Scientists have identified why common anti-depressants cause around a half of users to feel emotionally ‘blunted’.
Around 1 in 6 (17%) adults aged 16 years and over in Great Britain experienced some form of depression in summer 2021, with the rate higher than before the coronavirus pandemic when 1 in 10 adults experienced some form of depression, according to the Office for National Statistics (ONS). The NHS has reported that more than 8.3 million patients in England received an antidepressant drug in 2021/22. In addition, data from the NHS Business Services Authority highlighted there were an estimated 21.4 million antidepressant drugs items prescribed between July and September 2022.
Selective serotonin reuptake inhibitors (SSRIs), are a commonly used class of antidepressants. However, “one of the widely-reported side effects of SSRIs is ‘blunting’, where patients report feeling emotionally dull and no longer find things as pleasurable as they used to,” explained the authors of a new study published in Neuropsychopharmacology.
“Between 40-60% of patients taking SSRIs are believed to experience this side effect,” they pointed out.
Professor Barbara Sahakian, department of psychiatry, University of Cambridge, and senior author of the study, 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.”
'Hot' and 'Cold' Cognition
To explore this phenomenon, a team led by Cambridge University researchers, in collaboration with Copenhagen University, set out to investigate the chronic effect of escitalopram on measures of ‘cold’ cognition - including inhibition, cognitive flexibility, and memory - and ‘hot cognition’ - including decision-making and, particularly, reinforcement learning.
The double-blind placebo-controlled study - conducted at the University of Copenhagen between May 2020 and October 2021 - involved 66 healthy volunteers, aged between 18 and 45, recruited from a database at the Neurobiology Research Unit at the University of Copenhagen.
Participants were matched for age, sex, and intelligence quotient (IQ) and semi-randomised into two groups - one group (32 participants) received escitalopram 20 mg daily, and the other group (34 participants) received placebo, for at least 21 days.
Participants completed self-report questionnaires, which included an assessment of depressive symptoms, anxiety, impulsivity, compulsivity, and personality traits. These were completed at baseline, before medication administration, and a subset were repeated after at least 21 days at a cognitive visit – which assessed cognitive function including learning, inhibition, executive function, reinforcement behaviour, and decision-making. Finally, a subset were repeated again one week after the cognitive visit once the medication administration had ceased. At baseline, participants completed the CANTAB Reaction Time task (RTI) and Reynolds Intellectual Assessment Scales (RIAS) to assess IQ.
Reduced Reinforcement Sensitivity
"There were no significant group differences, after correction, between the placebo and escitalopram groups on any of the baseline questionnaires”, the authors said. In addition, there were no group differences for reaction time on the CANTAB RTI at baseline.
The researchers found "no significant group differences" when it came to ‘cold’ cognition – such as attention and memory. There were also no differences in most tests of ‘hot’ cognition – cognitive functions that involve emotions.
However, the "key novel finding", they said, was that there was "reduced reinforcement sensitivity" on two tasks for the escitalopram group compared with those on placebo. "Reinforcement learning is how we learn from feedback from our actions and environment," they explained.
To assess reinforcement sensitivity the researchers had used a 'probabilistic reversal tes'. In this task, a participant would typically be shown two stimuli, A and B. If they chose A, then four in five times they would receive a reward; if they chose B, they would only receive a reward one time in five. Volunteers would not be told this rule, but would have 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 authors highlighted 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 suggested, they said, that the drug affected their "sensitivity" to the rewards and their "ability to respond accordingly".
"Lower reinforcement sensitivity in response to chronic SSRI administration may reflect the ‘blunting’ effect often reported by patients with major depressive disorder treated with SSRIs," they hypothesised.
Prof Sahakian suggested that SSRI antidepressants' effect of taking away some enjoyment could be a consequence of making a person "less sensitive to rewards, which provide important feedback".
The authors highlighted the need for future studies to examine chronic administration of SSRIs beyond 21 days, and suggested that these should examine the chronic effects of SSRI administration on a similar extensive battery including 'cold', and 'hot' cognition, particularly reinforcement behaviour in patients with neuropsychiatric disorders.
"Our findings provide important evidence for the role of serotonin in reinforcement learning," impassioned Dr Christelle Langley, department of psychiatry, University of Cambridge, and joint first author.
Funding for the study was provided by the Lundbeck Foundation.
