Conference Coverage

Ketamine curbs suicidal ideation independent of antidepressant effect


 

AT THE ECNP CONGRESS

– Repeated infusions of ketamine appear to have a direct effect in quelling suicidal ideation independent of the drug’s impact on depressive symptoms, Pierre Blier, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

“Our preliminary results indicate that ketamine reduced suicidal ideation even in patients who failed to show a reduction in depression severity with repeated infusions,” observed Dr. Blier, professor of psychiatry at the University of Ottawa.

If the findings from this proof-of-concept study are confirmed, it would be very good news indeed.

“Suicidal ideation often requires rapid intervention, but there are very few treatments that are effective in reducing suicidal ideation, and none are fast acting,” the psychiatrist noted.

Therapeutic interest in ketamine is running high because subanesthetic doses of the drug have been shown to reduce depressive symptoms within a matter of hours, albeit transiently, in patients with treatment-resistant depression. If the drug acts as quickly in decreasing suicidal ideation as it does for depression, it would have major implications for clinical practice. An estimated 1 million people die each year worldwide from suicide, and two-thirds of them have major depressive disorder.

Dr. Blier reported on 27 patients with treatment-resistant depression, defined as failure to respond to at least two antidepressant medications from different pharmacologic classes at adequate dosages for at least 6 weeks each, along with two augmentation strategies. Their mean baseline score on the Montgomery-Asberg Depression Rating Scale (MADRS) was roughly 35. Five of the 27 had made one or more prior suicide attempts. Twenty-six of the 27 had suicidal ideation at baseline as defined by a MADRS suicidal ideation score (MADRS-SI) of more than 0. The MADRS-SI is based upon item 10 on the MADRS and is scored 0-6. Eight patients reported marked suicidal ideation as defined by a baseline MADRS-SI score of 4 or higher.

Study participants received a total of seven intravenous infusions of ketamine over roughly 3 weeks. Patients were retested 2-3 days after the seventh infusion, at which time 16 patients were categorized as treatment responders on the basis of at least a 50% reduction in their total MADRS score. Indeed, they averaged a 20.7-point reduction in the non–suicide-related MADRS score – that is, items 1-9, which reflect symptoms of depression – compared with a mere 3.9-point decrease in the 11 ketamine nonresponders. This 59% response rate for depressive symptoms is consistent with reported results of other studies of ketamine in patients with treatment-resistant depression, according to Dr. Blier, also professor of cellular/molecular medicines at the university.

The baseline MADRS-SI score averaged 2.9 in treatment responders and was similar at 2.5 in the nonresponders. But after seven infusions of ketamine, 21 of 27 patients had a MADRS-SI score of 0 or 1. The key study finding was that both the ketamine responders and nonresponders in terms of depressive symptoms experienced significant reductions in suicidal ideation. The 16 responders averaged a 2.4-point decrease from baseline in MADRS-SI scores, while the 11 nonresponders averaged a 1.5-point reduction. The magnitude of the reduction in MADRS-SI was significantly greater in the antidepressant responders than the nonresponders, but the improvement in suicidal ideation was statistically significant and clinically meaningful in both groups.

Seven of the 8 patients with baseline marked suicidal ideation and a MADRS-SI of 4 or greater improved to a score of 2 or less after their seven ketamine infusions, meaning they were having at most only fleeting suicidal thoughts.

Dr. Blier and coinvestigators are now expanding the ketamine study, enrolling up to 40 additional patients with treatment-resistant depression and suicidality in order to confirm the preliminary findings.

Dr. Blier reported having no financial conflicts of interest regarding this study, which was funded by the Canadian Institutes of Health Research. He noted that he receives research grants from and/or serves on advisory boards for more than a dozen pharmaceutical companies.

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