The drug ketamine may have moved a step closer to routine use as an antidepressant. Positive – if modest – results from a large trial of an intranasal spray based on ketamine were announced by pharmaceutical giant Janssen today.
The firm is developing the treatment for people with severe depression . If everything goes to plan, the medicine could be available next year in the US and Europe.
Ketamine has long been used as an anaesthetic in people and animals. Some people also take it as a recreational drug, with similar effects to LSD and magic mushrooms. It makes people hallucinate and light-headed, although too much can send them into a “k-hole” – where they can’t talk or move.
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When depressed people are given a low-dose infusion of ketamine, after the euphoria wears off, some report immediate changes in their mood, and lifting of suicidal thoughts. In contrast, existing antidepressants usually take several weeks to kick in.
Small improvement
Animal studies suggest ketamine triggers the release of a chemical called BDNF, which tells . Other studies have suggested this may be how physical exercise helps ward off depression.
Although not yet approved for this use, a few centres offer ketamine as an intravenous drip for people with severe depression, as an experimental treatment. It should only be given in this way by clinics that have an anaesthetist and resuscitation equipment on hand, in case the person has a bad reaction, says of Newcastle University.
That might change, following the announcement of promising results from a large trial of a nasal spray of esketamine – the most potent isomer of ketamine – at a meeting of the in New York.
The trial involved people who had not responded to at least two other depression treatments. Each person was given a new formulation of a standard antidepressant, plus either the esketamine nasal spray or a placebo, inert nasal spray. Compared with the control group, the esketamine group showed an average improvement of four points on a 54-point depression scale after four weeks of treatment.
The results are less impressive than were hoped for – but may well be enough to get the drug approved by regulatory agencies, says McAllister-Williams. “I’m slightly disappointed. But they are giving me confidence that it works.”
More trials
In a second trial in elderly people with treatment-resistant depression, there was a fall of 3.6 points on the depression scale compared with the placebo group, but this wasn’t enough to be statistically significant. Janssen will probably need positive results from at least one further large trial to get the treatment approved. Three other trials are still underway.
It’s currently unclear how often a person might need to use the nasal spray to keep depression at bay. In the trials, participants used the nasal spray twice a week for four weeks, then gradually took fewer doses.
However, experimental use in the clinic has generally been less frequent, such as one infusion every few months or so.
Depression re-think
It is important to get the dosing right, and work out how long it is safe to take ketamine for. , a psychiatrist at the Hergest Unit in Bangor says long-term use may raise the risk of bladder shrinkage, which has been seen in people who take a lot of ketamine recreationally.
Because ketamine seems to work in a different way to existing treatments for depression, it may lead to a re-think of what causes the condition. Antidepressants like Prozac boost levels of signaling molecules such as serotonin in the brain, so for several decades it was thought that a lack of these compounds is what causes depression. But several studies have questioned this “chemical imbalance” theory.
Some hope that if a form of ketamine does become licensed for depression, it will help add legitimacy to this form of treatment. “I want more people to know about this,” says James [not his real name], who has had depression and anxiety since his teenage years.
Last year, despite being on two medications, James was having recurrent thoughts of suicide. But after a ketamine infusion, these intrusive thoughts went away. “It was like there was radio silence, clear skies,” he says. “I felt totally normal for the first time in decades.”
