Archives of General Psychiatry
August 1, 2010
Nancy Diazgranados, Lobna Ibrahim, Nancy E. Brutsché et al.
969 citations
A single intravenous dose of ketamine, an N-methyl-D-aspartate-receptor antagonist, produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. Depressive symptoms improved within 40 minutes and remained significantly better than placebo through day 3. The largest drug effect occurred at day 2. Seventy-one percent of subjects responded to ketamine versus 6% to placebo. One subject in each group developed manic symptoms. Ketamine was generally well tolerated, with dissociative symptoms only at the 40-minute point.
The Journal of Clinical Psychiatry
July 13, 2010
Nancy Diazgranados, Lobna Ibrahim, Nancy E. Brutsché et al.
563 citations
A single infusion of ketamine (0.5 mg/kg) rapidly reduced suicidal thoughts in people with treatment-resistant major depression. Suicidal ideation scores dropped significantly within 40 minutes and remained lower for at least 4 hours. Among the 10 participants who had a score of 4 or higher on the Scale for Suicide Ideation at the start, all dropped below 4—9 within 40 minutes and 1 by 80 minutes. Depression, anxiety, and hopelessness also improved substantially at all measured time points. The findings suggest ketamine may offer a fast-acting intervention for suicidal ideation, a medical emergency with few pharmacologic options.
Harvard Review of Psychiatry
August 1, 2010
Carlos A. Zarate, Rodrigo Machado‐Vieira, Ioline D. Henter et al.
226 citations
Mood disorders like bipolar disorder and major depressive disorder are common, chronic, and recurrent, affecting millions worldwide. Existing antidepressants and mood stabilizers are insufficient for many, with low remission rates, delayed action, residual symptoms, and relapses. New therapeutic agents with faster and sustained effects are urgently needed. The glutamatergic system has been implicated in the pathophysiology of these disorders, with evidence confirming the role of modulators riluzole and ketamine as proof-of-concept agents. Trials with diverse glutamatergic modulators are underway, and this system holds promise for developing next-generation therapeutics.
British Journal of Clinical Pharmacology
February 1, 2012
Xiaochen Zhao, Swarajya Lakshmi Vattem Venkata, Ruin Moaddel et al.
136 citations
Ketamine is metabolized into several compounds, and this study shows that norketamine is not the main metabolite circulating in the blood after a single 40-minute infusion of 0.5 mg/kg ketamine in patients with treatment-resistant bipolar depression. Instead, dehydronorketamine was the major metabolite in four out of nine patients, norketamine in three, and hydroxynorketamine in two. Large inter-patient variation in metabolite levels was observed. The findings suggest that future research on ketamine's effects should measure these downstream metabolites.
The International Journal of Neuropsychopharmacology
November 1, 2011
Giacomo Salvadore, Jan Willem van der Veen, Yan Zhang et al.
105 citations
Pretreatment levels of certain amino-acid neurotransmitters in the prefrontal cortex predict how well patients with major depressive disorder respond to a single intravenous infusion of ketamine. In fourteen drug-free patients, a lower ratio of glutamine to glutamate in the dorsomedial/dorsal anterolateral prefrontal cortex was associated with greater improvement in depressive symptoms 230 minutes after ketamine administration. Higher glutamate levels in the ventromedial prefrontal cortex correlated with greater improvement in anxiety symptoms. The findings suggest that the presence of reduced glial cells, reflected by the lower glutamine-to-glutamate ratio, may indicate which patients are more likely to benefit from ketamine treatment.
Bipolar Disorders
September 18, 2013
Allison C. Nugent, Nancy Diazgranados, Paul J. Carlson et al.
86 citations
In people with bipolar disorder who are depressed, a single ketamine infusion alters brain glucose metabolism in regions linked to mood disorders. Those who improved most showed the largest metabolic increase in the right ventral striatum. Ketamine also lowered metabolism in the left hippocampus compared with placebo. Higher baseline activity in the subgenual anterior cingulate cortex predicted a stronger antidepressant response to ketamine. These metabolic changes may help explain how ketamine works.
Bipolar Disorders
September 14, 2012
David A. Luckenbaugh, Lobna Ibrahim, Nancy E. Brutsché et al.
69 citations
In people with bipolar depression, those who have a first-degree relative with alcohol dependence show a greater and more sustained antidepressant response to a single low dose of ketamine than those without such a family history. The study also found that individuals with a positive family history experienced fewer psychosis-like and dissociative side effects after ketamine infusion. These findings suggest that family history of alcohol dependence may help predict who benefits most from ketamine treatment and should be considered when developing new glutamatergic therapies for depression.