- Researchers investigated the effects of the selective serotonin reuptake inhibitor escitalopram (Lexapro) on the mental processes of healthy volunteers taking the drug over several weeks.
- They found that escitalopram negatively impacted reinforcement learning, but did not influence other measures of cognition, including attention, memory, and emotional processing.
- The researchers believe that the reduced reinforcement sensitivity caused by escitalopram may reflect the emotional blunting effect frequently reported by people taking selective serotonin reuptake inhibitors (SSRIs), but further work is necessary to understand the underlying mechanism.
Serotonin is a molecule in the brain that carries messages between brain cells and regulates mood, which is why it is also known as the “feel-good chemical.”
Since the 1960s, experts have widely believed that an imbalance of serotonin and other chemicals in the brain is the reason behind depression, although there is an ongoing debate about this theory.
People with depression frequently receive prescriptions for selective serotonin reuptake inhibitors (SSRIs). These drugs block the breakdown and reabsorption of serotonin into brain cells, thus increasing serotonin levels in the brain and helping to relieve depression.
SSRIs and ’emotional blunting’
An unwanted side effect of SSRIs, especially — though not only — in people taking them for a long time, is a diminished emotional response to both unpleasant and pleasurable events, referred to as “emotional blunting.”
Research has shown that about 40–60% of people taking SSRIs to manage depression experience some degree of emotional blunting.
The exact mechanism by which SSRIs may provoke emotional blunting is not known. To uncover this mechanism, researchers need to understand the effects of SSRIs on cognition, or mental processes.
Previous research has examined the effects of short-term use of SSRIs on cognition, but no studies have examined the cognitive effects of SSRIs taken over a longer period of time.
Now, a team of researchers at the University of Cambridge and the University of Copenhagen conducted a study among healthy volunteers to investigate the cognitive effects of the SSRI escitalopram — sold under the trade name Lexapro — over several weeks.
The results of this study appear in the journal Neuropsychopharmacology.
Prof. Philip Cowen, professor of psychopharmacology at the University of Oxford Department of Psychiatry, in the United Kingdom, who was not involved in the study, told Medical News Today:
“This was a well-conducted study carried out by a distinguished group of investigators. Learning more about the neuropsychological effects of widely used drugs, like SSRIs, is an important goal. The authors carried out a wide range of neuropsychological [tests] that included, reward learning, emotional processing, moral reasoning and tests of learning and memory. The sample size [66 participants] was good.”
Since cognitive impairment is frequently observed in people with depression, it may be challenging to distinguish the cognitive effects of depression from those of SSRIs.
This study was performed with healthy volunteers, “so the effect of the drug is not confounded by any history of depression,” Dr. Leigh Gibson, reader in biopsychology at the University of Roehampton, who was not involved in the study, told MNT.
The researchers split 66 healthy volunteers into two groups, which were matched for age, sex, and intelligence quotient. The volunteers took either 20 milligrams of escitalopram ( 32 participants) or a placebo ( 34 participants), for at least 21 days.
Neither the volunteers nor the medical personnel knew which treatment each participant was receiving.
The volunteers then completed a comprehensive set of self-report questionnaires and neuropsychological tests to assess a wide range of cognitive functions.
Reinforcement learning is the process in which a person or animal utilizes their previous experience to improve the outcomes of future choices.
The researchers found that escitalopram reduced reinforcement sensitivity compared to the placebo on two separate tasks. Participants taking escitalopram were less responsive to both positive and negative feedback when learning of a task compared with participants on the placebo.
“There was an impact of escitalopram to lower reinforcement learning. Clinically this might affect how hard people work for positive goals and what they experience when they achieve them,” Prof. Cowen told MNT.
The researchers noted that all other cognitive measures they tested in this study, including attention, memory, and emotional processing, were not influenced by 3 weeks of escitalopram treatment.
The researchers suggest that the observed reduction in reinforcement sensitivity may be linked to the emotional blunting that some patients experience when taking SSRIs.
Dr. Christelle Langley, joint first author of the study and research associate at the University of Cambridge Department of Psychiatry, in the U.K., told MNT that “[t]he study has clinical implications for understanding that the ‘blunting’ effect reported by many patients may not simply be due to [depression], but may be due to the medication they are taking.”
“This is not to say that patients should not take their medication, as many antidepressants are life-saving, but it does highlight that more work is required to understand the mechanisms by which the drugs work,” she pointed out.
In their comments to MNT, Dr. Gibson and Prof. Donatella Marazziti, professor of psychiatry at the University of Pisa, agreed that this study adds to existing research supporting the emotional blunting effects of SSRIs.
However, Prof. Cowen questioned the association between reduced reinforcement sensitivity and emotional blunting, noting:
“Most patients describe ’emotional blunting’ [as] the ability to experience positive and negative emotions. It isn’t obvious how reinforcement learning relates to this experience. Also, the test of emotional processing carried out in the study did not show evidence of emotional blunting, neither was emotional blunting apparent in the subjective rating scales.”
Dr. Langley told MNT that since the study was performed among healthy volunteers, their “interpretation is speculative of what may be seen in a group with depression.”
“Further work is required to examine this effect in [major depressive disorder] patients,” she added.
Prof. Marazziti pointed out that SSRIs typically take 4–8 weeks to block the serotonin transporter and elicit a significant antidepressant effect.
“[O]ne might argue that the reported reduced sensitivity might be fortuitous or disappear or worsen maybe in the long-term,” she said.
Prof. Marazziti added that the sample size did not allow for the distinction of sex-related differences, and that the effect of the highly specific escitalopram cannot be extrapolated to other SSRIs with a broader spectrum of activity.
Prof. Guy Goodwin, emeritus professor of psychiatry at the University of Oxford Department of Psychiatry, commented that: “Unfortunately they do not actually measure emotional blunting, which is a subjective experience […] Since it would have been perfectly possible to ask their participants directly about their emotional blunting, this is a missed opportunity.”
Dr. Gibson also observed that “the number of questionnaires (17) and cognitive tests (12) that participants had to complete at one sitting […] would be quite fatiguing, and although the same for both groups, one wonders whether any drug effect might interact with performance of increasingly fatigued participants?”
Further work is necessary to understand the mechanisms underlying SSRI-related emotional blunting. In order to better understand how escitalopram impacts the brain during reward learning, Dr. Langley and coworkers are planning a study that examines neuroimaging data.
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