Small-Dose Ketamine Improves the Postoperative State of Depressed Patients

Kudoh, Akira; Takahira, Yoko; Katagai, Hiroshi; Takazawa, Tomoko

doi:10.1097/00000539-200207000-00020

Cited by 174 publications

(112 citation statements)

References 19 publications

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“…Beside the abovementioned report on D-cycloserine, slight antidepressant effects in humans have also been observed with the NMDA receptor antagonists amantadine 10,11 and ketamine. 12,13 Riluzole, an antiglutamatergic agent believed to increase the glutamatergic uptake into the astrocytes, is under intensive investigation for its antidepressant potential. 14 A recent series of openlabelled studies and case reports demonstrated its efficacy.…”

Section: Glutamate In Depressionmentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-c, or tumor necrosis factor-a activate the tryptophan-and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes -counteracting this metabolism due to the lack of an enzyme of this metabolism -have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid. Molecular Psychiatry (2007) 12, 988-1000; doi:10.1038/sj.mp.4002006; published online 24 April 2007 Keywords: major depression; psychoneuroimmunology; IDO; glutamate; immune system; serotonin Glutamate in depressionGlutamatergic neurotransmission is involved in depression and interacts with the serotonergic and noradrenergic systems The common therapeutic mechanism of antidepressant drugs is the enhancement of serotonergic and/or noradrenergic neurotransmission. On the basis of this pharmacological profile of antidepressant drugs, neurochemical research on major depression ...

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Section: Glutamate In Depressionmentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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“…[18][19][20][21][22][23][24][25][26][27][28][29][30][31] Other than two case reports, [32][33][34] no studies to date have examined ketamine's role in treating depression or anxiety in the hospice population. To our knowledge, no investigations of depression treatment for any population have been carried out with oral ketamine, and only a couple investigations of ketamine have assessed symptoms of anxiety.…”

Section: Introductionmentioning

confidence: 99%

Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Irwin

Iglewicz

Nelesen

et al. 2013

Journal of Palliative Medicine

138

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Background: Depression and anxiety are prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine has many properties that make it an interesting candidate for rapidly treating depression and anxiety in patients receiving hospice care. To test this hypothesis, a 28-day, open-label, proof-of-concept trial of daily oral ketamine administration was conducted in order to evaluate the tolerability, potential efficacy, and time to potential efficacy in treating depression and anxiety in patients receiving hospice care. Methods:In this open-label study, 14 subjects with symptoms of depression or depression mixed with anxiety warranting psychopharmacological intervention received daily oral doses of ketamine hydrochloride (0.5 mg/ kg) over a 28-day period. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS), which was used to rate overall depression and anxiety symptoms at baseline, and on days 3, 7, 14, 21, and 28. Results: Over the 28-day trial there was significant improvement in both depressive symptoms (F 5,35 = 8.03, p = 0.002, g 2 = 0.534) and symptoms of anxiety (F 5,35 = 14.275, p < 0.001, g 2 = 0.67) for the eight subjects that completed the trial. One hundred percent of subjects completing the trial responded to ketamine for both anxiety and depression. A significant response in depressive symptoms occurred by day 14 for depression (mean D = 3.5, d = 1.14, 95% CI = 1.09-5.9, p = 0.01) and day 3 for anxiety (mean D = 2.4, d = 0.67, 95% CI = 1.0-3.7, p = 0.004). These improvements remained significant through day 28 for both depression (mean D = 4.0, d = 1.34, 95% CI = 2.3-5.9, p = 0.001) and anxiety (mean D = 6.09, d = 1.34, 95% CI = 3.6-8.6, p < 0.001). Side effects were rare, the most common being diarrhea, trouble sleeping, and trouble sitting still. Conclusions: Patients who received daily oral ketamine experienced a robust antidepressant and anxiolytic response with few adverse events. The response rate for depression is similar to those found with IV ketamine; however, the time to response is more protracted. The findings of the potential efficacy of oral ketamine for depression and the response of anxiety symptoms are novel. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the efficacy and safety of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care or other subject populations.

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“…13,14 There is also a growing body of literature supporting the rapid treatment of depressive symptoms with intravenous (IV) ketamine. [15][16][17][18][19][20][21] A single case using IV ketamine to treat depression in a patient with advanced cancer has been reported. 22 No studies to date have examined ketamine's role in treating depression in the hospice population.…”

Section: Introductionmentioning

confidence: 99%

Oral Ketamine for the Rapid Treatment of Depression and Anxiety in Patients Receiving Hospice Care

Irwin

Iglewicz

2010

Journal of Palliative Medicine

105

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Depression is prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Here, two cases are reported in which a single oral dose of ketamine provided rapid and moderately sustained symptom relief for both depression and anxiety. In addition, no adverse effects were noted. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the effectiveness of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care. Ketamine may be a promising safe, effective, and cost-effective rapid treatment for depression and anxiety in this population.

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Small-Dose Ketamine Improves the Postoperative State of Depressed Patients

Cited by 174 publications

References 19 publications

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Oral Ketamine for the Rapid Treatment of Depression and Anxiety in Patients Receiving Hospice Care

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