ with respect to ketamine-action and whether age contributes to drug-effects. In this study we assessed dissociative symptoms via the Clinician Administered Dissociative States Scale (CADSS) in a total of 69 healthy subjects aged between 18...
JAMA Psychiatry
June 5, 2019
Ella Daly, Madhukar H. Trivedi, Adam Janik et al.
766 citations
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...
Nature Communications
June 3, 2019
Farhan Ali, Danielle M. Gerhard, Katherine Sweasy et al.
201 citations
A subanesthetic dose of ketamine causes acute psychotomimetic symptoms and sustained antidepressant effects. In prefrontal cortex, the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as ketamine act preferentially on GABAergic neurons. However, cortical interneurons are heterogeneous. In particular, somatostatin-expressing (SST)...
Molecular Neurobiology
June 1, 2019
Samuel Kohtala, Wiebke Theilmann, Marko Rosenholm et al.
Rapid antidepressant effects of ketamine become most evident when its psychotomimetic effects subside, but the neurobiological basis of this "lag" remains unclear. Laughing gas (N2O), another NMDA-R (N-methyl-D-aspartate receptor) blocker, has been reported to bring antidepressant effects rapidly upon drug discontinuation. We took advantage of the exceptional pharmacokinetic properties of N2O...