Getting the medication right: How personalized treatments can help alleviate mental illness

It is a concern that anyone who has ever had a psychiatric consultation knows all too well. Will the day come when mental disorders are measured, completely or in part, using objective parameters? Will psychiatrists stop interpreting symptoms subjectively, improvising, and prescribing through trial and error? These questions are not simple, nor are they asked in vain. And although they appear to be timid and to have come rather late, they are being asked outside the traditional ivory towers of laboratories, universities, and research circles. But will they ever reach mental health clinics? In order to take a look at the psychiatry of the future, it is necessary to talk about personalized medicine and precision psychiatry.

Personalized medicine is a medical approach that aims to incorporate as many individual parameters or variables as possible into diagnoses and treatments. In other words, going from a generic treatment for anyone who has a specific symptom or disease to one adapted to the individual. It is not something new. The model has always tended to be this way. Hippocrates, in the 5th century B.C., was already working like this, sensing what proportion of blood, phlegm, yellow bile, or black bile was altered in each patient. In the 19th century, Claude Bernard stated: “A doctor is not a doctor for living beings, not even for humanity, but a doctor for the person; and what is more, a doctor for an individual in certain particular morbid conditions, in his idiosyncrasy.”

The incorporation of fully objective variables to this personalization is more recent. A good example of this is the Framingham study, which is a research project that began in the city of the same name in the State of Massachusetts in 1948, and which has not yet concluded! Thanks to its results, cardiologists are able to stratify their patients into different cardiovascular risk groups, and thus predict the probability of events such as a heart attack. To do this, they take into account clinical variables (such as blood pressure), environmental variables (such as smoking) and biochemical variables (such as cholesterol).

Currently, in areas such as oncology, knowing the genetic lineage of the cancer in question is much more useful for prescribing treatment than describing its symptoms or even its exact location. The definition of these groups based on particular biology, defined beyond external symptoms or phenotypes (from the Greek phanein, “to appear,” “to show”), allows us to know what happens to each individual and choose the best treatment for them.

And what role does psychiatry have in all this? Mental disorders and objective measurements. Psychiatry and analytics. But aren’t they both oxymorons? Indeed, the couch has traditionally been associated with the subjective. Starting with psychoanalysis: what does this dream, or this symptom, mean to you? Or, these days, being asked “what is your mood today?” when you enter. This approach is not necessarily bad, nor is it necessarily good. That’s just it: it’s subjective, and also very specific to our times.

On the other hand, in our collective imagination, the laboratory embodies all those parameters labeled as objective: milligrams of glucose per centiliter of blood; millimoles of sodium per liter of blood. All of them are immutable, measured with unquestionable precision, reliability, and validity. They are typical of so many other medical specialties.

This is where precision psychiatry comes in. This term, coined by Dr. Eduard Vieta in 2015, stands as a reflection of this personalized medicine, applied to the study of mental disorders. There are several variables that have come to the fore with a clear message: “I will let you know what is happening to the patient”; “I’m going to tell you how to treat him.” But a lot of the time we cannot trust them. Most have been rejected outright, others have been left aside, and some are still there, trying to persuade us. I am thinking, for example, of genetic analysis techniques, such as cytochrome P450 genotyping, which have been established more or less successfully and are currently used to predict tolerance to certain drugs. I am also referring to polygenic risk scores, in which the influence of hundreds of different mutations on the development of a certain mental disorder is studied. And, on a more mundane level, I also think about all the data that will soon be collected through our smartphones: For example, the quantity and quality of our sleep and our daytime activity patterns.

One way or another, no one seems aware that these immense, almost infinite sets of data will require new and more powerful statistical analysis tools. Indeed, it appears that the time has come for artificial intelligence and the newly arrived computational psychiatry. These tools help can help us interpret what the human mind seems to lack sufficient algorithmic power for.

Now that we have reached the year 2023, scientific progress seems to have reached levels that were unimaginable until recently. One of the most promising lines of research is extracellular vesicles (ECVs), microscopic fat droplets that are constantly released from all the cells in our body and contain molecular information (proteins, nucleic acids, and lipids) from their place of origin. The important point, our “narrative turn,” is that in recent years we have learned how to isolate those that come from the brain, make them “explode,” and analyze their contents. In turn, this provides us with real-time information about what is specifically happening in our neurons: Are they inflamed? Has there been a change in their glucose uptake? Is it rather a problem in the function of their mitochondria, or of any of the cell’s components? The vesicles function as a kind of liquid biopsy, providing us with data directly from our brain. And the thing is that, until now, many of the parameters that we measured in blood were general and systemic, and could be telling us about problems that orginated in other places, perhaps in the kidney or the liver, but always sowing doubt. VECs modify the landscape of variables that we can capture and use, taking us in a direction that is not only more precise in the quantitative field, but also qualitatively different.

In short, this new way of measuring, which is a lot more specific and, therefore, more scientifically valid, will greatly facilitate the transition from psychiatric phenotypes (patterns of thoughts, emotions and behaviors, as when we say “major depressive disorder”) to “endophenotypes” or “biotypes” (our biological characteristics). Thus, by “endophenotyping” patients with mental disorders (especially severe ones), we will be able to classify them into biological boxes and it will be easier (and more consistent) to limit pharmacological treatment. In the future, a blood test may be decisive in determining the right psychiatric medication, which would be a change that, in consultations, could take the following format:

Reason for consultation: “Doctor, I feel so bad that I am unable to leave the house, and we have already tried five drugs.”

The doctor (today): “I understand, let’s change the drug” (the next one on the clinical guide that has been drawn up according to clinical trials designed according to the phenotypes).

The doctor (in a few years): “I understand, let’s run some tests. Let’s analyze your endophenotype and choose the treatment based on the results.”

Is the revolution imminent? I don’t know. But it is evident that there is a new player in the personalized medicine game, and it’s called precision psychiatry. And, although young and inexperienced, it may well have the best hand. So, take a seat and buckle up; the show’s about to start.

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