Common antidepressants may blunt both pain and enjoyment

Feeling flat or emotionally unavailable can be a common side-effect of serotonin reuptake inhibitors (SSRIs), a widely used class of anti-depressants. About 40 to 60 percent of patients taking SSRI’s are believed to experience limited enjoyment or feel emotionally dull.

A small study published January 22 in the journal Neuropsychopharmacology is shedding light on why this “emotional blunting,” or the dulling of both good and bad emotions, may happen. The study finds that the drugs affect reinforcement learning, which allows us to learn from our environment and actions.

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“Emotional blunting is a common side effect of SSRI antidepressants. In a way, this may be in part how they work—they take away some of the emotional pain that people who experience depression feel, but, unfortunately, it seems that they also take away some of the enjoyment,” said Professor Barbara Sahakian, a co-author and professor of psychology the University of Cambridge, in a statement. “From our study, we can now see that this is because they become less sensitive to rewards, which provide important feedback.”

SSRIs target serotonin, a chemical in the brain called the “pleasure chemical” or the “happiness molecule” that carries messages between nerve cells. According to the National Health Service (NHS), more than 8.3 million patients in England received an antidepressant during 2021 and 2022. In the United States, prescriptions for anti-anxiety and antidepressants increased by an estimated 21 percent following the COVID-19 pandemic.

A team led by researchers at the University of Cambridge and the University of Copenhagen looked into the long term clinical use of SSRIs. They recruited 66 healthy volunteers and gave 32 of them an SSRI called escitalopram and the other 34 took a placebo. According to the team, this drug is known to be one of the best-tolerated antidepressants available on the market and the study participants took them over 21 days.

The participants completed self-reported questionnaires and were given a series of tests that assessed learning, inhibition, executive function, reinforcement behavior, and decision-making.

In terms of attention and memory (also called ‘cold’ cognition), there were no significant differences. There also weren’t any differences in ‘hot’ cognition, or the cognitive functions that involve emotions.

The key novel finding of the tests was a reduced reinforcement sensitivity on two tasks for the group taking escitalopram compared to those taking the placebo.

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The team used a probabilistic reversal test, where a participant was shown two stimuli (A and B). If they chose A, they would receive a reward four out of five times. If they chose B, they would only get a reward one time out of five. The participants weren’t told this rule, but would have to figure it out themselves. At some point during the test, the probabilities would switch, forcing participants to learn a new rule.

Compared with those taking the placebo, the participants taking escitalopram were less likely to use both the positive and negative feedback to guide their learning of the task. The participants on the antidepressants were 23 percent less sensitive to this stimuli switch, which suggests that escitalopram affected sensitivity to the rewards and the individual’s ability to respond accordingly.

This could also explain one big difference the team found in the self-reported questionnaires: volunteers taking escitalopram had more difficulty reaching orgasm when having sex, a widely-reported side effect of the medication.

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