Common Antidepressants Cause Emotional “Blunting” – Scientists Finally Figured Out Why

Emotionally blurred neutral pill concept

A new study explains the reason behind the emotional “blunting” that affects about half of people taking SSRIs, a common family of antidepressants. Research shows that drugs affect reinforcement learning, a critical behavioral process that enables us to learn from our surroundings.

Scientists have discovered why almost half of regular anti-depressant users feel emotionally ‘dull’. In a study published today, they show that the drug affects 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 took an antidepressant in 2021/22. A commonly used class of antidepressants, especially in persistent or severe cases, are the selective serotonin reuptake inhibitors (SSRIs). These drugs target serotonin, a chemical that carries messages between nerve cells in the brain and is known as the ‘happy chemical’. Common SSRIs include Citalopram (Celexa), Escitalopram (Lexapro), Paroxetine (Paxil, Pexeva), Fluoxetine (Prozac), and Sertraline (Zoloft).

One of the most commonly reported side effects of SSRIs is ‘blunting’, where patients report feeling emotionally drained and not finding things as pleasurable as they used to. It is believed that between 40-60% of patients taking SSRIs experience these side effects.

To date, most studies on 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 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 one of the best tolerated, over several weeks and assessing the effect. The drugs were based on their performance on a set of cognitive tests.

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

The results of the study are published today (January 23, 2023) in the journal Neuropsychopharmacology.

There were no significant group differences for the group regarding ‘cold’ cognitions such as attention and memory. There was no difference in many tests of ‘warm’ cognition – cognitive tasks involving our emotions.

However, the main new finding was that reinforcement sensitivity was reduced on two tasks for the escitalopram group compared with placebo. Reinforcement learning is how we learn from our actions and feedback from the 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 chose A, four out of five times, they would receive a prize; If they chose B, they would receive a reward only one out of five times. The volunteers will not be told this rule, but will have to learn it themselves, and at some point in the experiment, the probabilities will shift and the participants will need to learn the new rule.

The team found that participants receiving escitalopram were less likely to use positive and negative feedback to guide their learning about the task compared to participants on placebo. This suggests that the drug affected their sensitivity to rewards and thus their ability to respond.

The finding may also explain one of the differences the group found in self-reported questionnaires, with volunteers taking escitalopram having trouble getting arousal during sex, a frequent side effect reported by patients.

Professor Barbara Sahakian, senior author and Clare Hall Fellow, Department of Psychiatry, University of Cambridge, said: “Emotional blunting is a common side effect of SSRI antidepressants. In a way, this may be part of how they work—they take away the emotional pain felt by people experiencing depression, but, unfortunately, they also seem to take away some of the joy. From our study, we can now see that this is because they are less sensitive to rewards that provide important feedback.

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

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

The research was funded by the Lundbeck Foundation.



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