Ketamine could be used as an antidepressant in the future. WikiComms

Ketamine has been shown to have powerful antidepressant properties, but the long-term risks of taking the drug are still unclear. Scientists warn that this issue must be addressed, if ketamine is to be widely adopted as a treatment for depression.

This is the world-first systematic review into the safety of ketamine as a treatment for depression, published in the Lancet Psychiatry. Researchers reviewed previous published studies of ketamine as a treatment for depression.

Most showed impressive results, with patients that had hard-to-treat depression reporting that their symptoms had improved after just a short course of the drug.

However, only a few effectively looked at the safety of repeated doses or sustained use of ketamine. This is problematic, because any ketamine treatment for depression would have to be taken regularly over a long period of time.

"Despite growing interest in ketamine as an antidepressant, and some preliminary findings suggesting its rapid-acting efficacy, to date this has not been effectively explored over the long term and after repeated dosing," said co-author Colleen Loo, from the Black Dog Institute in Australia.

"As ketamine treatment will likely involve multiple and repeated doses over an extended time period, it is crucial to determine whether the potential side effects outweigh the benefits to ensure it is safe for this purpose."

Side effects after one dose

In the study, Loo and colleagues analysed 60 studies encompassing a total of 899 patients who had received at least one dose of ketamine.

They discovered that acute side effects were commonly reported by researchers after they assessed the effects of a single treatment of ketamine, but there was little follow-up to monitor them.

The author of the new study noted that side effects were more likely to occur when ketamine was given intravenously, and were usually reported on immediately following a single dose. There was no conclusive data available regarding ketamine's longer-term or cumulative effects.

Among the most common side effects were headache, dizziness, dissociation, elevated blood pressure and blurred vision. These side effects are similar to the ones reported by patients who take ketamine for chronic pain or by recreational users of party drug ketamine – perhaps better known as 'special K'.

"Our study also raises questions over the risk of administering ketamine in patients with pre-existing or co-morbid medical conditions, such as those with a history of high blood pressure or heart disease," Loo pointed out.

"For instance, we know that when used to treat chronic pain, ketamine is associated with acute blood pressure changes, and experts recommend lower doses administered through slower-acting, non-intravenous means accordingly."

The authors conclude that despite ketamine looking promising as a treatment for depression, larger clinical trials are urgently needed. They will have to focus on assessing the safety of repeated dosing regimes, consider co-morbid physical health factors and actively assess and report on potential side effects.