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Emotional “Blunting” From Common Antidepressants Explained

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A new study has discovered the possible origins of emotional “blunting”, experienced by as many as one in two users taking common antidepressants. The study is published in Neuropsychopharmacology.

A common side effect of SSRIs

Around 13% of US adults reported having used antidepressant medication in the previous 30 days during the period 2015–2018, according to a survey from the US Centers for Disease Control and prevention. One of the most widely used classes of antidepressants is a group called selective serotonin reuptake inhibitors (SSRIs). These drugs work by increasing the amount of serotonin – the so-called “feel-good hormone” – within the brain by preventing it from being reabsorbed.

Despite the widespread use of SSRIs, one of the most widely reported side effects is the feeling of emotions becoming dulled or “blunted”, experienced by ~40–60% of patients. These users describe finding less enjoyment or pleasure in things than they did previously.

While SSRIs are most effective when used long-term for conditions such as depression, most previous studies of these drugs have researched their short-term use. Now, researchers from the University of Cambridge and the University of Copenhagen have reported the results from their study which aimed to investigate the effect of the common SSRI escitalopram on the cognitive performance of healthy volunteers given the drug over several weeks.

Impacts on reinforcement learning

The researchers recruited 66 healthy volunteers to participate in a double-blind, placebo-controlled semi-randomized study. Over a 21-day period, 32 participants were given escitalopram while the other 34 received a placebo. Participants completed a variety of self-reported questionnaires to measure a range of cognitive functions such as learning, executive function, decision-making and reinforcement behavior.

At the end of the study, the researchers found no significant differences in functions like attention and memory, and there were also no significant differences in most emotional functions.

However, the crucial finding came when the team discovered that those in the escitalopram group had a reduced sensitivity to reinforcement learning – how we learn from our actions and the environment – relative to the placebo group.

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To measure this in more detail, the researchers put together a series of tasks called a “probabilistic reversal test” designed to assess their reinforcement sensitivity. Participants were shown two stimuli and asked to choose either stimulus A or stimulus B. Unknown to the participants, picking A would give them a reward four out of five times, whereas picking B would only give a reward one time out of five. Participants would eventually learn this rule, but the odds for A and B would switch during the experiment, requiring them to work out the new rule.

The results of this test showed that the escitalopram group had a reduced sensitivity to the rewards and a reduced ability to use positive and negative feedback to respond to the new rule. The researchers suggest that this also correlates with results from the self-reported questionnaires, in which participants taking escitalopram experienced difficulty reaching orgasm when having sex, another common side effect reported by patients taking SSRIs.

Can brain imaging reveal more?

“Emotional blunting is a common side effect of SSRI antidepressants,” explained Professor Barbara Sahakian, senior author of the study. “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. From our study, we can now see that this is because they become less sensitive to rewards, which provide important feedback.”

The authors also state that they plan to continue investigating these findings using neuroimaging studies to understand more about how escitalopram could be influencing the brain’s reward learning.

Reference: Langley C, Armand S, Luo Q, et al. Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomized study. Neuropsychopharmacol. 2023:1-7. doi: 10.1038/s41386-022-01523-x

This article is a rework of a press release issued by the University of Cambridge. Material has been edited for length and content.