How do antidepressants work?

What do antidepressants do in the brain?
09 April 2019


A bottle of tablets



How do antidepressants work?


What's going on in the brain when you take antidepressants? Chris Smith asked the University of Edinburgh's Stephen Lawrie...

Stephen - So I’ll try and keep it brief it's quite a complex question. The thing we know for absolute sure that antidepressants do quite quickly, is fundamental to how they work, is they increase the amount of chemicals that are the way that brain cells communicate with each other. So these chemicals like serotonin, adrenaline, noradrenaline, the ways that one nerve cell transfers its electric message to the next nerve cell down the line sort of thing. We don't know for sure whether that's enough, whether there are knock on effects as a result of that that are required for the antidepressant effect and the sorts of things that people think are probably involved. So quite quickly if you can show the effects of an antidepressant in people in terms of being less liable to process negative information or to process information that is neutral in a negative fashion and around about the same time you can also show that certain connections between different parts of the brain are enhanced. So a lot of depression is accompanied by what's called reduced connectivity between different parts of the brain that you can image with various imaging techniques

Chris - And they boot, they sort of pep that back more what we would regard as normal?

Stephen - They boost it, basically, yeah. And I think the best way of thinking about that, getting a handle on it is that a lot of people with depression are struck by brooding and very commonly worrying, or obsessive, kind of, negative thoughts and you can see that in a scanner with increased frontal-frontal conductivity your activation patterns and less long range frontal lobe to the rest of the brain, like connectivity. Antidepressants and indeed ECT interestingly enough.

Chris - That's an electric shock. That's the electric shock treatment? Electroconvulsive Therapy.

Stephen - That is probably the most effective antidepressant and what you would have if you were very severely depressed. They both seem to work at least in part it seems by reducing that frontal-frontal connectivity and increasing more long range connectivity in the brain.

Chris - And just in 30 seconds why is it that if you do experiments on people you can see the effect of drug molecules, of antidepressant drug molecules in the brain within days. Yet it takes say three or four weeks before people begin to feel better?

Stephen - Well that's partly a myth. Antidepressants have very quick effects and that you can see clinical benefits in patients within a few days. Very often patients are the last to notice and that's why they commonly are said to take two, three, four weeks. They actually have quite quick effects; within seven to 10 days usually.


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