Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

Niciu, Mark J.; Henter, Ioline D.; Luckenbaugh, David A.; Zarate, Carlos A.; Charney, Dennis S.

doi:10.1146/annurev-pharmtox-011613-135950

Cited by 152 publications

(124 citation statements)

References 133 publications

(156 reference statements)

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“…We have recently reviewed the growing clinical literature on ketamine's antidepressant efficacy and treatment response biomarkers [Niciu et al 2014a[Niciu et al , 2014c. In this section, we will provide an update on additional studies published since those reports.…”

Section: Clinical Studiesmentioning

confidence: 99%

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

Iadarola

Niciu

Richards

et al. 2015

Therapeutic Advances in Chronic Disease

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182

117

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Current pharmacotherapies for major depressive disorder (MDD) and bipolar depression (BDep) have a distinct lag of onset that can generate great distress and impairment in patients. Furthermore, as demonstrated by several real-world effectiveness trials, their efficacy is limited. All approved antidepressant medications for MDD primarily act through monoaminergic mechanisms, agonists or antagonists with varying affinities for serotonin, norepinephrine and dopamine. The glutamate system has received much attention in recent years as an avenue for developing novel therapeutics. A single subanesthetic dose infusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been shown to have rapid and potent antidepressant effects in treatment-resistant MDD and BDep. In a reverse translational framework, ketamine's clinical efficacy has inspired many preclinical studies to explore glutamatergic mechanisms of antidepressant action. These studies have revealed enhanced synaptic plasticity/synaptogenesis via numerous molecular and cellular mechanisms: release of local translational inhibition of brain-derived neurotrophic factor and secretion from dendritic spines, mammalian target of rapamycin activation and glycogen synthase kinase-3 inhibition. Current efforts are focused on extending ketamine's antidepressant efficacy, uncovering the neurobiological mechanisms responsible for ketamine's antidepressant activity in biologically enriched subgroups, and identifying treatment response biomarkers to personalize antidepressant selection. Other NMDA receptor antagonists have been studied both preclinically and clinically, which have revealed relatively modest antidepressant effects compared with ketamine but potentially other favorable characteristics, for example, decreased dissociative or psychotomimetic effects; therefore, there is great interest in developing novel glutamatergic antidepressants with greater target specificity and/or decreased adverse effects.

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Section: Clinical Studiesmentioning

confidence: 99%

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

Iadarola

Niciu

Richards

et al. 2015

Therapeutic Advances in Chronic Disease

Self Cite

182

117

View full text Add to dashboard Cite

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“…Numerous data sustain the view that the rapid antidepressant effect of ketamine relies on fast changes in dendritic organization (Niciu et al, 2014). In contrast, psychotomimetic effects of NMDAR blockade may result from overactivation of certain cortical areas.…”

Section: Discussionmentioning

confidence: 95%

“…Glutamatergic drugs like the NMDAR antagonist ketamine may represent valuable alternative drugs, showing fast onset within few hours and sustained therapeutic action lasting up to 2 weeks (Berman et al, 2000). Three main targets for the anti-depressive action of ketamine have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3) (Niciu et al, 2014). However, it remains unclear, if only these molecular pathways are responsible for the rapid, longlasting antidepressant effect of ketamine.…”

Section: Introductionmentioning

confidence: 99%

Role of the nitric oxide donor sodium nitroprusside in the antidepressant effect of ketamine in mice

Vogt

Vogel

Pfeiffer

et al. 2015

European Neuropsychopharmacology

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“…In their recent review, Niciu et al (28) highlight several other glutamate antagonists that have had some degree of clinical investigation. The NMDA receptor antagonist memantine showed initial promise as a potential antidepressant based on preclinical data and supported by its clinical utility in dementia, but initial clinical trials to examine antidepressant efficacy did not yield significant effects (28).…”

Section: Other Glutamate Receptor Antagonistsmentioning

confidence: 99%

“…The NMDA receptor antagonist memantine showed initial promise as a potential antidepressant based on preclinical data and supported by its clinical utility in dementia, but initial clinical trials to examine antidepressant efficacy did not yield significant effects (28). NR2B-selective NMDA antagonists have been investigated, such as CP-101,166 and MK 0657.…”

Section: Other Glutamate Receptor Antagonistsmentioning

confidence: 99%

Optimization of Treatment Algorithms for Clinical Depression: Glutamate Antagonists and Transcranial Magnetic Stimulation as Case Examples

Greer¹,

Trivedi²

2014

FOC

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Clinical Context: Current treatment approaches for depression are still largely based on trial and error, necessitating adequate guidance for sequential treatment selection and maintenance. Issues surrounding the adequate implementation and integration of evidence-based treatment approaches, particularly as they relate to novel approaches and combination strategies, remain an important concern. Treatment Strategies and Evidence: Treatment guidelines and algorithms have been associated with improved outcomes. Utilization of measurement-based care (MBC) provides a simple and effective way to optimize personalized evidence-based medical care based on current treatment guidelines. Because current treatments lead to only modest outcomes, incorporating the use of novel treatments is desirable. However, ways in which promising treatments can effectively and appropriately be incorporated into treatment algorithms requires careful assessment of risks and benefits. Questions and Controversy: Utilization of treatment guidelines and algorithms in practice has been fairly slow to occur, although MBC approaches have aided in better adoption of evidence-based clinical practice guidelines into standard care. A balance must be struck between adopting insufficiently studied novel treatments and rapid dissemination of evidence-based treatments via treatment guidelines and algorithms. Recommendations: MBC is critical to personalization of evidence-based treatment selection and optimization of treatment outcomes. Incorporation of biomarker data into treatment selection and maintenance will be critical to improve personalization of treatment in the future.

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Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

Cited by 152 publications

References 133 publications

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

Role of the nitric oxide donor sodium nitroprusside in the antidepressant effect of ketamine in mice

Optimization of Treatment Algorithms for Clinical Depression: Glutamate Antagonists and Transcranial Magnetic Stimulation as Case Examples

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