Intravenous Ketamine for Treatment-Resistant Major Depressive Disorder

Covvey, Jordan R.; Crawford, Alexis N.; Lowe, Denise

doi:10.1345/aph.1q371

Cited by 46 publications

(29 citation statements)

References 33 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…8 Ketamine treatment produces antidepressant efficacy within hours of administration in 70% of treatment-resistant MDD patients. Symptom improvement usually lasts for a week or longer 9 but in general its therapeutic effects are short-lived. 10 Other glutamatergic agents, such as amantadine 11 and riluzole [12][13][14] are also potentially therapeutic in depression.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in glutamate receptor gene expression in major depression and suicide

et al. 2015

View full text Add to dashboard Cite

Accumulating data indicate that the glutamate system is disrupted in major depressive disorder (MDD), and recent clinical research suggests that ketamine, an antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor (GluR), has rapid antidepressant efficacy. Here we report findings from gene expression studies of a large cohort of postmortem subjects, including subjects with MDD and controls. Our data reveal higher expression levels of the majority of glutamatergic genes tested in the dorsolateral prefrontal cortex (DLPFC) in MDD (F21,59=2.32, P=0.006). Posthoc data indicate that these gene expression differences occurred mostly in the female subjects. Higher expression levels of GRIN1, GRIN2A-D, GRIA2-4, GRIK1-2, GRM1, GRM4, GRM5 and GRM7 were detected in the female patients with MDD. In contrast, GRM5 expression was lower in male MDD patients relative to male controls. When MDD suicides were compared with MDD non-suicides, GRIN2B, GRIK3 and GRM2 were expressed at higher levels in the suicides. Higher expression levels were detected for several additional genes, but these were not statistically significant after correction for multiple comparisons. In summary, our analyses indicate a generalized disruption of the regulation of the GluRs in the DLPFC of females with MDD, with more specific GluR alterations in the suicides and in the male groups. These data reveal further evidence that, in addition to the NMDA receptor, the AMPA, kainate and the metabotropic GluRs may be targets for the development of rapidly acting antidepressant drugs.

show abstract

Section: Introductionmentioning

confidence: 99%

Sex differences in glutamate receptor gene expression in major depression and suicide

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Based on the antidepressantlike activity of NMDA/glutamate receptor antagonists a link between hyperactivity of the glutamate system and depression was indicated [19,48,49,53,65]. Additionally, glutamate receptor antagonists or its modulators showed antidepressant properties in treatment refractory depression [1,9,13,14,27,28,41,44,71,72]. Hyperactivity of the glutamatergic system was also observed in animals after both a 2-[63] and 4-week [58,61] zinc deficient diet.…”

Section: Zinc Deficiency Alters Responsiveness To Antidepressantsmentioning

confidence: 99%

Zinc deficiency alters responsiveness to antidepressant drugs in mice

Młyniec

Budziszewska

Reczyński

et al. 2013

Pharmacological Reports

View full text Add to dashboard Cite

Abstract:Background: There is some evidence coming from preclinical and clinical studies suggesting a relationship between dietary zinc intake and depressive symptoms. The aim of the study was to determine whether zinc deficiency alters the response to antidepressants with a different mechanism of action. We examine also whether these changes are related to activity of the hypothalamic-pituitaryadrenal HPA axis. Methods: Male CD-1 mice were assigned to groups according to diet and antidepressant administration. To evaluate animal behavior, the immobility time in the forced swim test (FST) and locomotor activity were measured. To determine serum zinc levels the flame atomic absorption spectroscopy (FAAS) was used. The serum corticosterone was determined by radioimmunoassay (RIA). Results: Antidepressants administered to zinc-deprived mice induced an altered response in the FST when compared to animals fed with an adequate diet. There were no changes in locomotor activity. Animals subjected to a zinc-deficient diet showed a significant reduction in serum zinc levels, which was normalized by antidepressant treatment. An increase in serum corticosterone concentrations in mice fed with a zinc-deficient diet and treated with antidepressants was observed, so it can be concluded that reduced levels of zinc contribute hyperactivation of the HPA axis. Conclusion:The results of this study suggest that a diet with a reduced zinc level alters antidepressant action, which is associated with a reduction in the serum zinc level and rise in the corticosterone level. The results of this study may indicate the involvement of zinc deficiency in the pathogenesis of depression.

show abstract

“…5 Unlike other antidepressants, ketamine improves symptoms, including suicidal thoughts, within hours or minutes. 7,8 To date there have been numerous open label trials of ketamine and it appears to be a promising treatment but large scale placebo controlled clinical trials are needed to determine if it can be used successfully to treat depression in standard clinical practice. [5][6][7][8][9][10]14 Depression often returns within a few days of the first ketamine treatment and the larger clinical trials will help determine how many consecutive doses are required to sustain remission.…”

Section: Ketaminementioning

confidence: 99%

“…However, a new treatment, ketamine, a dissociative anesthetic, can alter depressive symptoms within hours or even minutes. [5][6][7][8][9][10] Ketamine can stop suicidal thoughts in as little as 20 minutes and is being developed to treat suicidal patients in the emergency room and allow them to return home and avoid hospitalization. 7 Rapid changes in a belief as complex as suicide raise new questions about the self and identity.…”

Section: Introductionmentioning

confidence: 99%

Depression, Ketamine Treatment, and the Theater of Consciousness

Cerullo¹,

Stryker²

2016

ujp

View full text Add to dashboard Cite

In severe depression thoughts of suicide can develop over weeks or months. Traditional pharmacologic or psychotherapeutic treatments take several weeks before they begin to improve symptoms. This gradual improvement is consistent with our everyday experience of the self. However, a new treatment, ketamine, can alter depressive symptoms within hours or even minutes. Ketamine can stop suicidal thoughts in as little as 20 minutes and is being developed to treat suicidal patients in the emergency room. Rapid changes in a belief as complex as suicide raise new questions about the self and identity. More complicated models of the self are required to understand how rapid changes in complex beliefs are possible without invoking unrealistic specificity in the brain (i.e. grandmother cells for belief). If the brain has multiple competing selves within modules then ketamine could work by either turning a self module on or off. This is consistent with a modified version of the global workspace theory of consciousness where a self module provides the context for the spotlight of attention.

show abstract

Intravenous Ketamine for Treatment-Resistant Major Depressive Disorder

Abstract: Ketamine for treatment-resistant MDD requires further evaluation before it can be considered a viable treatment option.

Cited by 46 publications

References 33 publications

Sex differences in glutamate receptor gene expression in major depression and suicide

Sex differences in glutamate receptor gene expression in major depression and suicide

Zinc deficiency alters responsiveness to antidepressant drugs in mice

Depression, Ketamine Treatment, and the Theater of Consciousness

Contact Info

Product

Resources

About