Resistant depression calls for a paradigm shift with more precise diagnoses

The increasing percentages of treatment-resistant depression (TRD), —between 35% and 37% of people with depression worldwide—, highlight the limits of current models of care and the need to move towards more precise and personalized medicine.

This is the main message that is extracted from the III Conference on addressing treatment-resistant depression, organized by the Sant Joan de Déu Health Park with the aim of bringing the reality of this disorder closer to society from the direct experience of the people who live with it. Precisely with this intention, some witnesses who have suffered the consequences firsthand have joined the SJD Health Park to promote a paradigm shift that they consider essential to have more precise diagnoses and personalized interventions.

From 100 to zero in a flash

First-person accounts have demonstrated the profound impact of resistant depression and the difficulty of finding effective treatment.

Javier, a recovered patient, explains how he "lost the will to live" suddenly, for no apparent reason, after years of active living. His perception is that he went “from 100 to zero in the blink of an eye.” After various unsuccessful treatments, he was diagnosed with depression and began a specialized approach that has allowed him to recover his life. Javier knows that depression will return and says he is prepared to identify its symptoms and be able to intervene quickly to achieve an effective result in less time.

On the other hand, Loli, the mother of a patient with depression for more than twenty years, calls for early diagnosis and specialized care from the beginning: “If we had gotten there earlier, maybe it wouldn't have become chronic,” she says. The "journey" that your son went through until he was diagnosed is like a slab of stone in front of the "helplessness" that the caregiver feels in the face of such a devastating diagnosis. Both stories agree on the same idea: Resistant depression is a long, complex process that is often misunderstood by society, and requires an approach tailored to each person., to reduce the waiting time until the expected effectiveness is achieved.

As many depressions as people

The expert professionals at the Sant Joan de Déu Health Park insist that depression is not a homogeneous disease. It is a disorder that combines biological, psychological and social factors. “There are as many depressions as there are people,” they summarize. This complexity explains why treatments do not always work uniformly and require a comprehensive approach capable of intervening in all personal areas.

From trial and error to precision

Currently, the treatment of resistant depression is often based on trial and error processes of different treatments and approaches, guided by objective but also subjective clinical criteria. This model, as professionals explain, has clear limitations and can prolong the suffering of those affected.

Faced with this scenario, specialists propose a paradigm shift towards a precision psychiatry, which allows for better adjustment of diagnoses, identification of the type of depression and application of the most appropriate treatment from the beginning. "It's not about changing all the parts of the car, but about identifying exactly what's wrong and how to repair it, taking into account the experience of the driver (the person's life) and the road they drive on (the environment)," explains the psychiatrist at the SJD Health Park, Salvatore Aguilar.

A comprehensive model with promising results

The Sant Joan de Déu Health Park has developed a Treatment-Resistant Depression Unit with a comprehensive and personalized approach model, which combines different advanced therapeutic options, according to the profile of each patient, which seek to stimulate the neuroplasticity of the brain and which are applied in safe clinical environments and under specialized supervision:

• Intranasal esketamine
  Administered in controlled sessions, it acts quickly on brain circuits involved in depression. It is especially useful in cases where conventional antidepressant medications have failed. Patients receiving these treatments achieve the greatest neuroplasticity gains, especially when combined with psychotherapy. It has shown a positive response in 82% of patients.
• Electroconvulsive therapy (ECT)
  A technique with decades of scientific evidence, indicated for severe and resistant depression. It is performed under anesthesia and medical monitoring, with very significant results in reducing symptoms, between 85-90%.
• Transcranial Magnetic Stimulation (TMS)
  Non-invasive procedure that uses magnetic fields to stimulate specific areas of the brain related to mood. It allows improvements without serious side effects and has shown a 35-40% response.
• Psychotherapy and comprehensive approach: nursing, psychology, social work and family support.
• Psychedelic treatments (research in a clinical setting)
  In an experimental phase and under strict protocols, these treatments seek to unlock mental patterns and facilitate psychotherapy in patients with chronic depression. Some of the patients in the Resistant Disorders Unit are candidates to participate in this trial.

Since its launch (2025), it has treated 205 people, of whom 190 have improved or recovered. 80% of patients are discharged in less than 12 months and with an average stay of six months. The results show a significant increase in improvement in quality of life of the people served. Younger patients or those with a shorter duration of the illness tend to respond more quickly to treatment.

Treatment selection is a personalized process based on scientific evidence.. The unit's professionals assess the clinical characteristics of each patient and explain all possible scenarios, taking into account factors such as the presence of psychotic symptoms, motor slowing, comorbidities and contraindications. It is a model of shared decisions, where the patient, with the support of the family, chooses the option they prefer from among the specialists' proposals, which range from less to more invasive: esketamine, Transcranial Magnetic Stimulation (TMS) and Electroconvulsive Therapy (ECT). This approach ensures treatment tailored to each case while respecting individual preferences.

Beyond treatment: psychotherapy and continuity

Experts emphasize that biological treatments are not enough on their own. Recovery requires continued psychotherapeutic work, monitoring after the intensive phase and intervention in the social and family environment. Without this continuity, the risk of relapse is high.

Within the framework of the III Conference on Addressing Treatment-Resistant Depression, held today, professionals from different centers have agreed that the future is about gaining precision. The presentations highlighted the potential of treatments such as esketamine and neuromodulation, the need to adapt them according to each patient's profile, the key role of psychotherapy and the importance of reconciling the brain and life experience. Everything points to a shared consensus: Current treatments are effective, but they could be even more accurate if better diagnostic tools were available.

In this context, professionals point out the need to incorporate technologies such as neuroimaging into clinical practice. Having a better "picture" of the brain would allow us to refine the diagnosis, identify the affected circuits and direct treatment more directly. The goal is to move towards an increasingly personalized treatment: a "custom-made dress" for each person.

Professionals point out that the challenge is not only clinical, but also organizational. We need more continuity of care, reorganizing resources and investing in innovation. “It's not just about having more tools, but using them more precisely and adapting them better to each patient.”

Find more information about depression on the website Saint John of God WE ARE Mental Health 360.