Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression

Salloum, Naji C.; Fava, Maurizio; Freeman, Marlene P.; Flynn, Mary M.; Hoeppner, Bettina B.; Hock, Rebecca S.; Cusin, Cristina; Iosifescu, Dan V.; Trivedi, Madhukar H.; Sanacora, Gerard; Mathew, Sanjay J.; DeBattista, Charles; Ionescu, Dawn F.; Papakostas, George I.

doi:10.1002/da.22875

Cited by 39 publications

(27 citation statements)

References 29 publications

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“…Significant reductions in overall depressive symptom severity, as measured by QIDS-SR 16 scores, were seen in both the anxious-distress and low–anxious distress groups with greater reductions observed in the anxious-distress group.We also observed a significant and sustained reduction in SI with IV ketamine treatment in both the anxious-distress and low–anxious distress groups. Anxiety symptoms also significantly reduced in patients with anxious depression, a finding that aligns with extant studies (Ionescu et al, 2015; Salloum et al, 2019; Wang et al, 2019).…”

Section: Discussionsupporting

confidence: 88%

“…Ketamine is an N-methyl-D-aspartate receptor antagonist shown to provide rapid antidepressant effects in patients with TRD (aan het Rot et al, 2010; Coyle and Laws, 2015; Feifel et al, 2017; Murrough et al, 2013; Phillips et al, 2019). Moreover, available evidence from controlled clinical trials suggests that ketamine is effective in treating symptoms of anxiety as well as anxious depression (Ionescu et al, 2015; Salloum et al, 2019). However, it has been reported that patients who enroll in clinical trials may not be representative of persons receiving care in clinical practice (Lorenzo-Luaces et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence

et al. 2020

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Background: Individuals meeting criteria for treatment-resistant depression (TRD) are differentially affected by high levels of anxiety symptoms. Aims: There is a need to identify the efficacy of novel rapid-onset treatments in adults with mood disorders and comorbid anxious-distress. Methods: This study included patients with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD) who were receiving intravenous (IV) ketamine treatment at a community-based clinic.Anxious-distress was proxied using items from the Quick Inventory of Depressive Symptomatology–Self Report 16-item (QIDS-SR16) and Generalized Anxiety Disorder 7-item (GAD7) scales. The difference in QIDS-SR16 total score, QIDS-SR16 suicidal ideation (SI) item and GAD7 score were analyzed between groups. Results: A total of 209 adults with MDD ( n = 177) and BD ( n = 26) were included in this analysis. From this sample, 94 patients (mean = 45 ± 13.9 years) met the criteria for anxious-distress. Individuals meeting the criteria for anxious-distress exhibited a significantly greater reduction in QIDS-SR16 total score following four infusions ( p = 0.02) when compared with patients not meeting the anxious-distress criteria. Both anxious-distressed and low-anxiety patients exhibited a significant reduction in SI ( p < 0.0001) following four infusions.Finally, there was a significantly greater reduction in anxiety symptoms in the anxious-distress group compared with the non–anxious distress group following three ( p = 0.02) and four infusions ( p < 0.001). Conclusion: Patients with TRD and prominent anxiety receiving IV ketamine exhibited a significant reduction in depressive, SI and anxiety symptoms.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence

et al. 2020

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“…It derived from phencyclidine (PCP) and is designed to alleviate the serious psychosis/psychotic side effects and potential abuse of maternal drugs 2. In recent years, ketamine has been found to have potential therapeutic uses in pain management, neurology, and psychiatry 3–6. Low-dose intravenous ketamine can reduce perioperative opioid consumption and can provide chronic postsurgical pain relief for patients 7,8.…”

Section: Introductionmentioning

confidence: 99%

<p>Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study</p>

Wang

Huang

Yang

et al. 2019

DDDT

119

111

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PurposeTo assess the pharmacokinetics and safety of pure S-ketamine (esketamine) in Chinese patients undergoing painless gastroscopy and evaluate the potential advantage of esketamine in clinical treatment compared with racemate ketamine hydrochloride injection.Patients and methodsA randomized, open-label, parallel-controlled, Phase I study was performed with 32 patients undergoing painless gastroscopy. Patients received a single dose of esketamine (0.5 mg/kg) or racemic ketamine (1 mg/kg, esketamine:R-ketamine=1:1), injected in 10 s. Blood samples were collected for pharmacokinetic analysis. The concentrations of esketamine, R-ketamine, S-norketamine, and R-norketamine were measured with a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.ResultsAfter administering a single dose of esketamine and racemate ketamine, the pharmacokinetics parameters of esketamine and S-norketamine are both similar in treatment groups. The clearance of esketamine in two groups was 18.1±3.2 and 18.4±3.4 mL/min•kg, respectively. However, in the ketamine group, esketamine has a larger clearance than R-ketamine (18.4±3.4 mL/min·kg vs 15.8±3.1 mL/min·kg, P<0.001). Further analysis showed that gender did not affect the pharmacokinetics of esketamine and racemate ketamine. Regarding the safety of esketamine and racemate ketamine, no serious adverse events were observed during treatment, and the incidences of adverse events were 75.0% (esketamine) and 87.5% (racemate ketamine). The main adverse reactions were dizziness, agitation, nausea, vomiting, headache, and fatigue. However, compared with racemic ketamine, esketamine offers a shorter recovery time (9 mins vs. 13 mins, P<0.05) and orientation recovery time (11.5 mins vs. 17 mins, P<0.05) after short anesthesia.ConclusionEsketamine administration as a single dose of 0.5 mg/kg was generally safe and tolerated in patients undergoing painless gastroscopy. In terms of anesthesia, a relatively small dose of esketamine can be used instead of racemate ketamine for routine treatment without consideration of gender differences.

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“…112 However, a recent study found no difference in the response to ketamine infusion between patients with anxious and non-anxious depression. 113 More research on the predictors of ketamine treatment response in patients with MDD is still needed.…”

Section: Predictor Of Response To Ketaminementioning

confidence: 99%

Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives

Shin

Kim

2020

Psychiatry Investig

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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.

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Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression

Cited by 39 publications

References 29 publications

The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence

The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence

<p>Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study</p>

Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives

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