scholarly journals Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice

2021 ◽  
Vol 22 (17) ◽  
pp. 9225
Author(s):  
Rosa Estrada-Reyes ◽  
Daniel B. Quero-Chávez ◽  
Citlali Trueta ◽  
Armida Miranda ◽  
Marcela Valdés-Tovar ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Locomotor Activity ◽  
Depressive Disorder ◽  
Pineal Gland ◽  
Effective Dose ◽  
Antidepressant Effect ◽  
Low Doses ◽  
Major Depressive ◽  
Antidepressant Treatments ◽  
Collateral Effects

Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.

Is There a Delay in the Onset of the Antidepressant Effect of Electroconvulsive Therapy?

1994 ◽  
Vol 164 (1) ◽  
pp. 106-109 ◽  
Author(s):  
Colin R. Rodger ◽  
Allan I. F. Scott ◽  
Lawrence J. Whalley
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Antidepressant Effect ◽  
Major Depressive ◽  
Depressed Patients ◽  
Severity Of Depression ◽  
Drug Free ◽  
Hamilton Rating Scale

The severity of depression in 11 drug-free unipolar patients diagnosed with definite major depressive disorder was assessed using the Hamilton Rating Scale for Depression during a course (5–10 treatments) of bilateral electroconvulsive therapy (ECT). The degree of improvement after three treatments of ECT was six times greater than the improvement that occurred over the remainder of the course. Although depressed patients who recover with ECT require repeated treatments, the treatments early in a course of ECT can have marked antidepressant effect.

scholarly journals The Importance of Epigenetics in Diagnostics and Treatment of Major Depressive Disorder

2021 ◽  
Vol 11 (3) ◽  
pp. 167
Author(s):  
Piotr Czarny ◽  
Katarzyna Białek ◽  
Sylwia Ziółkowska ◽  
Justyna Strycharz ◽  
Gabriela Barszczewska ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Histone Deacetylases ◽  
Antidepressant Effect ◽  
Major Depressive ◽  
Non Coding Rna ◽  
Tight Association ◽  
Severity Of The Disease ◽  
Long Non Coding Rna

Recent studies imply that there is a tight association between epigenetics and a molecular mechanism of major depressive disorder (MDD). Epigenetic modifications, i.e., DNA methylation, post-translational histone modification and interference of microRNA (miRNA) or long non-coding RNA (lncRNA), are able to influence the severity of the disease and the outcome of the therapy. This article summarizes the most recent literature data on this topic, i.e., usage of histone deacetylases as therapeutic agents with an antidepressant effect and miRNAs or lncRNAs as markers of depression. Due to the noteworthy potential of the role of epigenetics in MDD diagnostics and therapy, we have gathered the most relevant data in this area.

scholarly journals Ketamine exerts a protective role in a cell-based model of major depressive disorder via the inhibition of apoptosis and inflammation and activation of the Krebs cycle

2019 ◽  
Author(s):  
Wenfei Zhang ◽  
Qian Sun ◽  
Lingling Jia ◽  
Ming Li
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Pc12 Cells ◽  
Inflammatory Cytokines ◽  
Krebs Cycle ◽  
Antidepressant Effect ◽  
Major Depressive ◽  
Apoptosis And Inflammation ◽  
Major Depressive Episodes ◽  
Pro Inflammatory Cytokines

Major depressive disorder (MDD) is one of the most common psychiatric disorders characterized by major depressive episodes. Although great efforts have been made to develop antidepressant drugs that target the monoaminergic system, these drugs are effective in only approximately 50% of MDD patients. In this study, we established a model of depression in PC12 cells using corticosterone to investigate the effect of ketamine and nuclear factor-κB (NF-κB) on the cell viability, apoptosis, levels of pro-inflammatory cytokines, apoptosis-related molecules, and enzymes of the Krebs cycle. PC12 cells were divided into control (no treatment, NC), ketamine treatment (KT), ketamine treatment with the inhibition of NF-κB (KI), and ketamine treatment with the overexpression of NF-κB (KO) group. Blood serum samples were collected from patients with MDD (n = 10) and healthy controls (n = 10) between 2015 and 2017. Ketamine significantly increased the viability and decreased the apoptosis of PC12 cells in KT and KI vs. NC group, but not in KO group. The levels of anti-apoptotic molecules and Krebs cycle enzymes were significantly increased in KI vs. KT group, while the levels of pro-apoptotic molecules and pro-inflammatory cytokines were decreased in KI vs. KT group. In addition, the levels of pro-inflammatory cytokines in the serum of MDD patients were significantly increased. The antidepressant effect of ketamine was enhanced in KI and reduced in KO group. Our results indicate that ketamine exerts its antidepressant effect via the inhibition of apoptosis and inflammation and the activation of the Krebs cycle in PC12 cells. NF-κB might be a potential therapeutic target in MDD.

scholarly journals Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives

2020 ◽  
Vol 17 (3) ◽  
pp. 181-192 ◽  
Author(s):  
Cheolmin Shin ◽  
Yong-Ku Kim
Keyword(s):  
Major Depressive Disorder ◽  
Nmda Receptor ◽  
Depressive Disorder ◽  
Clinical Symptoms ◽  
Antidepressant Effect ◽  
Rapid Improvement ◽  
Major Depressive ◽  
Onset Of Action ◽  
Level Of Evidence ◽  
Treatment Protocols

Major depressive disorder (MDD) is a serious psychiatric illness that causes functional impairment in many people. While monoaminergic antidepressants have been used to effectively treat MDD, these antidepressants have limitations in that they have delayed onset of action and many patients remain treatment-resistant. Therefore, there is a need to develop antidepressants with a novel target, and researchers have directed their attention to the glutamatergic system. Ketamine, although developed as an anesthetic, has been found to produce an antidepressant effect at sub-anesthetic doses via N-Methyl-D-aspartic acid (NMDA) receptor blockade as well as NMDA receptor- independent pathways. A single infusion of ketamine produced rapid improvement in clinical symptoms to a considerable level and led to the resolution of serious depressive symptoms, including imminent suicidal ideation, in patients with MDD. A series of recent randomized controlled trials have provided a high level of evidence for the therapeutic efficacy of ketamine treatment in MDD and presented new insights on the dose, usage, and route of administration of ketamine as an antidepressant. With this knowledge, it is expected that ketamine treatment protocols for MDD will be established as a treatment option available in clinical practice. However, long-term safety must be taken into consideration as ketamine has abuse potential and it is associated with psychological side effects such as dissociative or psychotomimetic effects.

Serotonin Transporter Gene: A New Polymorphism May Affect Response to Antidepressant Treatments in Major Depressive Disorder

2014 ◽  
Vol 18 (5) ◽  
pp. 567-577 ◽  
Author(s):  
Yoshihiko Matsumoto ◽  
Chiara Fabbri ◽  
Silvia Pellegrini ◽  
Stefano Porcelli ◽  
Pierluigi Politi ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Serotonin Transporter ◽  
Serotonin Transporter Gene ◽  
Transporter Gene ◽  
Major Depressive ◽  
Antidepressant Treatments
Sign in / Sign up

Export Citation Format

Share Document