Depression Isn’t Caused by Low Serotonin. So, Do We Ditch Antidepressants?

Sep 12, 2022

Recent research from UCL presented that there was no clear evidence that low serotonin levels cause depression
Does this mean antidepressants are useless? Not necessarily, argue psychotherapists Graham Johnston and Matt Wotton
If you are struggling with depression, find a therapist here

It’s been a long-standing debate in the field of psychology. Psychiatrists on one side quote research to show that antidepressants, and specifically selective serotonin reuptake inhibitors (SSRIs like citalopram and Prozac) have excellent results in treating low mood.

On the other side, psychologists and psychotherapists stress the impact of real-world events (poverty, stress, trauma) and internal struggles (lack of motivation, loneliness) as causes for depression.

This is important. Depression is the most common mental health problem worldwide. We need to get better at understanding and treating it. And antidepressant use is rising fast - the number of prescriptions in the UK doubled in just ten years, between 2008 and 2018.

You might have seen the press coverage of the most recent research from the team at University College London led by Dr Joanna Moncrieff that seemed, at first glance, to settle the issue once and for all. The study was an umbrella review of studies over the last 50 years into the efficacy of SSRIs in treating depression. The review found “no clear evidence” that low serotonin levels cause depression.

The Guardian quoted Moncrieff as saying “[i]t is always difficult to prove a negative, but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin.”

In addition, we know that antidepressants cause side effects for some people like nausea and insomnia, and withdrawal effects. We obviously don’t want to give tablets to people when a) we don’t know exactly how they work; b) we’re not sure they do work; and, c) we know that for a some people they cause harm. We also know that psychotherapy works in treating depression, especially treatments recommended by the National Institute for Health and Care Excellence (NICE) such as Cognitive Behavioural Therapy (CBT).

It seems self-evidently obvious, too, that depression is more complicated than a specific chemical imbalance in the brain. We see people around us responding to events in their lives and struggling to make it out of the fog.

We have known for decades that SSRIs change serotonin levels pretty much immediately but take at least a couple of weeks to make a difference to mood (although, annoyingly, the side effects kick in pretty much straight away). If depression was simply caused by serotonin levels, they’d begin to work on mood levels within hours, not weeks. Many of us are inherently sceptical of Big Pharma, too - often with good justification.

But let’s look a bit more closely at the review by Moncrief and her team. What it didn’t claim was that antidepressants, including SSRIs, don’t work. Instead, it examined the specific ways SSRIs work - by reducing the “reuptake” of serotonin in the brain, thereby increasing serotonin levels. But it’s been common knowledge for decades in the field that the “serotonin hypothesis” isn’t a good explanation for depression. The Royal College of Psychiatry criticised the paper. As part of that criticism, Professor Gitte Moos Knudsen from Copenhagen University Hospital said, “it is largely accepted that depression is a heterogeneous disorder with potentially multiple underlying causes.” This is often described as the “biopsychosocial” model that acknowledges the biological, psychological and social impacts on mental health, one that the vast majority of the field of psychology ascribes to now.

One classic metaphor is with headaches. We don’t think that a lack of paracetamol causes headaches (lots of other things might be the cause such as stress, dehydration, too much sunlight etc.), but we take a pill and have a reduction in the pain in our heads. Similarly, we don’t need to believe that serotonin levels cause depression to believe that SSRIs can work to improve mood.

It’s certainly possible, and maybe even likely, that some people have a specific kind of depression that is linked to - not necessarily caused by - changes in the serotonin system. Also likely is the idea that because antidepressants affect a number of different pathways and receptors in the brain, they help people with a range of different types of depression, only some of which are linked to the serotonin system. Some types of depression seemed to be linked to a loss of connectivity between synapses in the brain, which SSRIs (and therapy, of course) can help counter.

Depression is best treated holistically. The current evidence suggests that a combination of antidepressants and therapy (with supportive behaviours such as exercise) is the best plan for the treatment of moderate and severe depression. The medication can help improve mood and raise motivation levels to a point where people can engage more proactively with their therapy to a point where it becomes a virtuous circle. It should be acknowledged, though, that “routine use” of medication is not recommended for treating mild to moderate depression.

In short: depression isn’t caused by low serotonin. But we’ve known that for decades. And antidepressants work for many people, especially in partnership with good therapy.

Graham Johnston and Matt Wotton are both verified Welldoing psychotherapists, and co-founders of the London Centre for Applied Psychology