Single dose of ketamine reduces anhedonia in those with treatment-resistant depression

Ketamine may be able to treat anhedonia in patients with depression, according to a new study published in the Journal of Psychopharmacology.

Anhedonia is the inability to desire or find enjoyment in pleasurable activities. It is associated with severe, treatment-resistant forms of major depressive disorder (MDD) and is a reliable predictor for suicide. However, experts have had little success battling it.

“Despite the importance of this symptom in psychiatry, and particularly in MDD, there is currently no medication specifically targeting anhedonia,” said Niall Lally, PhD student at University College London and corresponding author.

Fifty-two individuals participated in the study, which was conducted at the National Institute of Mental Health in Bethesda, Maryland. The participants were all medication-free; currently experiencing a major depressive episode; and considered “treatment-resistant,” meaning they had experienced at least two failed antidepressant trials.

The participants received an infusion of ketamine, a glutamate-based antidepressant, over a period of 40 minutes. They were then randomized and given either riluzole (another glutamate-based drug) or a placebo in daily doses. Scientists found that participants reported significantly lower levels of anhedonia for up to three days after the ketamine infusion. However, the daily dose of riluzole had little effect.

“Ketamine rapidly reduced levels of anhedonia in this sample, with a substantial effect within 40 minutes that remained 3 days post-infusion,” the researchers wrote.

A PET brain scan of 20 participants suggested the decrease in anhedonia was caused by changes in the hippocampus, dorsal anterior cingulate cortex, and orbitofrontal cortex. However, the results, “while promising, remain tentative due to the lack of a placebo-controlled comparison for the effects of ketamine,” Lally and his colleagues cautioned.

Though the study was preliminary, the team believes it could bring hope for those who suffer from treatment-resistant depression.

“Our results add increasing weight to the promise of [ketamine and similar drugs]in treating cardinal symptoms of depression,” said Lally. “Given the safety of ketamine, the potential for treating patients with residual anhedonic symptomatology is high.”