A drug used as a general anaesthetic may also work as a remarkably rapid antidepressant, according to a preliminary study.

The drug’s hallucinogenic side effects mean it is unlikely to be prescribed to patients, but it could pave the way to new faster-acting antidepressants, the researchers suggest.

Ketamine is used as an animal tranquiliser, but is perhaps better known as an illicit street drug, sometimes called “special K”. Now researchers have found the drug can relieve depression in some patients within just 2 hours – and continue to do so for a week.

One problem with current antidepressants is that they typically take weeks to kick in. Some studies have found that patients may face a high risk of suicide in the first week after starting an antidepressant treatment because of this lag time. So researchers have been searching for alternative drugs.


Fast acting

In 2000, a small study of eight people with major depression suggested that ketamine mitigated depression to a certain degree (Biological Psychiatry, vol 47, p 351).

Carlos Zarate, chief of the Mood and Anxiety Disorders Research Unit at the National Institute of Mental Health in Bethesda, Maryland, US and colleagues, set out to conduct a larger, more detailed trial of the drug’s antidepressant effects.

They analysed data from 17 participants, all whom suffered from moderate to severe depression and had failed to respond to at least two types of conventional drug treatments.

In the first part of the experiment, the volunteers were given a single intravenous dose of either ketamine or a placebo. A week later, the participants were given the opposite treatment, unless the beneficial effects of the first intravenous dose were still evident. Depression improved within one day for 12 of the 17 who received ketamine. These patients showed a 50% reduction in their symptoms, according to the Hamilton Depression Rating Scale.

In previous trials for established, long-acting antidepressants, only 63% of participants saw this same reduction in symptoms after eight weeks of medication.

Lasting effect

Overall, while nine of the 17 patients had a 50% reduction in their depression within the first 2 hours of ketamine treatment, only one person receiving the placebo experienced the same effect in this period of time.

The antidepressant effects of ketamine lasted for a week in four people and at least two weeks in another two subjects. “We didn’t believe it would last that long,” says Zarate.

Most anti-depressants work by boosting levels of the brain chemical serotonin. But ketamine acts in a different way, by reducing the effects of another neurotransmitter, called glutamate. This may explain the drug’s faster action, and suggest an alternative pathway for other antidepressant drugs, the researchers say.

Trails of light

However, one of the reasons that clubbers abuse ketamine is for its hallucinogenic properties, such as seeing trails of light, and this was one of the most significant side effects occurring in the “vast majority” of participants, Zarate says.

The hallucinations will also have revealed to patients in the trial when they had received ketamine, rather than an inert placebo. This knowledge could have made them more likely to report a positive response than to the placebo.

Zarate is currently exploring compounds derived from ketamine to see if they can find one that has antidepressant effects without causing hallucinations.

Journal reference: Archives of General Psychiatry (v 63, p 856)