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Common Antidepressants Cause Emotional "Dumbing" - Scientists Have Finally Figured Out Why

Emotionally dulled indifferent pills concept

A new study explains the reason behind the emotional “bluntness” that affects about half of people who take SSRIs, a family of common antidepressant medications. Research shows that drugs impact reinforcement learning, a crucial behavioral process that allows us to learn from our surroundings.

Scientists have discovered why common antidepressants make about half of users feel emotionally “dull”. In a study published today, they show that drugs affect reinforcement learning, an important behavioral process that allows us to learn from our environment.

According to the NHS, over 8.3 million patients in England were prescribed an antidepressant drug in 2021/22. A widely used class of antidepressants, particularly for persistent or severe cases, are selective serotonin reuptake inhibitors (SSRIs). These drugs target serotonin, a chemical that transmits 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 ‘dullness’, where patients report feeling emotionally numb and no longer find things as pleasurable as they once did. It is believed that between 40-60% of patients taking SSRIs experience this side effect.

To date, most studies of SSRIs have only examined their short-term use, but for clinical use in depression, these drugs are taken chronically, over a long period of time. A team led by researchers at 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 one of the best tolerated, for several weeks and assessing the impact of the drug. had on their performance on a set of cognitive tests.

In total, 66 volunteers participated in the experiment, 32 of whom received escitalopram and the other 34 received placebo. Volunteers took either the drug or the placebo for at least 21 days and completed a comprehensive set of self-report questionnaires and were given a series of tests to assess cognitive functions, including learning, inhibition, executive function, reinforcing behavior and decision making.

Study results were published today (January 23, 2023) in the journal neuropsychopharmacology.

The team found no significant differences between the groups when it came to “cold” cognition – such as attention and memory. There were no differences on most tests of ‘warm’ cognition – cognitive functions that involve our emotions.

However, the main new finding was that there was reduced sensitivity to reinforcement on two tasks for the escitalopram group compared with the placebo group. Reinforcement learning is how we learn from feedback from our actions and the environment.

To assess the sensitivity of the reinforcement, the researchers used a ‘probabilistic reversal test’. In this task, a participant would normally receive two stimuli, A and B. If he chose A, then four times out of five, he would receive a reward; if they chose B, they would receive a reward only once in five. The volunteers would not learn this rule, but would have to learn it themselves, and at some point in the experiment, the odds would change and the 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 their task learning compared to placebo participants. This suggests that the drug affected their sensitivity to rewards and their ability to respond accordingly.

The finding may also explain the only difference the team found in the self-reported questionnaires, that volunteers taking escitalopram had more difficulty reaching orgasm during sex, a side effect often reported by patients.

Professor Barbara Sahakian, senior author at the Department of Psychiatry at the University of Cambridge and a Clare Hall Fellow, said: “Emotional blunting is a common side effect of SSRI antidepressants. In a way, that may be part of how they work – they take some of the emotional pain that people suffering from depression feel, but unfortunately, it seems they also take some of the pleasure. From our study, we can now see that this is because they become less sensitive to rewards, which provide important feedback.”

Dr. Christelle Langley, joint first author also from the Department of Psychiatry, added: “Our findings provide important evidence for the role of serotonin in reinforcement learning. We are following up this work with a study examining neuroimaging data to understand how escitalopram affects the brain during reward learning.”

Reference: “Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a semi-randomized double-blind, placebo-controlled study” by Langley, C, Armand, S, et al., January 23, 2023 , neuropsychopharmacology.
DOI: 10.1038/s41386-022-01523-x

The research was funded by the Lundbeck Foundation.