From depression to schizophrenia: the answers of 'precision psychiatry'

Resistance to treatment is one of the most relevant issues that emerged during the proceedings of our 50th Congress of the Italian Society of Psychiatry, which ended a few days ago in Bari. For millions of people with major depression, schizophrenia and obsessive-compulsive disorder, finding the right treatment remains complex and exhausting. Despite medical progress, a significant percentage of patients - 30% to 60% depending on the disorder - do not get an adequate response after correct treatment cycles. A real 'wall' that amplifies the health burden and personal frustration, but which should not be regarded as impenetrable or as a therapeutic failure.

Resistance occurs when a patient does not achieve satisfactory clinical improvement after at least two different cycles of standard treatment, conducted with appropriate doses and durations. However, this definition risks oversimplifying a phenomenon that depends on biological, psychological, social and relational factors. Dealing with it requires a paradigm shift: not simply adding another drug, but adopting a broader, tailor-made vision to turn the wall of resistance into a gateway to recovery.

In the field of depression, up to 30% of patients have resistant forms. In many cases, non-response is related to inadequate treatment or poor adherence rather than intrinsic drug inefficacy. In these contexts, treatments need to be reassessed and, if necessary, supplemented with augmentation strategies, structured psychotherapy or non-pharmacological techniques such as transcranial magnetic stimulation (Tms). As of 2019, esketamine, indicated in combination with an oral antidepressant in adults with major depressive disorder unresponsive to at least two properly used antidepressants, is also available in Italy.

In schizophrenia, resistance affects about one third of patients. Clozapine continues to be the gold standard in resistant cases, although it is still underused due to concerns about side effects. However, recent changes to blood monitoring programmes, both in the US and Italy, have simplified management and improved access to treatment, while maintaining the necessary clinical controls. Alongside medication, evidence-based psychosocial interventions, such as family psychoeducation, social skills training, cognitive rehabilitation and psychotherapeutic approaches targeting persistent symptoms, remain central.

This pathology presents the highest rates of resistance: 40-60% of patients do not respond to Sssri, which is the first-line treatment. In resistant cases, combinations of augmentation strategies and non-invasive neuromodulation techniques - including Tms and vagal stimulation - represent particularly promising directions of research.