The University of Cambridge scientists have discovered why selective serotonin reuptake inhibitors (SSRIs) cause emotional ‘blunting’.
In a new study, scientists have found out why common antidepressants, SSRIs, cause around half of users to feel emotionally ‘blunted’. Emotional ‘blunting’ is a widely-reported side effect of SSRIs causing patients to feel emotionally dull and no longer find pleasure in things they once did. Around 40-60% of patients taking SSRIs are believed to experience this side effect.
Antidepressants were prescribed to over 8.3 million patients in England in 2021/22. SSRIs are commonly used for persistent or severe depression cases. They target serotonin, a chemical that carried messages between nerve cells in the brain and has been dubbed the ‘pleasure chemical’.
The results of the study are published in Neuropsychopharmacology.
Researching the effect of SSRIs on emotions
The majority of studies on the effects of SSRIs have only been examined for their short-term use, but for clinical use in depression, these drugs are taken chronically over a long period. Researchers from the University of Cambridge worked with the University of Copenhagen to examine healthy volunteers and administered escitalopram, an SSRI that is known to be one of the best tolerated, over several weeks and assessed the impact the drug had on their performance on a suite of cognitive tests.
In total, 66 volunteers took part in the experiment; 32 were given the SSRI, and the other group were given a placebo. The volunteers took the drug or 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, reinforcement behaviour and decision making.
Emotional blunting is common
The scientists found no significant group differences in ‘cold’ cognition, such as attention and memory. There were no differences in most tests in terms of ‘hot’ cognition, which are functions that involve emotions.
However, the key novel finding was that there was reduced reinforcement sensitivity on two tasks for the escitalopram group compared to those on placebo. Reinforcement learning is how we learn from feedback from our actions and environment.
To assess reinforcement sensitivity, the researchers used a ‘probabilistic reversal test’. In this task, a participant would typically be shown two stimuli, A and B. If they chose A, then four out of five times, they would receive an award; if they chose B, they would only receive a reward one time out of five. The volunteers were not told this rule and had to learn it themselves, and at some point in the experiment, the probabilities would switch, and participants would need to learn the new rule.
The team found that participants taking escitalopram were less likely to use the positive and negative feedback to guide their learning of the task compared with participants on placebo. This suggests that the drug affected their sensitivity to the rewards and their ability to respond accordingly.
Furthermore, this finding may explain the one difference in the self-reported questionnaires, that volunteers taking the SSRIs had more trouble reaching orgasm when having sex, a side effect commonly reported by patients.
Professor Barbara Sahakian, senior author, from the Department of Psychiatry at the University of Cambridge and a Fellow at Clare Hall, said: “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. From our study, we can now see that this is because they become less sensitive to rewards, which provide important feedback.”
Dr Christelle Langley, the 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 this work up with a study examining neuroimaging data to understand how escitalopram affects the brain during reward learning.”