Why antidepressants cause emotional blunting

According to figures published last year, more than 8 million people in the UK or about 1 person in every eight, used antidepressants in 2022. While these drugs can be very helpful and even a lifeline for some users, many complain that they leave them feeling emotionally blunted: enjoying things seems to be harder than it used to be. Now we think we might be on the way to understanding why: Cambridge University‘s Christelle Langley gave healthy volunteers a course of the common antidepressant escitalopram and tested a range of cognitive functions. She thinks taking the drug made the users’ brains less sensitive to reward signals, making it harder for them to enjoy some activities…

Christelle - Serotonin is the main brain chemical that is affected by selective serotonin re-uptake inhibitors, which is one of the main kinds of antidepressants. And there's been a lot of work in the field examining how serotonin affects cognition, but it's mainly been done acutely, which is single dose or for short term seven day administration. But of course, as we know, patients take these drugs for months and often even years. So because of this we really need to understand the longer term effects. More

Chris - People also say it takes a few weeks before they begin to feel better after they start taking them. So that's important, presumably.

Christelle - Exactly. So typically we say that it takes at least three weeks for these drugs to start working. And this is exactly the time point at which we looked. So, we gave participants either placebo or, as you've mentioned, the SSRI escitalopram for at least 21 days. And the reason we chose escitalopram specifically is it's one of the best tolerated SSRIs. So that was really important to us. And of course, conducting studies in healthy people also allows us to establish what effects might be due to the drug without looking at what's sort of confounded by the disease process.

Chris - You're not muddling up the disease that's underlying this and their inability to enjoy things because of the disease, it's purely the effect the drug has.

Christelle - Exactly that. Yes.

Chris - And what did you find when you tested them and how did you test them?

Christelle - So we used a number of different tests assessing what we called 'cold cognition' and 'hot cognition'. So cold cognition is rational non-emotional cognition and it's things such as attention and memory. Whereas hot cognition is something that has either social or an emotional element. So interacting with friends, anything like that would be hot cognition. And we also specifically looked at reinforcement learning. And this is how we learn from our environment through either rewarding and positive or negative feedback

Chris - So I give you something and you give me something back in return and I think, 'oh, that's good'. And I learn from the fact that when I give you something, I've got something I wanted back. That would be positive reinforcement.

Christelle - Exactly, yes.

Chris - Right. Okay. And how did that work in this task then? Or what difference was there when you do all these things?

Christelle - So in this task, quite interestingly, we actually build in a certain amount of uncertainty. So if you choose the correct stimulus, four out of five times you're told yes you are correct. But actually one out of five times we misleadingly tell you that you are incorrect. And previous studies have shown that patients with depression are overly sensitive to this negative feedback and they incorrectly respond to the task. So they'll actually switch immediately after receiving negative feedback, even though they know that that should be the correct stimulus.

Chris - And what happened with these people who didn't have depression but were taking this antidepressant drug.

Christelle - So this was our key novel finding, was that participants on escitalopram had a lower reinforcement sensitivity and actually we saw it on two different tests of reinforcement learning. So it seems quite a robust finding. And essentially there were no other differences on any of the other hot or cold cognitive tests. And actually this null finding is quite encouraging because it suggests that they don't have, or that serotonin doesn't have, an adverse effect on, cognition generally but it seems to be that there's something quite specific in the way in which people process either negative or positive feedback

Chris - Putting this together, then. Essentially what you are demonstrating is this is how these drugs help people who are depressed. Because if a person is shielded from responding too much to the knocks of life, that stops them feeling so depressed or stops their disease or underlying condition accelerating. But at the same time, if you are too robust against encouragement, which is what also appears to be happening, then you don't enjoy things as much, which is what you found.

Christelle - Yes. So, patients with depression often report hypersensitivity to negative feedback or they have what we call negative attentional biases. So this would be, for example, when a healthy person is walking down the street, they'll focus on all the happy smiling faces around them, whereas someone with depression might focus on that single person that's walking down the street looking sad and upset. So of course dampening down the negative emotions or distress that depressed patients feel might be a therapeutic process and how these drugs are actually working. But because we can't selectively choose the negative emotions, we're unfortunately seems that they're taking away from some of the enjoyments as well. This doesn't necessarily mean that they're not effective, it's just we've now got a little bit more understanding about how these drugs may work. And this will in future allow us to choose better treatment options as well.

Chris - I was going to say, does this give us a framework to try to make either better drugs, because we can look for drugs that don't necessarily have this effect quite so much, or does it enable us to tailor therapy better so that we can try to get some of the positives but minimize this negative effect? Because at the end of the day, people don't want to walk around feeling numb. They want to feel better, but they don't want to feel emotionally numb.

Christelle - No, exactly. So I think the interesting thing is that we need to understand how these drugs work essentially. And this gives us some insight. As I say, the therapeutic process might be the dampening down, but actually this might not be necessary throughout the whole course of treatment. And actually initially, by being able to dampen down the emotions, you can get to a point where something like cognitive behavioral therapy or some of the psychological therapies may be more effective. So we know what we tend to do in CBT is we try and get people to think about things in a more positive light, but these often don't work in very severe patients before medication.