Ketamine antidepressant effect

Ketamine, an injectable anesthetic that has been shown to exert a rapid but short-lived antidepressant effect, may reduce suicidal ideation independently of a reduction in depressive symptoms, new research suggests.

Investigators at the National Institute of Mental Health in Bethesda, Maryland, distinguished the relationship of ketamine to reduced suicidal thoughts from its effect on depression and anxiety symptoms across 4 studies conducted in patients with treatment-resistant major or bipolar depression.

Although the reduction of suicidal ideation was correlated with improvements in mood, this new analysis showed that changes in mood and anxiety accounted for no more than 19% of the improvements on suicidal measures, including the Scale for Suicide Ideation items of the “wish to live” and “wish to die.”

The study is “a first step in exploring how ketamine may impact suicidal thoughts, whether through depressive or anxiety symptoms,” lead investigator Elizabeth Ballard, PhD, told Medscape Medical News.

The study was published online August 12 in the Journal of Psychiatric Research.

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An N-methyl-D-asparate (NMDA) glutamate receptor antagonist, ketamine has made headlines in recent years because several studies have shown that it produces a rapid antidepressant effect in patients with unipolar and bipolar depression when delivered intravenously and, most recently, intranasally in spray form.

In addition, a recent study published in JAMA Psychiatry and reported by Medscape Medical News also suggests it may be a rapid treatment for posttraumatic stress disorder.

The researchers point out that suicide is a psychiatric emergency and that there are no approved medications to effectively treat suicidal ideation, noting that antidepressants can take weeks or months before they take effect.

“As a consequence, the 400,000 individuals who seek emergency treatment for suicidal thoughts and behavior each year often do not receive timely relief,” the authors write.

Although it is known that ketamine has a rapid effect on depression and anxiety as well as suicidal thoughts, it is not clear whether this effect is independent or is a consequence of a reduction in depressive and anxiety symptoms.

An agent with rapid and specific effect on suicidal ideation might serve not only as an immediate intervention prior to the onset of antidepressants but also as an alternative pharmacologic model to lithium or clozapine, which, the researchers suggest, exert antiaggressive and anti-impulsive effects that “may be more suited to reducing suicide attempts than suicidal ideation.”

To evaluate ketamine’s effect on suicidal ideation, the investigators analyzed data from 4 independent, previously published clinical trials investigating the use of ketamine in 133 patients aged 18 to 65 years with treatment-resistant depression (major depressive disorder or bipolar depression), including a subset of 57 patients determined to have suicidal thoughts at baseline.

The investigators evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale, the Scale for Suicidal Ideation, the Beck Depression Inventory, and the Hamilton Anxiety Rating Scale.

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