New anti-depressants can act within days

A new class of fast-acting antidepressants that improve symptoms within days could soon be in development, according to a Canadian study.

Researchers compared the efficacy of direct serotonin receptor agonists with that of the SSRI citalopram in a rat model of depression. They found that the serotonin receptor agonists were as effective as the SSRI, but worked much more quickly.

Serotonin receptor agonists are compounds that mimic the effect of the neurotransmitter serotonin. Because they stimulate serotonergic neurons directly researchers believed that they should have a quicker onset of action than SSRIs, which work by increasing the amount of serotonin available outside the cell.

The researchers tested this theory with two compounds that target serotonin type-4 receptors, RS673333 and prucalopride, in a behavioural model of depression in rats. They subjected 40 rats to chronic mild stress for two weeks to induce depression. A third of the rats were treated with RS67333, a third with citalopram, and a third with a placebo.

Rats given the serotonin agonist recovered their usual rate of sucrose consumption after three days, while those given the SSRI took 24 days of continuous administration.

The researchers also found that key markers of antidepressant action that are usually seen after two to three weeks in SSRI treatment, such as the creation of new neurons in the hippocampus, were visible within three days of treatment with the serotonin agonists.

Lead researcher Dr Guillaume Lucas from the department of psychiatry at McGill University, Montreal, said: 'Based on the behavioural and in vitro data that we have on serotonin agonists, we propose that these could be a new class of fast-acting antidepressants.'

'We hope that our finding will lead to clinical trials of serotonin receptor agonists for depression,' he said.

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