It's not about the Serotonin

“So, it’s about serotonin. Low levels cause depression and these medications help to restore serotonin to it’s normal level.” 

“But doctor, the paper’s said it’s nothing to do with that and these drugs won’t work.” 

The patient pulls out a copy of Daily Mail: “Depression ‘is NOT caused by low serotonin levels’: study casts doubt over the widespread use of potent drugs designed to treat chemical imbalance in the brain”. The patient looks up expectantly…

“Well, um, see the thing is… Er, it’s complicated…” 

Complicated because for years the medical community has been pedalling the serotonin hypothesis of depression. We still teach it to students and patients. 80% of the public believes in the concept. And why not? It’s convenient. It makes sense. And most importantly it justifies SSRIs. 

Except the latest research suggests this theory is completely wrong.

This study, published in Molecular Psychiatry journal two weeks ago, was splashed all over news outlets. The authors from University College London performed a systematic umbrella review – a ‘mega-review’ including existing systematic reviews and meta-analysis on serotonin and depression.

Studies examining serotonin levels failed to demonstrate any difference between people diagnosed with depression and those without. Serotonin receptors and transported had only weak and inconsistent data showing any link with depression and may have been biased by the use of antidepressants in participants, and artificially lowering serotonin levels through dietary manipulation in healthy people does not result in depression.

The authors concluded the data found no support for the serotonin hypothesis and that “patients should not be told that depression is caused by low serotonin or by a chemical imbalance”.

Of course, this finding will not come as a surprise to most of us. We appreciate that depression is different things, for different people. Indeed, experts agree – depression is a heterogeneous disease with potentially multiple underlying causes, not a single disease caused by a biochemical deficit. 

The Royal College of Psychiatrists and NHS patient information on depression makes no mention of chemical imbalances, instead counselling that a few common causes include life events and personal circumstances, physical health problems, childhood trauma, alcohol and drug use, and genetic factors. 

Nevertheless, not all experts agree that serotonin has no influence on depression. Because this review considers depression as a single disorder it cannot educate us on the different causes so it remains possible that a subset could be due to a problem with serotonin. This review suggests certainty, much of the research community still feels the jury is out.

The most frustrating interpretation of this umbrella review being pedalled by the media is that if serotonin plays no role in depression, medications based on altering its action must be ineffective. This is faulty logic.

8 million people in the UK currently take SSRIs. Yes, that figure is terrifying and the latest NICE guidelines on depression encourage clinicians and patients to move away from relying on medications to treat less severe depression (we’ll be covering this in detail in the upcoming Autumn Winter 2022 Hop Topics course). But can 8 million be wrong? Are SSRIs completely ineffective? No, they’re not. Data with the highest level of evidence has confirmed that antidepressants are efficacious and more so than placebo (albeit modestly).

So, yes, it’s time to stop telling patients depression is due to low serotonin levels and that medication corrects this imbalance. Time to admit we don’t understand how antidepressants work, but at least we know that they do, at least some of the time. It may not be much, but at least it’s the truth.