Scientists have discovered that common anti-depressants cause nearly half of users to feel emotionally ‘dull’. In a study published today, they show that the drugs affect reinforcement learning, an important behavioral process that allows us to learn from our environment.
According to the NHS, more than 8.3 million patients in England will be prescribed antidepressant medication in 2021/22. One widely used class of antidepressants, especially for persistent or severe cases, is the selective serotonin reuptake inhibitors (SSRIs). These drugs target serotonin, a chemical that carries messages between nerve cells in the brain and has been dubbed the ‘pleasure chemical’. Common SSRIs include citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil, Pexeva), fluoxetine (Prozac), and sertraline (Zoloft).
One of the widely reported side-effects of SSRIs is ‘blunting’, where patients feel emotionally dull and no longer find things as enjoyable as they used to be. This side effect is thought to be experienced by between 40-60% of patients taking SSRIs.
To date, most studies of SSRIs have only examined their short-term use, but, for clinical use in depression, these drugs are taken for longer periods of time. A team led by researchers from the University of Cambridge in collaboration with the University of Copenhagen sought to address this by recruiting healthy volunteers and administering escitalopram, an SSRI known to be best tolerated, for several weeks and assessing the effect. Is. The drug had an effect on their performance on a suite of cognitive tests.
In total, 66 volunteers took part in the experiment, 32 of whom were given escitalopram while the other 34 were given a placebo. Volunteers took either the drug or a placebo for at least 21 days and completed a comprehensive set of self-report questionnaires and a series of tests to assess cognitive functions including learning, inhibition, executive function, reinforcement behavior and decision making Went.
The study results are published today (January 23, 2023) in the journal neuropsychopharmacology,
The team found no significant group differences when it came to ‘cold’ cognitions – such as attention and memory. There was no difference in most tests of ‘hot’ cognition – cognitive tasks that involve our emotions.
However, the major novel finding was that reinforcement sensitivity on the two tasks was lower for the escitalopram group compared to placebo. Reinforcement learning is how we learn to respond to our actions and environment.
To assess reinforcement sensitivity, the researchers used a ‘probability reversal test’. In this task, a participant is typically shown two stimuli, A and B. If they choose A, four times out of five, they will get a reward; If they choose B, they will get the prize only once out of five. The volunteers would not be told this rule, but would have to learn it on their own, and at some point in the experiment, the probabilities would change and participants would need to learn the new rule.
The team found that participants taking escitalopram were less likely to use positive and negative feedback to guide learning about the task than participants on placebo. This suggests that the drug affected their sensitivity to rewards and their ability to respond accordingly.
The finding may also explain a difference the team found in self-reported questionnaires, that volunteers taking escitalopram had more trouble reaching climax when having sex, a side effect often reported by patients. .
Professor Barbara Sahakian, senior author, Department of Psychiatry at the University of Cambridge and a Fellow at Clare Hall, said: “Emotional blunting is a common side effect of SSRI antidepressants. In a way, this may be partly how they work. – They take away some of the emotional pain that people with depression experience, but, unfortunately, they also seem to take away some of the pleasure. From our study, we can now see that this is because they are more likely to experience the rewards. become less sensitive to stimuli that provide important feedback.”
Dr Christel Langley, joint first author from the Department of Psychiatry, said: “Our findings provide important evidence for a role for serotonin in reinforcement learning. We are following this work with a study examining neuroimaging data to establish whether understand how escitalopram affects the brain during reward learning.
Reference: “Chronic escitalopram has specific effects on reinforcement sensitivity in healthy volunteers: a double-blind, placebo-controlled quasi-randomized study” by Langley, C, Armand, S, et al., 23 Jan 2023. neuropsychopharmacology,
The research was funded by the Lundbeck Foundation.