Prozac, approved in 1987 in the United States, changed the way depression is treated. Its mechanism of action, increasing serotonin levels in the body, led to the hypothesis that mental illness was caused by a chemical imbalance. For many experts, this interpretation supposed a reduction of the stigma that accompanies these ailments. They were no longer a disease of the soul or a character flaw, but a physical disorder, like diabetes, that could be repaired with medication. Pharmaceutical Lilly, which also marketed the first insulin, came to enter with Prozac €2.5 billion a year in the late 1990s.
Since then, the drugs in the Prozac family, known as selective serotonin reuptake inhibitors, have multiplied and their use continues to grow. In Spain, in a trend that it shares with almost the entire world, the consumption of antidepressants increased by 6% between 2020 and 2021, and in the United Kingdom, one in six have received a prescription with this type of medication. A study published in the magazine The Lancet last year it concluded that, during the pandemic, depressive disorders had increased by almost 30% worldwide. The market continues to grow.
Last week, however, a job published in the magazine Molecular Psychiatry questioned the hypothesis that depression is related to a serotonin deficit. The authors, led by Joanna Moncrieff and Mark Horowitz of University College London (UK), conducted an extensive review of studies in which they found no link between low serotonin levels or reduced activity and depression. Nor did they see that healthy people had greater serotonin activity than sick people, and they even found that reducing serotonin levels with drugs did not worsen the mood of the volunteers who participated in these experiments. Moncrieff and Horowitz conclude that “the massive research effort based on the serotonin hypothesis has not produced convincing evidence for a biochemical basis for depression.”
The results and the quality of the study have been largely accepted by the scientific community, which for more than 20 years has questioned the validity of serotonin imbalance as an explanation for a disease as complex as depression. However, the opinions expressed by the authors regarding their results are questioned. Moncrieff and Horowitz, who in an article published in The Conversation recall the use of the serotonergic hypothesis in promotional campaigns for antidepressants by the pharmaceutical industry, suggesting that the main effects of antidepressants have to do with the placebo or with an emotional numbing of patients. If that is so, they say, “it is not clear that they do more good than harm.” In addition, they consider that the biochemical hypothesis, seen at the time as a tool to reduce the stigma around mental illness, makes people not optimistic about the possibility of learning to regulate their moods and recover.
María Portella, head of the Mental Health group at the Biomedical Research Institute of the Sant Pau Hospital in Barcelona, believes that “the results of the study are correct, but the interpretation is exaggerated, because in that study the efficacy of antidepressants is not looked at serotonergic. These types of antidepressants improve mood and are one of the ways to treat depression. It’s another thing if too many people are being treated with those drugs,” she continues. “But to conclude from that lack of relationship between serotonin levels and depression, that [los inhibidores selectivos de la recaptación de la serotonina] they don’t work, it’s not correct”, he adds. And he explains it with an example: the serotonin hypothesis would be as if, seeing that acetylsalicylic acid has a positive effect on headaches, we conclude that the headache is the result of a deficit of that acid. That would be wrong, but proving it shouldn’t make us think that aspirin doesn’t work, he exemplifies. “The fact is that when you do clinical trials with antidepressants, 70% of people improve, which is a figure comparable to other drugs, for diseases such as diabetes or cardiovascular diseases, which we consider effective,” he says.
Many drugs are used in medicine for which the biological mechanism that makes them work is unknown, but it is possible to prove that they are more effective than a placebo by testing them in clinical trials. Víctor Pérez, head of psychiatry at the Hospital del Mar in Barcelona, affirms that in these trials it has been observed that “the effect of antidepressants it’s blunt”. However, it affects the complexity of mental illness and what we call depression and, therefore, of its treatment. “There is no single treatment, and psychotherapy can be as effective as antidepressants in treating depression, but you also have to keep in mind that it takes time and has a cost that makes it less accessible than drugs,” he says. “In life, we all have conflicts of interest. For a psychiatrist who prescribes antidepressants and makes a living from them, doubting their efficacy is outrageous. The authors of this study belong to a group of professionals who defend treatment without antidepressants”, Pérez states as an explanation of the interpretations of some results that go beyond what is reflected in the article published in Molecular Psychiatry.
Víctor Peralta, from the Health Research Institute of Navarra, considers that the researchers make a biased approach with their work. “They exclude from their study depressions such as bipolar, which are precisely the ones with the greatest biological load, in which there is a basic biochemical disorder and those that best respond to antidepressant drugs that raise serotonin,” he says. . “In any case”, continues Peralta, “the clinical reality, the one that those of us who treat patients see, is very eclectic. Antidepressants work, but the response must be accompanied by a psychotherapeutic approach. And the antecedents of the problem are also studied and it is about understanding the context in which depression arises in order to give an adequate response with all that information”. The psychiatrist also affirms that “there are depressions such as monopolar depression that, due to their own characteristics, are recurrent and not only have to do with the patient’s vital circumstances. It is necessary to explain these possibilities of relapse, which sometimes occur due to seasonal alterations, and make a psychotherapeutic and educational approach to teach the patient to detect the first symptoms and also offer antidepressants, which are useful to prevent these relapses”, he concludes.
Until now, mental illnesses such as depression lack biological markers that allow their presence in the body to be detected with a blood or urine test. They are identified by their symptoms and attempts to identify biological factors have had little success and have not allowed the identification of a single mechanism on which to act to correct the problem. This search for material causes and solutions has researchers like Moncrieff at the other extreme, who believe that thinking of depression as a disease of the brain is incorrect. As he wrote in a recent article, “Perhaps our common sense understanding of depression is more useful than the medical one. Our moods and our emotions are almost always reactions to what is happening in our lives. We feel good when things are going well, and sad, anxious, angry, or frustrated when things are going badly,” he stated. In his opinion, the brain is not what triggers these emotions. Poverty, debt, divorce, child abuse, loneliness… “can predict whether someone is going to be depressed or not,” he continued. Helping people understand their problems and face them, through therapy, meditation and even social measures, without the need for drugs, would be the solution for depressed people, according to the researcher. The psychiatrists consulted for this report do not reject this approach, but consider that ruling out the use of antidepressants, with their positive effects in many patients, even though they have limitations, is not a necessary step to effectively apply the methods that Moncrieff defends as exclusive. In the long term, psychiatric illnesses, like all others, will have less individual impact if living conditions improve for the majority. But that takes years or decades that many depressed people can’t afford.