A nasal spray could be a new way to tackle depression. Based on a horse tranquilliser, the spray gets to work in as little as two hours, far quicker than widely used medications that can take weeks to kick in.
The liquid contains a compound called esketamine, which is thought to act on the brain chemical glutamate to restore connections between brain cells. It's used in far smaller doses than the street drug ketamine.
The U.S. regulator, the Food and Drug Administration, last week approved the use of the spray for patients with depression that does not respond to other treatments.
Five UK centres are taking part in a long-term trial of the spray, which is used twice a week. Depression is a mood disorder that causes persistent feelings of sadness and loss of interest. Clinical depression is estimated to affect one in 15 adults at some time.
It is the result of changes in brain chemistry, and causes range from genetics and changes in hormone levels, to chronic medical conditions, stress and grief.
The most common treatments are drugs called selective serotonin reuptake inhibitors (SSRI). These work for some — not all — patients, and can take between two and six weeks to exert full effects. A study of 3,000 cases of severe depression in the American Journal of Psychiatry found that less than 30 per cent had remission after taking SSRIs.
A nasal spray has been investigated, as it offers quicker relief because the drug gets to where it is needed in the brain without being processed through the body.
While most existing drugs act on the brain chemical serotonin, which is involved in mood regulation, esketamine acts on another chemical, glutamate.
Research has shown that problems with connections between nerve cells in the brain may lead to depression. One theory is that it is associated with a wasting away of nerve cells in brain regions that control mood and emotion, possibly as a result of stress.
Glutamate, released by nerve cells in the brain, is one chemical responsible for sending signals between nerve cells. However, too much glutamate is bad for the brain, leading to nerve cell loss, and has been linked to depression.
Esketamine works by blocking excess glutamate and this is thought ultimately to repair and restore nerve cells. Animal studies dating back to the Fifties have suggested drugs that act on glutamate may be effective for depression. But it was not until 2000 that the first small study in humans found similar effects.
One new study, reported in the Journal of Psychiatric Research, analysed data on 14 patients given esketamine.
Results showed four of the seven people using the spray responded to treatment after two hours and three went into remission.
None of the seven taking a placebo saw an improvement.
Around 1,150 patients are taking part in a study of the drug at hospitals across the U.S., Canada, South America and Europe. They will use the esketamine nasal spray twice a week; they'll be monitored for around five years.
Carmine Pariante, a professor of biological psychiatry at King's College London, said: ‘It is important to stress that only selected patients will use this drug — those with severe depression and who do not respond to currently available antidepressants.
‘Longer studies are needed to fully understand the risks of using this medication. Nevertheless, it is truly exciting that, after many years, we finally have an antidepressant that acts on a completely novel mechanism in the brain.'