The study that shatters explanations of the causes of depression. And shake the pharmaceutical industry

©©Fred TANNEAU / AFP

Atlantico: You have just published a study challenging the thesis that depression is caused by a lack of serotonin in the brain, which offers a new perspective on the use of pills to fight depression. How is the use of these pills based on a “false belief”? Why is there no link between serotonin levels and depression?

Joanna Moncrieff: We looked at all the major areas of research that have investigated the links between serotonin and depression over the past three decades. We looked at six areas in particular: levels of serotonin in the blood, levels of the major breakdown product of serotonin in the cerebrospinal fluid (the fluid that surrounds the brain), serotonin receptors, protein serotonin transporter (the protein that extracts serotonin from the synpase where it is active – this is what SSRIs act on), the experiments that measured the mood of volunteers after reducing serotonin using a special drink and genetic studies of the serotonin transporter gene. None of this research has provided convincing evidence of an association.

Modern antidepressants were thought to work by correcting a serotonin deficiency in people with depression, but we have shown that there is no serotonin deficiency. Many people have been told that depression is caused by a chemical imbalance and that antidepressants work by correcting it. This idea is not supported by scientific evidence.

Is the theory of chemical imbalance as an explanatory factor of depression, and therefore as a means of combating it, totally erroneous?

The theory that depression is linked to an abnormality in serotonin is not supported. We did not review research on other brain chemicals, but the serotonin hypothesis is one of the most studied. It is generally agreed that, for example, there is no strong evidence to support the theory that depression is linked to norepinephrine deficiency, which was a popular theory before that of serotonin.

If your study definitely excludes serotonin, what explanations should be considered?

We can continue to look for the biological causes of depression, or we can look at depression from another angle – we can see it as a reaction to social and personal problems and adverse life events. Many researches show that there is a link between these and depression.

Before your study, other researchers had warned against this absence of link? Why were they not listened to?

Good question. The academic community has known for years that the evidence for a link between serotonin and depression was weak and inconsistent, even though no one had previously gathered the evidence in a systematic way like we have now. I think psychiatrists don’t want to shake people’s faith in antidepressants. In addition, the chemical imbalance theory provides a simple and concrete explanation for situations that can be very complicated and difficult (for a very anxious and unhappy person), which is probably attractive to some doctors and patients.

Is the use of pills to fight depression symptomatic of a medicine that applies a medicinal solution to each discomfort? Has the use of such drugs led to side effects that could have been avoided?

Yes and yes! The problem is to think of depression as a condition that originates in the brain. If you think about it this way, it makes sense to apply a medical solution (we have a saying in English: “when you have a hammer, everything looks like a nail”). But if you consider it to be a reaction to social and personal difficulties, then the most important “treatment” is to help the person cope with these difficulties.

Many people today say that antidepressants have been shown to work, and it doesn’t matter how they work. But I think the “how” is important. When people say antidepressants work, they mean they’re a little better than a placebo in randomized controlled trials, but there are many possible explanations for this. They may have amplified placebo effects (because people can see they are taking the active drug compared to the placebo) or it may be because antidepressants cause emotional blunting. If they act as amplified placebos or dulling emotions, taking them is probably not a good thing, at least not for most people in most situations.

So, in my opinion, there is very little justification for their use and a large number of people have been exposed to their side effects without real benefit.

Has the pharmaceutical industry pushed for their use?

Yes, in the 1990s and 2000s, the industry heavily promoted the idea that depression was a chemical imbalance and that antidepressants corrected it. It is less involved today because most antidepressants are no longer under patent.

How did we come to such a situation? Has there been massive misinformation for many years?

The misinformation came from the pharmaceutical industry, but no one in the scientific community chose to question it. Indeed, many doctors continued to promote the idea that depression was a chemical imbalance, either because they believed in it themselves or because they thought it was a useful message to convey to patients. A prominent psychiatrist, Wayne Goodman, called it a “useful metaphor” (quotes are in my other article attached to this answer).

Do we now have other ways to fight depression without affecting our chemical balance?

In my opinion, we need to look at depression from a different angle. It is not a brain problem, but an emotional response to personal and social difficulties. We need to help people deal with the particular difficulties that led them to be depressed – it’s different for each person. Some people may benefit from therapy, but others may need marriage counseling, employment support, or help with housing or finances.