How Drugs Work: Anti-depressants

This post was requested by the very lovely Bex, who is some kind of crafting Goddess. This post isn’t actually anything to do with crafting though, which is lucky because when I craft I usually tie things in knots, and glue bits of myself to other bits of myself, and it’s all a bit messy and less than brilliant. But as I said, crafting isn’t the point of this post, Bex has asked me to explain how anti-depressants work, and this post is specifically about a class of anti-depressants called selective serotonin re-uptake inhibitors (SSRIs).

Before I go on, I want to make it very very clear right now that this isn’t intended to advise you as to whether antidepressants are something that you need or will help you. Depression is an incredibly difficult and challenging thing to understand, and not everyone experiences it in the same way. If you think you may be suffering from depression, I would encourage you to contact your GP, or someone professionally qualified to help you. This is going to be about HOW certain anti-depressants are likely to work, but it won’t tell you if they’re right for you, that’s a decision for you and your GP, or for you to discuss with a counsellor.

So. Your brain. Your brain is so complex, it’s actually quite breathtaking. Messages are zipping and zapping about all over the place. Nerve cells pass messages along their lengths in the form of negative charges called action potentials. These super little impulses shoot along nerve cells, like Road Runner on speed, until they reach the end of the line and come to a sudden halt. A huge canyon looms ahead of them, a synapse, with another nerve cell on the other side. The message has to get across the synaptic gap, to get to where it needs to go, but the action potential just can’t make the jump. It would be stuck, shouting into a void, were it not for the existence of some handy neurotransmitters.

Neurotransmitters can cross the canyon of the synapse. They have specially designed clever gear that allows them to be released, with a leap, from the surface of the pre-synaptic nerve cell, and fly across the chasm, where they are caught by receptors on the surface of the post-synaptic nerve cell. Neurotransmitters are terribly brave, casting themselves across the gap without caution, trusting that a receptor will be there to greet them, and take their message forward.

Once they’ve successfully traversed the gap, and passed the message to the receptor on the new cell, neurotransmitters have got to get back to their original nerve cell. Suddenly, they’re frightened. When there was an urgent message to share, they leapt bravely without thinking about it, but on the way back they suddenly realise how far they have to go, and panic. Instead of leaping back, they are released by the receptors, and collected by a kindly monoamine transporter, providing a shuttle service back to their original cell. This process is known as reuptake. If monoamine transporters didn’t come along to do this job, the neurotransmitters would hang around at the edge of the gap, clinging to the receptors, and yelling their message repeatedly.

Serotonin is one of the intrepid synapse-crossing neurotransmitters, and what SSRIs do is slow down the reuptake of serotonin into the original nerve cell, thus leaving it in the synaptic gap longer. This means that serotonin keeps on clinging to the receptors, and keeps shouting out its message to the receptor cell. SSRIs may also work in a similar way to strand dopamine and norepinephrine in the synpatic gap. The implication is, of course, that low levels of serotonin, dopamine and epinephrine are linked to depression.

So, that is the mechanism of action for SSRIs; however with depression nothing is simple. Not all depression is necessarily linked to or caused by low levels of serotonin, dopamine or norepinephrine, so often taking SSRI anti-depressants is a trial and error experience, it won’t automatically work for everyone.

On top of this, there is another level of confusion, as there so often is in biochemistry. There is another drug that can have anti-depressant effects, tianeptine, which is actually a selective serotonin reuptake enhancer. It acts in the complete opposite way to SSRIs. This clearly doesn’t make sense, unless the links between serotonin, dopamine, norepinephrine and mood are a lot more complicated than we thought. This means that although we know what SSRIs actually do from a molecular perspective, we’re still not entirely sure how that relates to depression.

Ultimately, there’s no way of knowing, at the moment, whether SSRIs are likely to work for you. And on top of all THAT, there can be adverse side effects to SSRIs, much like with any drug. Again, and I hate to repeat myself, but this is super important to me, this is a thing that you should discuss with your GP if you think you’re suffering from depression, and want to talk about getting help.  The conversation about risks and side effects and the decision to try SSRIs is something for you and your Doctor, not something that a nerdy science blogger can solve. A nerdy science blogger can just sit here and tell you that whether or not they work for everyone, the fact that we as human beings can actually design a drug that can work somewhere as complicated as your brain, on something as misunderstood, complex and awful as depression, is pretty damn amazing.

As part of this post I would also like to say that I wholeheartedly support the Time for Change campaign, which is working to destigmatise mental heath issues and end discrimination against people who suffer with them. 


8 thoughts on “How Drugs Work: Anti-depressants

  1. Thanks for a very interesting and accessible account of antidepressant drug action. I wonder if you have thought about the paradox whereby the drugs affect brain monoamine levels quite quickly but have clinical effects only after several weeks. This suggests that the therapeutic effect of the drug depends on another process. People in the field are talking about changes in neuronal numbers, neuronal connections and growth factors.

    Also I don’t think it necessarily follows that because a drug affects serotonin levels then the disorder is due to disturbances in serotonin. People have looked for changes in serotonin in depression and the results have not been convincing.

    • Thanks so much for your comment! I was aware of the strange monoamine paradox but I didn’t understand the phenomenon enough to feel happy writing about it. I’m going to do some more research though and come back to this with a follow-up post!

      I also completely agree that it’s impossible to assume that depression is linked to low serotonin levels; for one thing there little evidence to support that, as you say, but for another your brain and your moods and emotions are so ridiculously complex that to presume that one nuerotransmitter is responsible for such a poorly understood condition as depression would be difficult to believe. You’re quite right though, and I hope I got across that I genuinely don’t think that serotonin is responsible for depression, I think that if SSRIs work for you then that’s brilliant, and this is how they work from a molecular perspective, but that doesn’t look at how they work on a higher biological level.

      K x

  2. Oh wow! this is amazing! thank you so much. Its so brilliant to be able to read it in words that make sense to me! I also totally agree on finding the write meds for you – it took 8 years to find the right ones for me. I am also a BIG believer in talking! talk talk talk – it helps!

    Thank you!

    • Thanks Bex, you’re very welcome, I’m so glad it was helpful to you! As someone who has had quite a lot of counselling and cognitive behavioural therapy for anxiety issues, I definitely agree with the talk, talk, talk.

      K x

  3. Pingback: How Drugs Work: Anti-depressants | Science Communication Blog Network

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