It is known that the effectiveness of drug treatment for depression, ammine deficit based, is largely unsatisfactory. In this review, we examine the proposal of a precision therapy has emerged and has received a strong push by the identification of the role of inflammation in depression. However, precision psychiatry risks being caught in the reductionist trap of searching for the molecular switch that resets the whole system and switches off the disease. This is an illusion since the human being is complex and depression is a systemic and variable disorder. In this study, we show the inadequacy of the reductionist paradigm, and, at the same time, illustrate the superiority of the systemic paradigm centered on psychoneuroendocrineimmunology (PNEI). According to the PNEI paradigm, depression is a disease of the whole human being, caused by different sources working together: psychological, biological, and behavioral. This means knowing the biological and psychological history of the subject, identifying relational and biological crisis factors, and building personalized treatments targeting those factors with the tools of medicine and psychology, which are not reducible to the combination of drugs and psychotherapy. Our proposal presents a paradigm shift that is both theoretical and practical, which enables clinicians to assess patients experiencing depression in a unified way and treat them in an integrated manner.
