New insights into how antidepressants work.


fMRI scan.

It is well established that antidepressants take at least 2 weeks to shift a depressed mood. A new study from researchers at Oxford, reveals that the drug is working behind the scenes, much earlier than this.

People with depression are known to show an exaggerated response to pictures of human faces that are expressing fear. The response can be observed using functional MRI brain scanning. The part of the brain which lights up is their own 'fear processor', the amygdala. The usual interpretation is that the depressed patient's fear system is unduly sensitive to anything from the outside world which signifies fear. And human faces elicit the most robust response.

Previous work had shown that standard SSRI antidepressants can dampen down the hyperactive amygdala, and return it's function to normal. What was unknown was whether the effect on the amygdala or the effect on mood came first.

The Oxford researchers have now shown that SSRI antidepressants dampen down the amygdala at least 1 week before the patient experiences a shift in their mood. They compared 3 groups of people: depressed patients who had been randomised to receive escitalopram (10mg); depressed patients who had been randomised to placebo; and a group of healthy controls. A week after being randomised to active drug or placebo, the depressed patients were given an fMRI scan.

The main finding was that the patients who had been taking escitalopram for a week had normal amygdala responses to pictures of fearful human faces. In contrast, the patients on placebo showed the characteristic hyperactive response in the amygdala on the right hand-side of their brains (see scan above). Notably, 1 week was too early for any antidepressant effect – Treated and untreated patients were equally depressed at this stage.

This is an important finding, which shows that SSRI antidepressants affect how the brain processes emotional information before the patient feels an improvement in their mood.

Further studies are planned. One key goal will be to assess if the degree of amygdala dampening at 1 week can distinguish between patients who ultimately get better from those who will remain depressed. The technology might even be used in selecting the 'best' type of antidepressant drug for a particular patient, rather than having to adopt a 'wait and see' approach.

The full paper can be read here