Reinforcement sensitivity is an important behavioural process that allows us to learn from our environment through either positive/rewarding or negative feedback. When we get together with friends or go for a run, chemicals in our brains send us signals that in turn make us feel good about what we’re doing. We know that depressed patients commonly report “emotional blunting” after longer use of antidepressants, in which they experience a dulling of both positive and negative emotions. But it can be difficult to tell if these symptoms are due to the depression itself or the drug treatment.
Using healthy volunteers, our new study is the first to show that chronic use of antidepressants does decrease sensitivity to positive reward as well as negative feedback, and this finding may explain the dulling feeling experienced by some depressed patients.
The WHO estimates that about 350 million adults, or 5% of the global population, have depression. It is the leading cause for disability worldwide.
Since patients with depression may be prescribed selective serotonin reuptake inhibitor (SSRI) drugs indefinitely, it is important to understand their long-term effects. Our recent article, published in Neuropsychopharmacology, is the first to examine the cognitive, behavioural and emotional effects of long-term SSRIs in healthy people. Without studies on healthy volunteers, it’s difficult to pinpoint the cause of patients’ symptoms. For example, non-medicated patients with depression frequently have cognitive impairments, including heightened sensitivity to negative feedback, which may suggest depression not antidepressants as the cause.
Escitalopram is an effective treatment for many people with moderate-to-severe depression and is one of the best-tolerated SSRIs. Our study tested 66 healthy volunteers who were either given a placebo or the SSRI drug, escitalopram, for at least 21 days.
We found escitalopram reduced participants’ reinforcement sensitivity compared to those on placebo.
These findings also showed that the brain chemical serotonin, known as the “happy chemical” is involved in reinforcement learning in healthy people. The lower reinforcement sensitivity noted in the escitalopram group may be similar to the blunting effect (feeling emotionally numb) often reported by patients during SSRI treatment.
The blunting effect may contribute to patients wanting to stop their treatment too early. However, not everyone taking SSRIs will experience the emotional blunting. In addition, this blunting may also be an important part of the therapeutic process by dampening down the negative emotions and distress felt by depressed patients.
One treatment doesn’t fit all
Depression can have many causes, including genetics – which may also affect our response to drugs used for recreational purposes as well as those used for prescription medications. A study in 2022 showed depressed patients have individual cognitive profiles, which doctors may be able to use to help determine which patients would likely benefit from SSRI treatment. However, as yet, there is not enough research to allow for personalised drug treatments.
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While there has been much debate among scientists about how SSRI treatments work, they are effective treatments for moderate and severe depression. A recent study reviewed 21 different antidepressant drugs and found that all of them were more effective when compared to placebo. The first line of treatment for moderate to severe major depressive disorder is SSRIs, which increase serotonin levels in the brain. Importantly, a separate study in 2022 assessed the brain’s serotonin release and found that it is reduced in patients with depression compared to healthy people. Serotonin is involved in a number of cognitive, behavioural and emotional functions.
New approaches
Not all patients with depression respond to psychological treatments or SSRIs and for this reason scientists are searching for other novel treatments. For example, Esketamine is a new drug designed for treatment resistant depression and has recently been approved by the regulatory body in the USA (FDA). It works on a different set of receptors in the brain called NMDA, which are associated with glutamate, a different brain chemical.
For many people suffering from depression, SSRIs improve their condition significantly. It gives them a better quality of life and improves their ability to function in everyday life. It may be that if we are able to detect depression early, we can treat it effectively with psychological treatments only. Science has shown that there are activities and methods, such as exercise, life long learning and social interaction, that can boost cognition and wellbeing. If we use these methods starting from an early age, we may find that in future we have better mental health and wellbeing as a society.
Barbara Jacquelyn Sahakian receives funding from the Leverhulme Trust and the Lundbeck Foundation. Her research work is conducted within the NIHR Cambridge Biomedical Research Centre (BRC) Mental Health and Neurodegeneration Themes and the NIHR MedTech and in vitro diagnostic Co-operative (MIC). She consults for Cambridge Cognition.
Christelle Langley is funded by the Leverhulme Trust.
Gitte Knudsen has been a speaker for H Lundbeck and Sage Biogen. She is also past president of the ECNP and act as a consultant for Onsero, Sanos and Pangea.
She receives research funding from EU, The Danish Research Council and several private foundations provide unrestricted grants for her research, eg, The Lundbeck and the Novo Nordisk Foundation.
