A new study explains the reasons behind the emotional ‘dulling’ that affects about half of people taking SSRIs, a common family of antidepressants. influences reinforcement learning. This is an important behavioral process that allows us to learn from our surroundings.
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 is called the “pleasure chemical.” Common SSRIs include citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil, Pexeva), fluoxetine (Prozac), and sertraline (Zoloft).
One widely reported side effect of SSRIs is ‘slowness’, with patients reporting feeling sluggish and unable to find 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 examined short-term use, but for clinical use in depression, these drugs are taken chronically over long periods of time.A team led by researchers from Cambridge University, University of Copenhagenattempted to address this by recruiting healthy volunteers and administering escitalopram.
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. .
The results of this study will be published today (January 23, 2023) in a journal. 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, Senior Author and Clare Hall Fellow, Department of Psychiatry, University of Cambridge, said: In a way, this may be part of how they work — they take away some of the emotional pain that people who have experienced depression feel, but unfortunately, they also It seems to take some of the fun out of it. ”
Dr. Christel Langley, a psychiatrist and co-lead author, adds: We continue this work with a study examining neuroimaging data to understand how escitalopram affects the brain during reward learning. ”
Reference: “Chronic Escitalopram in Healthy Volunteers Has Specific Effects on Reinforcement Sensitivity: A Double-Blind, Placebo-Controlled, Semi-Randomized Trial”, Langley, C, Armando, S, et al., 2023 1 23rd of the month, neuropsychopharmacology.
DOI: 10.1038/s41386-022-01523-x
This research was funded by the Lundbeck Foundation.
