Study: Ketamine use for depression produces common but transient side-effects

New research published in Lancet Psychiatry examined the frequency of side-effects associated with the use of ketamine to treat depression. The study found that acute side-effects associated with a single-dose treatment are common, but they are generally transient.

“I was interested in this topic because of the amazing results reported for the effects of ketamine in treating depression,” explained corresponding author Colleen K. Loo, a psychiatrist and clinical academic researcher of the University of New South Wales.

Several studies have found that a single dose of ketamine produces an antidepressant effect in patients with treatment-resistant major depressive disorder. The drug is already medically approved for use as an anaesthetic.

“Ketamine was highly effective and worked incredibly quickly i.e. in about a day, whereas we expect most antidepressant treatments would take weeks to work. I didn’t know whether to believe these results and decided to commence this research myself in 2012.”

“I think the key messages now are: ketamine has potential to be a major breakthrough in the treatment of depression,” Loo told PsyPost. “This is because it can be highly effective even where other treatments have failed and it can work very rapidly. It is more powerful than other treatments I have seen for depression, except for maybe electroconvulsive therapy.

“It appears to be as effective as electroconvulsive therapy. However, the effectiveness and safety of ketamine need to be further evaluated in research trials before we can recommend its general clinical use for the treatment of depression.”

Loo and her colleagues conducted a systematic analysis of 60 prior studies on the use of ketamine to treat depression, which included 899 patients in total.

The most common side-effects were anxiety, headache, dizziness, dissociation, elevated blood pressure, and blurred vision. However, most side-effects spontaneously resolved shortly after ketamine was administered.

But whether ketamine could have long-lasting antidepressant effects is still unclear.

“While a single treatment has been shown in multiple proof-of-concept studies to induce powerful and rapid antidepressant effects, often these wear off after a few days,” Loo said. “The next step has been to apply multiple treatments in a course of ketamine treatments, with the aim of achieving a longer term improvement.”

Previous research, however, has found that chronic ketamine use is linked to more severe side-effects, such as hepatotoxicity, cognitive deficits, and addiction.

Loo said there are two main questions that scientists still need to answer.

“First, does a course of treatments lead to lasting improvement?” she explained. “Second, what is the safety of giving ketamine repeatedly?”

“In a recent meta-analysis which examined all the reports of safety outcomes from clinical trials giving ketamine for depression, we found that the short term effects of ketamine (on blood pressure perception, feeling) had been reasonably well studied and characterised. However the effects of repeated treatments and longer term effects had been minimally studied and there is insufficient data on this. Therefore I think it is prudent for us to examine the effectiveness and safety of repeated treatments further, before we embark on using it as a clinical treatment.”

The study, “Side-effects associated with ketamine use in depression: a systematic review“, was also co-authored by Brooke Short, Joanna Fong, Veronica Galvez, and William Shelker.