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The Research On Ketamine Therapy

When it comees to evidence 95% of the reasearch showing that ketamine is effective in treating depression, anxiety, trauma and chronic pain was done with ketamine infusions. 

Treatment for Depression with Ketamine


Antidepressant effects of ketamine in depressed patients

This pioneering study was among the first to demonstrate the rapid antidepressant effects of ketamine. The randomized controlled trial found that a single subanesthetic dose of ketamine produced rapid and robust antidepressant effects in patients with treatment-resistant major depression. This study provided preliminary evidence for the potential of ketamine as a novel and rapid-acting treatment for depression, sparking further research in this area.

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

In this study, researchers examined the antidepressant effects of ketamine in patients with treatment-resistant major depression. The results revealed a significant improvement in depressive symptoms within hours of ketamine administration. These findings suggest that ketamine could present a novel and effective treatment for depression, especially in refractory cases. Moreover, the study contributes to our understanding of the potential of NMDA receptor antagonists as a new class of antidepressants, fostering hope for enhanced patient outcomes and reduced morbidity linked to traditional antidepressant medications.

Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression 

Participants in this study with treatment-resistant depression underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (0.5 mg/kg), administered three times weekly over a twelve day period. The overall response rate at the end of the study was 70.8%, with a significant mean decrease in Montgomery-Åsberg Depression Rating Scale score observed at two hours after the first ketamine infusion.

R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine

Intravenous ketamine, also known as generic or racemic ketamine, contains both the R and S forms of ketamine, while esketamine, administered in nasal form, only contains S-ketamine. In this study, R-ketamine demonstrated prolonged antidepressant effects whereas S-ketamine did not. This suggests that R-ketamine may offer greater potency and longer-lasting antidepressant effects compared to S-ketamine, highlighting the importance of both molecules rather than just one and emphasizing why IV ketamine is superior to the nasal alternative.

The effects of low‐dose ketamine on the prefrontal cortex and amygdala in treatment‐resistant depression

A hypoactive prefrontal cortex and a hyperactive amygdala, the region of the brain that plays a crucial role in processing emotions, particularly fear and other negative emotions, have been suggested to be associated with treatment-resistant depression. This study demonstrated rapid antidepressant effects of low-dose ketamine involving the activation of the prefrontal cortex with downregulation of the amygdala. These findings provide valuable insights into the neurobiological mechanisms underlying ketamine's antidepressant effects.

Treatment for suicidal ideations with ketamine

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression

This study suggests that a single ketamine infusion, adjunctive to ongoing pharmacotherapy, can significantly reduce suicidal ideation in depressed patients. The improvement persisted for at least 6 weeks. Adverse effects were mostly mild to moderate and transient. Follow-up assessments at 3 and 6 months showed no evidence of ketamine abuse.

Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide

In this trial, researchers evaluated the efficacy and safety of intranasal esketamine (a derivative of ketamine) in patients with treatment-resistant depression. The study found that esketamine produced rapid and significant antidepressant effects compared to placebo, leading to FDA approval of esketamine nasal spray for treatment-resistant depression in 2019.

Ketamine for acute suicidal ideation. An emergency department intervention

In this trial, depressed patients with acute suicidal ideation, requiring hospitalization, were given either intravenous ketamine or a saline placebo. At 90 minutes, 88% of the ketamine group achieved remission of suicidal ideation compared to 33% in the placebo group. No serious adverse events were reported. These findings suggest that ketamine is both safe and effective for rapidly reducing suicidal ideation in highly suicidal patients presenting to the emergency department.

Ketamine: an effective treatment for depression

Ketamine Enhances Visual Sensory Evoked Potential Long-term Potentiation in Patients With Major Depressive Disorder

Researchers investigated the mechanism of ketamine's antidepressant effects in this study. The results showed that 70% of participants experienced a significant reduction in depression symptoms after receiving ketamine, with evidence of changes in neural architecture modulation by ketamine. This study supports the hypothesis that ketamine's antidepressant effects may be mediated by enhancing


Efficacy of ketamine for major depressive episodes at 2, 4, and 6-weeks post-treatment

This meta-analysis aimed to assess the efficacy of ketamine in treating major depressive episodes beyond the standard 2-week observation period. The study found significant treatment effects at 2, 4, and 6 weeks post-administration, indicating that ketamine can be an effective pharmacological intervention for major depressive episodes, with effects lasting up to 6 weeks, and possibly longer for some individuals.

Ketamine Therapy has better outcomes when paired with psychotherapy and integration


Ketamine Assisted Psychotherapy - KAP


The systematic review suggest that the combination of ketamine and psychotherapy resulted in significantly greater improvements in depressive symptoms compared to either treatment alone. This suggests that integrating ketamine with psychotherapy could be a promising approach for addressing depression more comprehensively. Higher doses of ketamine, more frequent KAP sessions, and longer periods with psychotherapy appear to increase efficacy and durability of sustained improvements across various disorders. However, there is no one-size-fits-all approach, and tailoring interventions to individuals is essential.

Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression

In a large clinical trial involving 403 patients, researchers from Massachusetts General Brigham compared the effectiveness of subanesthetic intravenous ketamine to electroconvulsive therapy (ECT) for treatment-resistant depression. Ketamine outperformed ECT, the gold standard for treatment-resistant depression, with higher response and remission rates. Published in the New England Journal of Medicine, the study found that 55% of patients treated with ketamine experienced sustained improvement in depressive symptoms, without major side effects. This study, the largest of its kind, also assessed impacts on memory, a concern often associated with ECT. ECT can cause memory loss and other less-than desirable side effects. Ketamine, however, was not associated with significant side effects apart from transient dissociation and potential mild nausea during an infusion.

“People with treatment-resistant depression suffer a great deal, so it is exciting that studies like this are adding new options for them,” said Anand. “With this real-world trial, the results are immediately transferable to the clinical setting.”

Ketamine for the Treatment of Major Depression

This systematic review and meta-analysis compared the efficacy of racemic IV ketamine and nasal esketamine in treating depression. They analyzed 49 randomized controlled trials involving 3299 participants. Results showed that racemic ketamine generally had larger effects on depression severity, response, and remission rates compared to esketamine. Higher doses were more effective than lower doses, with differences observed in initial effects, ongoing treatment, and lasting effects after the final dose. The findings suggest that racemic ketamine may be more effective for depression treatment.

Clinical Outcomes of Intravenous Ketamine Treatment for Depression in the VA Health System

This study published in the Journal of Clinical Psychiatry included 215 Veterans who received six IV ketamine infusions resulting in significant symptom relief. The study suggests those who did experience improvements saw sustained benefits over at least 6 months with decreasing infusion frequency. Lead researcher Paul Pfeiffer underscores that while ketamine isn’t a “silver bullet,” its impact on previously treatment-resistant cases is remarkable.

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