Debunking the Serotonin-Depression Theory (with Psychiatrist & Professor Dr. Joanna Moncrieff)

In this podcast (episode #415) and blog, I talk to psychiatrist, researcher, professor and best-selling author Dr. Joanna Moncrieff about her new study on the chemical imbalance myth, antidepressants as placebo, the causes of depression, how to withdraw from psychiatric drugs, and so much more.

As mentioned in my interview with journalist and mental health advocate Robert Whitaker and my previous interview with Dr. Joanna Moncrieff, the chemical imbalance theory has been around for a long time. From the 1970s, drug companies and many mental health professionals have largely marketed psychiatric drugs as anti-psychotic, anti-depressive, or anxiolytic (anti-anxiety)—cures combating a particular disease, notwithstanding the lack of evidence for chemical imbalances or other pathologies related to mental illness. This was recently highlighted in the groundbreaking systematic review study led by the psychiatrist and researcher Joanna Moncrieff, Mike Horowitz and their team. 

As Moncrieff and Whitaker point out (alongside many other mental health professionals and advocates), the chemical imbalance approach is shaped by the assumption that symptoms of depression and other mental health issues are caused by a brain chemical abnormality, and that psychotropics like anti-depressants help rectify this abnormality and improve mental health.

Even though this hypothesis currently dominates the way we think about mental health, we have no evidence that it is the best way to understand mental issues, as Moncrieff points out in her study on the serotonin theory of depression. First, there is no strong evidence that depression, for example, is associated with any particular biochemical abnormality. Moreover, we do not know if the drugs we use work in this way, i.e. correcting biochemical imbalances. This is due to the fact that the mental health drugs we use are psychoactive. They cross the blood-brain barrier and change the normal state of the brain, which means they can change our feelings, thoughts, perceptions and even behaviors, just in the same way a substance like alcohol can. For instance, alcohol may decrease someone’s social anxiety, but this does not mean it is a “cure” for social anxiety. Many psychotropics work the same way, including antidepressants—we have been lied to for decades.  

As Moncrieff and the other authors of the study note in their article in Molecular Psychiatry, “the main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.” If we do not have good evidence that psychiatric medications like antidepressants do not work by correcting or reversing a chemical imbalance in the brain that causes depression, it is important that we review the way we use their drugs, many of which may even cause chemical imbalances in the brain.  

Joanna takes a different approach—what she calls the “drug-centered” model. This centers around understanding what prescribed psychiatric medication is doing in the brain and body, and how it is changing the state of the brain like a substance such as alcohol does. We need to understand the kind of alterations these drugs make and factor them out of the equation—we cannot simply say that they are targeting and “correcting” a hypothetical biochemical imbalance. For example, benzodiazepines are currently used to treat anxiety. These drugs, when given to someone in a high state of arousal, can help calm down the brain and body. Yet they also do the same for someone who is not anxious—they alter the brain by reducing brain activity. There is no strong evidence that these psychoactive drugs are “curing” anxiety. 

To understand psychoactive drugs and their use in mental healthcare, we first need to understand their general effects in people, including individuals who do not have depression or symptoms of another mental issue. Yes, some people may see these mind-altering effects as an improvement, but not everyone. This may account for the very, very small difference we see between drugs like antidepressants and placebo in randomized control trials (the gold standard of evidence-based medicine). Yet it is also important to consider the negative outcomes that often occur when a person comes off these drugs—withdrawal symptoms can be incredibly traumatic mentally and physically, and last for a long period of time.   

The chemical imbalance theory about depression is about more than just someone’s brain chemistry. It impacts their sense of self; how they see themselves. It tells someone that the problem mainly resides in their brain, and that there is something intrinsically wrong with their biology, which is a great burden to put on someone who is suffering, especially since there is no scientific evidence to support this hypothesis. This kind of mindset is also less likely to make someone think that their own efforts or anything besides medication can affect their recovery, which can impact their healing in the short and long-term. 

Depression is not as simple as a “brain disease”. Human brains and bodies are way more complicated than that. Of course, things are going on in the brain when people are feeling depressed. Everything we do is mediated by our brains, whether we are walking, working, feeling, eating, exercising and so on. This does not mean that we can fully understand depression at the level of the brain. Depression is an emotional reaction that is affected by our history, personal inclinations, and so on. It is, at its heart, a reaction to life circumstances mediated by our uniqueness. This means that, to understand depression, we need to understand both the circumstances it is a reaction to and the individual’s personality, history and development (everything that has happened to them).  

One of the most important things we can do to help people who are depressed is to find ways to help them address their unique life circumstances, not just give them a drug and send them on their way. That is not to say that there is no such thing as severe depression or that people with depression do not suffer greatly, or even that psychiatric drugs do not work for some people over a set period of time. But, unfortunately, we do not have any good evidence that even severe depression responds well to psychiatric drugs or other interventions just at the level of the brain.  

It is so important that we understand the nature of the psychiatric drugs we are using. They are not harmless, as Moncrieff talks about in detail her book A Straight Talking Introduction to Psychiatric Drugs: The truth about how they work and how to come off them. Drugs like antidepressants have a blunting effect that may help some people for a certain period of time, as mentioned above, but other people may find this effect incredibly unhelpful, especially if they are experiencing many unwanted side effects. Additionally, although blunting someone emotions may be helpful in the short term, it is not a long term solution that will help someone find true and lasting healing.  

Moreover, the longer someone is on these drugs, the greater chance that their withdrawal effects will be more significant and last longer. In Joanna’s blogs, she points out that this is why it is so important to understand how these drugs affect the mind and brain, so that you are more empowered to know what choice will be best for you and your unique circumstances. Some people may find these drugs very beneficial in the short term; however, it is important to understand how these drugs can be dependence-forming in the long term.   

This is why you cannot just stop using these medications overnight. It is important to remember that withdrawal should always be done under the supervision of a qualified professional. Take your time, process the information in this podcast and blog, speak to those you trust and the appropriate medical professional. These drugs can alter brain chemistry, and withdrawal can be an incredibly difficult process. The brain adapts to the presence of these drugs. Even if you do not feel a “high” from a drug, this does not mean you cannot become dependent on it.  

People usually don’t take these psychoactive drugs for a few days or weeks. They generally take them for months or years, often based on research done on the long-term effects of psychiatric drugs like anti-depressants, called “relapse prevention trials”. These trials look as if they are examining the benefits of long-term treatment, but what they are actually doing is enrolling people that have already been using these drugs for years, then randomizing them to either continue the treatment or be weaned off (usually very quickly) onto the placebo. The latter group often experience intense withdrawal effects, since these drugs alter brain function and chemistry. However, in the trials, these withdrawal effects are often assumed to be because of the “brain disease”. This can make someone feel terrible or believe that there is something intrinsically wrong with them, even though what these research studies are actually studying is not the benefit of long term treatment but the adverse effects of withdrawing from these psychoactive medications quickly. Very few studies try to wean people off these drugs gradually, and even these still have a risk of significant withdrawal effects that bias the clinical data.    

If you do decide you want to go off these drugs, it is important to take a flexible approach, and avoid switching between certain drugs, especially anti-depressants, as much as possible (anti-depressants are often quite different from each other). It is important to note that it is easier to reduce higher doses than lower doses; for lower levels, people often use tapering strips or liquids with the help of a professional to reduce the drug by very small amounts over a specific period of time. 

Moncrieff uses these methods in her London clinic, which she is hoping to expand into other areas of the UK and perhaps the world. Moncrieff and her team also want to try to set up a peer-support group to help other people trying to withdraw and find hope. Thankfully, there are also great sites like Mad in America, Rxisk, ISEPP and other patient-run websites that seek to provide people with helpful information and address all parts of the human experience, not just our biology.   

For more on the chemical imbalance myth, antidepressants as placebo, the causes of depression, and how to withdraw from psychiatric drugs, listen to my podcast with Joanna (episode #415), and check out her recent study and her work. If you enjoy listening to my podcast, please consider leaving a 5-star review and subscribing. And keep sharing episodes with friends and family and on social media. (Don’t forget to tag me so I can see your posts!).     

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Podcast Highlights 

3:30 The new study on depression everyone is talking about  

5:50 How antidepressants really work 

10:00, 29:00 What the drug-centered approach to psychiatry is & why it is so important  

12:00, 16:07 Antidepressants compared with placebo: what we see in the randomized controlled trials data 

18:50 The chemical imbalance myth: why it is so worrying 

20:00 Depression is not as simple as a brain disease 

25:00 Why informed consent is a huge issue in psychiatry

27:45 Psychiatric drugs are not harmless, which is why it is so important we understand what they do & how they can affect us 

36:50 Young adults & antidepressants 

40:05, 52:00 Withdrawing from psychiatric drugs

56:00 Psychedelics & mental health 

Switch On Your Brain LLC. is providing this podcast as a public service. Reference to any specific viewpoint or entity does not constitute an endorsement or recommendation by our organization. The views expressed by guests are their own and their appearance on the program does not imply an endorsement of them or any entity they represent. If you have any questions about this disclaimer, please contact    

This podcast and blog are for educational purposes only and are not intended as medical advice. We always encourage each person to make the decision that seems best for their situation with the guidance of a medical professional. 

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