Ketamine and other glutamate receptor modulators for depression in adults with bipolar disorder.
Ontology highlight
ABSTRACT:
SUBMITTER: Dean RL
PROVIDER: S-EPMC8499740 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Ketamine and other glutamate receptor modulators for depression in adults with bipolar disorder.
Dean Rebecca L RL Marquardt Tahnee T Hurducas Claudia C Spyridi Styliani S Barnes Annabelle A Smith Rebecca R Cowen Philip J PJ McShane Rupert R Hawton Keith K Malhi Gin S GS Geddes John J Cipriani Andrea A
The Cochrane database of systematic reviews 20211008
<h4>Background</h4>Glutamergic system dysfunction has been implicated in the pathophysiology of bipolar depression. This is an update of the 2015 Cochrane Review for the use of glutamate receptor modulators for depression in bipolar disorder.<h4>Objectives</h4>1. To assess the effects of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with bipolar disorder. 2. To review the acceptability of ketamine and other glutamate receptor modulator ...[more]
Similar Datasets
Project description: Not available
| S-EPMC8434915 | biostudies-literature
Project description: Not available
| S-EPMC10524067 | biostudies-literature
Project description:The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine's antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine's adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine's antidepressant effects.
| S-EPMC4089991 | biostudies-literature
Project description:Established treatments for obsessive-compulsive disorder (OCD) are of benefit in approximately 3 of every 4 patients, but refractory disease remains distressingly common, and many treatment responders continue to experience considerable morbidity. This motivates a search for new insights into pathophysiology that may inform novel treatment strategies. Much recent work has focused on the neurotransmitter glutamate. Several lines of neurochemical and genetic evidence suggests that glutamate dysregulation may contribute to OCD, although much remains unclear. The off-label use of a number of pharmacological agents approved for other indications has been investigated in refractory OCD. We summarize investigations of memantine, riluzole, ketamine, D-cycloserine, glycine, N-acetylserine, topiramate, and lamotrigine. Evidence exists for benefit from each of these in some patients; though none has been proven effective with sufficient clarity to be considered part of standard care, these agents are options in individuals whose symptoms are refractory to better-established therapeutic strategies.
| S-EPMC4517847 | biostudies-literature
Project description:ObjectivePatents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine's ability to decrease symptoms of depression.MethodsThirty-six patients with anxious (n = 21) and non-anxious (n = 15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5 mg/kg) over 40 min. Post-hoc analyses compared changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14 days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of ≥ 7.ResultsA linear mixed model revealed a significant effect of anxiety group on the MADRS (p = 0.04) and HDRS (p = 0.04). Significant drug effects (all p < 0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p > 0.28).ConclusionsBoth anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine's novel role in the treatment of anxious bipolar depression.
| S-EPMC4431955 | biostudies-literature
Project description:Discerning distinct neurobiological characteristics of related mood disorders such as bipolar disorder type-II (BD-II) and unipolar depression (UD) is challenging due to overlapping symptoms and patterns of disruption in brain regions. More than 60% of individuals with UD experience subthreshold hypomanic symptoms such as elevated mood, irritability, and increased activity. Previous studies linked bipolar disorder to widespread white matter abnormalities. However, no published work has compared white matter microstructure in individuals with BD-II vs. UD vs. healthy controls (HC), or examined the relationship between spectrum (dimensional) measures of hypomania and white matter microstructure across those individuals. This study aimed to examine fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) across BD-II, UD, and HC groups in the white matter tracts identified by the XTRACT tool in FSL. Individuals with BD-II (n = 18), UD (n = 23), and HC (n = 24) underwent Diffusion Weighted Imaging. The categorical approach revealed decreased FA and increased RD in BD-II and UD vs. HC across multiple tracts. While BD-II had significantly lower FA and higher RD values than UD in the anterior part of the left arcuate fasciculus, UD had significantly lower FA and higher RD values than BD-II in the area of intersections between the right arcuate, inferior fronto-occipital and uncinate fasciculi and forceps minor. The dimensional approach revealed the depression-by-spectrum mania interaction effect on the FA, RD, and AD values in the area of intersection between the right posterior arcuate and middle longitudinal fasciculi. We propose that the white matter microstructure in these tracts reflects a unique pathophysiologic signature and compensatory mechanisms distinguishing BD-II from UD.
| S-EPMC8024340 | biostudies-literature
Project description:Current models of schizophrenia and bipolar disorder implicate multiple genes, however their biological relationships remain elusive. To test the genetic role of glutamate receptors and their interacting scaffold proteins, the exons of ten glutamatergic 'hub' genes in 1304 individuals were re-sequenced in case and control samples. No significant difference in the overall number of non-synonymous single nucleotide polymorphisms (nsSNPs) was observed between cases and controls. However, cluster analysis of nsSNPs identified two exons encoding the cysteine-rich domain and first transmembrane helix of GRM1 as a risk locus with five mutations highly enriched within these domains. A new splice variant lacking the transmembrane GPCR domain of GRM1 was discovered in the human brain and the GRM1 mutation cluster could perturb the regulation of this variant. The predicted effect on individuals harbouring multiple mutations distributed in their ten hub genes was also examined. Diseased individuals possessed an increased load of deleteriousness from multiple concurrent rare and common coding variants. Together, these data suggest a disease model in which the interplay of compound genetic coding variants, distributed among glutamate receptors and their interacting proteins, contribute to the pathogenesis of schizophrenia and bipolar disorders.
| S-EPMC3084736 | biostudies-literature
Project description:This paper focuses on depression that precedes an onset of manifest bipolar disorder as early stage bipolar disorder. First, we review how to pragmatically identify the clinical characteristics of patients presenting with an episode of depression who subsequently go on to develop episodes of mania or hypomania. The existing literature shows a strong consensus: accurate identification of depression with early onset and recurrent course with multiple episodes, subthreshold hypomanic and/or mixed symptoms, and family history of bipolar disorder or completed suicide have been shown by multiple authors as signs pointing to bipolar diagnosis. This contrasts with relatively limited information available to guide management of such "pre-bipolar" (pre-declared bipolar) patients, especially those in the adult age range. Default assumption of unipolar depression at this stage carries significant risk. Antidepressants are still the most common pharmacological treatment used, but clinicians need to be aware of their potential harm. In some patients with unrecognized bipolar depression, antidepressants can not only produce switch to (hypo)mania, but also mixed symptoms, or worsening of depression with an increased risk of suicide. We review pragmatic management strategies in the literature beyond clinical guidelines that can be considered for this at-risk group encompassing the more recent child and adolescent literature. In the future, genetic research could make the early identification of bipolar depression easier by generating informative markers and polygenic risk scores.
| S-EPMC7300293 | biostudies-literature
Project description:OBJECTIVES:Ketamine, an N-methyl d-aspartate (NMDA) antagonist, has rapid antidepressant effects in depressed subjects with bipolar disorder (BD). Evidence supports a role for the glutamatergic system in the pathophysiology of BD. This double-blind, randomized, cross-over study sought to determine cerebral metabolic correlates of antidepressant response to ketamine. METHODS:Twenty-one subjects with BD currently in a depressed state underwent [(18) F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging after receiving a placebo infusion as well as after receiving a ketamine infusion. Metabolism was compared between ketamine and placebo infusions, and correlated with clinical response. Regional metabolic rate of glucose (rMRGlu) in regions of interest (ROIs) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were the main outcome measures. RESULTS:The study found that change in metabolism between sessions was significantly correlated with percentage change in MADRS scores in the right ventral striatum; subjects who showed the greatest improvement had the largest metabolic increase after ketamine infusion compared to placebo. In a voxel-wise analysis, subjects with BD had significantly lower glucose metabolism in the left hippocampus following the ketamine infusion than following the placebo infusion. In addition, metabolism in the subgenual anterior cingulate cortex (ACC) following the placebo infusion was positively correlated with percentage improvement in MADRS score following the ketamine infusion. CONCLUSIONS:Taken together, the results suggest that higher activity in the subgenual ACC may predict antidepressant response to ketamine. Ketamine administration altered glucose metabolism in areas known to be involved in mood disorders; these alterations may partially underlie ketamine's mechanism of action.
| S-EPMC3949142 | biostudies-literature
Project description:BackgroundDysfunction of glutamate neurotransmission has been implicated in the pathology of schizophrenia and bipolar disorder, and one mechanism by which glutamate signalling can be altered is through RNA editing of ionotropic glutamate receptors (iGluRs). The objectives of the present study were to evaluate the editing status of iGluRs in the human prefrontal cortex, determine whether iGluR editing is associated with psychiatric disease or suicide and evaluate a potential association between editing and alternative splicing in the α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) iGluR subunits' pre-mRNA.MethodsWe studied specimens derived from patients with antemortem diagnoses of bipolar disorder (n = 31) or schizophrenia (n = 34) who died by suicide or other causes, and from psychiatrically healthy controls (n = 34) who died from causes other than suicide. The RNA editing at all 8 editing sites within AMPA (GluA2-4 subunits) and kainate (GluK1-2 subunits) iGluRs was analyzed using a novel real-time quantitative polymerase chain reaction assay.ResultsNo differences in editing were detected among schizophrenia, bipolar or control groups or between suicide completers and patients who died from causes other than suicide. The editing efficiency was significantly higher in the flop than in the flip splicoforms of GluA3-4 AMPA subunits (all p < 0.001).LimitationsThe study is limited by the near absence of specimens from medicationnaive psychiatric patients and considerable variation in medication regimens among individuals, both of which introduce considerable uncertainty into the analysis of potential medication effects.ConclusionWe found that iGluR RNA editing status was not associated with bipolar disorder, schizophrenia or suicide. Differences in editing between flip and flop splicoforms suggest that glutamate sensitivity of receptors containing GluA3 and/or GluA4 flop subunits is moderated as a result of increased editing.
| S-EPMC3380098 | biostudies-literature