Antidepressant Drugs Might Work by Changing Our Expectations

By Gloria Feng and Robb Rutledge

“Blessed is he who expects nothing, for he shall never be disappointed." — Alexander Pope

The link between happiness and low expectations is an age-old piece of wisdom. Our neuroscience research backs this up, showing that expectations have a strong influence on happiness that is reflected at the level of brain activity.

We are also studying the link between happiness and expectations. The Happiness Project is a citizen science project with a variety of mini-games inspired by classic neuroscience experiments to probe the underlying mechanisms of happiness. Thousands of people have already played, helping our team of scientists develop mathematical equations to predict how happiness changes from minute to minute in a variety of situations.

You may be able to see the importance of expectations for happiness in your own life. You might get a big bonus at work or have many possessions, but if they fall short of what you had hoped for, you can still be unhappy.

Naturally, our expectations change as we learn. Humans have the tendency to return to a stable level of happiness despite major life changes (the “hedonic treadmill”). This effect might be partly due to changed expectations. When rewards are suddenly plentiful, you’re ecstatic for a while. Over time, your expectations adjust to this new normal and your happiness settles down to typical levels. This ability to learn about our environments is both good and bad. We can bounce back from even the most despairing setbacks, but we also have to face the reality that nothing may make us permanently happy.

SSRIs and Learning

What if you could just adjust your learning mechanism a little — could that lead to lasting effects on happiness? Could you acclimate more slowly to positive events, and speed up adjustments to negative events? That way, if you got a big raise at work, the positive events that follow could still be rewarding. If a negative event occurred, you'd reduce your expectations more quickly to a lower floor so future events wouldn't add insult to injury.

In a recent study, a group of neuroscientists at University College London led by Jochen Michely proposed that this is what antidepressant drugs might do (Michely et al., 2020). Selective Serotonin Reuptake Inhibitors (SSRIs) are the most common antidepressant drugs (e.g., Celexa, Lexapro, Prozac). These drugs boost serotonin and reduce depression in many people. One of the defining qualities of SSRIs is their slow-acting nature, improving mood gradually over many weeks.

Motivated by this clue, the researchers investigated the effects of a standard clinical dose of 20mg of the SSRI citalopram. Sixty-six healthy volunteers took a daily oral dose of citalopram or a placebo on seven consecutive days. Participants played a computerized card game where they could decide which risks to take.

Subjects were presented with one of three decks of cards. Unknown to the participants, one was a high deck (higher chance of reward), another was a low deck (lower chance of winning a reward), and a third was an even deck with balanced odds. Participants decided whether to gamble by drawing a card from the deck presented, or choosing a fair coin toss instead. After many such decisions and their outcomes, participants learned by trial and error which decks to play and which to avoid.

Simple games can measure how depression affects learning.

Source: Pixabay/Pexels

The researchers probed how quickly the subjects learned as they tried to maximize their winnings. They found that compared to participants who took the placebo, the participants taking citalopram learned more slowly from rewarding outcomes, and learned more quickly from undesirable outcomes.

The researchers determined that SSRIs probably don’t directly change people’s expectations or mood, which would have an immediate effect. Instead, they adjust how we learn about the world.

In effect, people on SSRIs adjusted more slowly to positive events so their expectations only gradually improved as they experienced more positive events and so rewards didn’t suddenly stop being positive surprises. People on SSRIs adjusted more swiftly to negative events, reducing their expectations and lessening future disappointments. Over a longer period, these subtle changes in how people learn about the world could help to gradually lift mood.

SSRIs Essential Reads

Antidepressant Discontinuation Syndrome: Just the Beginning

The Brain Effects of Therapy, Antidepressants, and Psychedelics

The future of antidepressant drug treatment

Why should we care about developing mathematical theories behind how antidepressant drugs work? If psychiatrists have used these drugs for decades to alleviate depression, shouldn’t that be good enough?

Today, very little is known about the mechanics of complex mental illnesses such as depression and anxiety. Formal rigorous attempts to understand the inner workings of mental illnesses could help improve treatments.

There is no one-size-fits-all treatment for depression: Different individuals respond differently to medications and therapies, and it is challenging for psychiatrists to predict which treatments will be most effective.

Simple decision-making tasks can be highly informative to neuroscientists studying the inner workings of the brain. Today, such tasks have been adapted into fun and accessible mini-games.

Measuring how fast people learn with games might tell psychiatrists which people would respond well to SSRIs without having to wait a month or more to see if mood changes. Studies like this help to give us a better mathematical understanding of how common mental health treatments work and provide clues that can help improve treatments in the future.