The composer Héctor Berlioz described in his Memories “the awful feeling of being alone in an empty universe.” In this state, the musician stopped composing, he remained inactive and immobile because he had no other capacity “other than to suffer.” Andrew Solomon says that acute depression is both a destruction (the instinctive functions of life disappear) and a birth (that of a demon). Almost all the testimonies speak of being “on the brink of the abyss,” which can mean hovering around madness or destruction. For those who have not experienced it, it is difficult to imagine. The bad thing is when this devilish situation persists over time and continues despite treatment. What to do then?
The first thing to do is make sure that it really is treatment-resistant depression. The diagnosis must be appropriate, we can never treat blindly. For example, anemia, hypothyroidism or some other hormonal disorder that could justify the symptoms must be ruled out. Therefore, every patient undergoing treatment for depression and anxiety must have at least a blood test and a medical evaluation to rule out these factors. We must also ask ourselves: is the patient taking any medication for another pathology that could cause depression? Does the patient consume any toxic substance that promotes or perpetuates the condition?
Within mental pathology, depression must be differentiated from a bipolar disorder, where antidepressants not only will not be effective, but can worsen the condition, or differentiate it from an anxiety or personality disorder. We will also have to ensure that the therapeutic attempts have had an adequate duration (with antidepressants it should be six weeks) and with good adherence (between 30 and 50% of patients do not take the treatment well). It will give us clues to ask the patient how he responded to treatment in the past.
In its most accepted definition (the lack of response to two therapeutic attempts at adequate times and doses), treatment-resistant depression (TRD) affects 30% of patients. This figure comes from clinical trials in which difficult patients are not entered and where all confounding variables are controlled. In real life, the percentage reaches at least half of the patients, and some factors seem to be associated with this resistance: older age, greater severity of symptoms, coexistence of other mental disorders, cognitive dysfunction (such as concentration or memory), chronic pain or history of trauma. According to the algorithms, the next step is to deploy the different pharmacological tactics that have proven effective: combining two antidepressants with different mechanisms of action, replacing one with another from a different family or enhancing the antidepressant with a different substance.
However, it is not an exclusively pharmacological issue. There are many reasons to incorporate psychotherapy into an integrative approach to depression. Firstly, because it is the therapeutic modality that patients usually prefer; second, because it provides possibilities for emotional learning and the management of personal relationships, and encourages resilience and the search for meaning. Third, because meta-analyses show that adding psychotherapy to pharmacological treatment has a moderate effect (which is not small).
We can try a carousel of antidepressants but it won’t work. In the same way that we can uselessly apply multiple psychotherapy approaches to a patient with severe melancholic depression, in need of a pharmacological approach.”
The most studied therapies are cognitive-behavioral, interpersonal and mindfulness, although it seems that effectiveness does not depend so much on the specific technique as on factors common to the different schools. International guidelines systematically recommend combined pharmacological and psychotherapeutic treatment. Because, when did psychiatry leave psychotherapy aside? The great fathers of psychotherapy, such as Sigmund Freud, Carl Jung, Aaron Beck, Otto Kernberg, Alfred Adler, Viktor Frankl, Eric Berne and Joseph Wolpe, were psychiatrists. And now we have the opportunity to work, side by side with clinical psychologists, to jointly implement this essential therapeutic tool.
But the concept of treatment resistance is sometimes too focused on the treatment and little on the patient’s context. There are depressions that are highly conditioned by the devastating experience of childhood trauma, by oppressive family relationships that perpetuate suffering, or by unbearable jobs. We can try a carousel of antidepressants but it won’t work. In the same way that we can uselessly apply multiple psychotherapy approaches to a patient with severe melancholic depression, in need of a pharmacological approach. Broadening the focus is essential.
Finally, there are third or fourth line options that can provide great hope for the patient and their families. Electroconvulsive therapy, despite its terrible reputation, has demonstrated robust effectiveness in resistant depression. It is carried out under anesthesia and in neat and controlled conditions, so we will have to banish the outdated sequences of Some one flies over the cuco’s nidus. Transcranial magnetic stimulation is usually better accepted by patients; It has promising evidence, but it is little available in our country. Recently, drugs such as ketamine or esketamine (marketed in Spain) have appeared, with novel mechanisms of action and rapid and, apparently, sustained efficacy. They are expensive drugs, which should be applied judiciously and responsibly, in patients with a clear indication. In Australia, psilocybin, another psychedelic, has just been marketed, which is generating high expectations.
In this sense, the contribution of new tools from the pharmaceutical industry is great news. Perhaps some naive people still wonder: are pharmaceutical laboratories NGOs? Definitely not. Just like Ikea or Zara, they are companies that want to make money. But if they are well regulated and monitored from an ethical point of view, they are essential agents in our health system. In my opinion, it is just as wrong to uncritically buy all their commercial messages as it is to demonize the entire industry as a whole, in a story that is somewhere between conspiratorial and anti-capitalist. The pragmatic and reasonable thing is to align its legitimate interests with those of society, which urgently needs scientific advances, both in vaccines and drugs.
To the patient, who is the one we care about, we will tell him that we will not sit still, that there are many options and that we will do what is in our power. From many perspectives, with the help of diverse professionals, with a single objective: to glimpse, with the help of the famous quote by Albert Camus, that in the middle of winter there is an invincible summer, and not lose hope.