Study explains emotional ‘dulling’ caused by common antidepressants

overview: SSRI antidepressants can reduce a user’s sensitivity to rewards, resulting in the emotional blunting experienced by many users. This finding provides new evidence for the role serotonin plays in reinforcement learning.

sauce: Cambridge University

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

More than 8.3 million people in the UK were on antidepressants in 2021/22, according to the NHS. A widely used class of antidepressants, especially in 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.”

One widely reported side effect of SSRIs is ‘slowness’, in which patients report feeling emotionally sluggish and not finding things as enjoyable as they used to. It is believed that 40-60% of patients taking SSRIs experience this side effect.

So far, most studies on SSRIs have only investigated short-term use, whereas in clinical use for depression, these drugs are taken chronically over long periods of time. A team led by researchers from the University of Cambridge, in collaboration with the University of Copenhagen, will recruit healthy volunteers to administer escitalopram, the best-tolerated SSRI known to be best tolerated, over several weeks and assess the effects. I tried to address this issue by The drug affected performance on a battery of cognitive tests.

A total of 66 volunteers participated in the study, 32 of whom received escitalopram and the remaining 34 received placebo. Volunteers took the drug or placebo for at least 21 days, completed a series of comprehensive self-report questionnaires, and underwent a battery of tests assessing cognitive functions including learning, inhibition, executive function, reinforcing behavior, and decision-making. .

Today, the results of the study neuropsychopharmacology.

The team found no significant differences between the groups when it came to “cold” cognitions such as attention and memory. Most tests of “hot” cognition (cognitive functions with emotion) showed no difference.

An important new finding, however, was a reduction in reinforcement sensitivity in two tasks in the escitalopram group compared to the placebo group. Reinforcement learning is a method of learning from behavioral and environmental feedback.

To assess the sensitivity of reinforcement, researchers used the ‘probabilistic reversal test’. In this task, the participant is typically presented with her two stimuli, A and B. If you choose A, you will receive a reward 4 times out of 5. If she chooses B, she will only receive rewards once out of five.

Volunteers are not taught this rule, they have to learn it themselves, and at some point in the experiment the probabilities switch and participants have to learn the new rule.

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

The findings may explain one difference the team found in the self-reported questionnaire, namely that volunteers taking escitalopram had more difficulty reaching orgasm during sex. there is. This is a side effect often reported by patients.

Professor Barbara Sahakian, lead author and Claire Hall Fellow, Department of Psychiatry, University of Cambridge, said:

“In a way, this may be part of what they do. It takes away some of the emotional pain that people who have experienced depression feel, but unfortunately it also seems to take away some of the fun.” Our research shows that this is due to decreased sensitivity to rewards that provide important feedback.”

Dr. Christelle Langley, a psychiatrist and co-lead author, adds: We continue this work in a study examining neuroimaging data to understand how escitalopram affects the brain during reward learning. “

Funding: This research was funded by the Lundbeck Foundation.

About this psychopharmacological research news

author: Craig Brierley
sauce: Cambridge University
contact: Craig Brierley – University of Cambridge
image: image is public domain

Original research: open access.
“Chronic escitalopram in healthy volunteers has specific effects on enhanced susceptibility: a double-blind, placebo-controlled, semi-randomized study.” by Barbara Sahakian et al. neuropsychopharmacology

See also

overview

Chronic escitalopram in healthy volunteers has specific effects on enhanced susceptibility: a double-blind, placebo-controlled, semi-randomized study.

Several studies of the cognitive effects of selective serotonin reuptake inhibitors (SSRIs) administered acutely or subchronically in healthy volunteers found altered learning and reinforcement outcomes.

In contrast, to our knowledge, there are no studies on the chronic effects of escitalopram on cognition in healthy volunteers. This is important in terms of clinical use in major depressive disorder (MDD) and obsessive-compulsive disorder (OCD).

As a result, we aimed to investigate the chronic effects of the SSRI, escitalopram, on ‘cold’ cognition (including inhibition, cognitive flexibility, and memory) and ‘hot cognition’ (including decision-making, particularly reinforcement learning). was measured.

The study, conducted at the University of Copenhagen from May 2020 to October 2021, tested 20 mg of escitalopram (n= 32) or placebo (n= 34), balanced for age, gender and intelligence quotient (IQ) for at least 21 days. Questionnaires, neuropsychological tests, and serum escitalopram measurements were performed.

Group differences on cognitive measures were analyzed using linear regression models and innovative hierarchical Bayesian modeling of a probabilistic reversal learning (PRL) task. A novel and significant finding was that escitalopram reduced reinforcement sensitivity compared to placebo in both the sequential model-based/model-free task and the PRL task. No other significant group differences were found regarding ‘cold’ or ‘hot’ cognition.

These findings implicate serotonin reuptake inhibition in reinforcement learning in healthy individuals. The decreased enhanced sensitivity in response to chronic SSRI administration may reflect the ‘blunting’ effect often reported by MDD patients treated with SSRIs.

Trial registration: NCT04239339.