This Month in Psychopharmacology

Ketamine's Antidepressant Mechanism Linked to the Opioid System?

In the new study, the researchers hypothesized that ketamine works to treat depression at least in part by activating opioid receptors. Researchers gave participants the opioid-blocking drug naltrexone before they underwent ketamine treatment. No studies to date have directly addressed the role of opioid receptors in ketamine’s antidepressant effects.

The study included 12 participants diagnosed with recurrent major depressive disorder who had tried = four antidepressants or other depression treatments but hadn't benefited from them. All 12 patients received ketamine two infusions. Placebo or naltrexone was administered 45 minutes before ketamine infusion and ketamine was administered by intravenously over 40 minutes. One month later, patients received another ketamine infusion after receiving a placebo or naltrexone.

Results from the study found that when participants received ketamine with the placebo, they experienced a dramatic reduction in their symptoms of depression, but when they received naltrexone, the ketamine had almost no effect on their symptoms of depression. Patients who received naltrexone still experienced "dissociative effects" from ketamine, such as hallucinations.

More research is needed to examine whether ketamine's antidepressant effects are due to its actions on opioid receptors alone, its combined effect on opioid and glutamate receptors, or another mechanism. If ketamine does indirectly activate opioid receptors, it could even have positive effects in approaching the opioid as well as the other epidemics.

Reference:

Williams NR, Heifets BD, Blasey C, et al. Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism. Am J Psychiatry. 2018; Epub ahead of print. Abstract



For more information on novel antidepressants:

2018 NEI Congress, November 7–11, Orlando, FL
More Than Monoamines: A Look at Novel Antidepressants
How Might Ketamine Work for Treatment-Resistant Depression? (Member-only CME animation)