Abstract The “Mad Protocol Syndrome” is a condition in physicians who rigidly or normatively apply clinical guidelines or protocols. This syndrome, understudied but widespread, is seriously dangerous because it generates iatrogenic effects, promotes polypharmacy and drug interactions, is frequently based on controversial, unsound, and rapidly changing foundations due to the rapid emergence of new studies, fails to consider patient-centered care, is not developed collaboratively by medical specialties and patients, is often influenced by powerful interest groups (such as the relationship of almost all panelists on clinical guideline development committees with the pharmaceutical industry), always maintains an exclusively biomedical perspective ignoring broader biopsychosocial viewpoints, and because there are hundreds or thousands (or perhaps millions?) of clinical guidelines that contradict each other in their recommendations. The patient is a biographical, social, and spiritual reality, never an isolated analytical value. No laboratory target (HbA1c, LDL, or blood pressure) justifies destroying a human being's autonomy, lucidity, or daily well-being. "The Mad Protocol Syndrome" ultimately represents the dehumanization of medicine through bureaucracy. To break this absurd cycle of over-prescription and alienation, 21st-century medicine doesn't need to generate more guidelines from distant experts, but rather urgently reclaim the sovereignty of clinical judgment, safe deprescribing tools, and critical methodological approaches that return control to the primary care physician and dignity to the patient. Studying and reflecting on these concepts is the first step toward transforming clinical practice and rescuing the humane, critical, and sensitive medicine that patients so desperately need. After 10 chapters where 10 very frequent clinical scenarios of modern medicine have been presented, showing the alarming reality of the “Mad Protocol Syndrome”, below we move towards the final synthesis, presenting the principles of a medicine that protects against "Mad Protocol Syndrome." Keywords: Guidelines; Methodology; Applicability, Evidence-based medicine; Patient-centered; Personalized medicine, General practice Introduction Clinical practice guidelines provide evidence-based recommendations to optimize patient care, while protocols dictate rigid, step-by-step procedures. In general medicine, these tools are designed to reduce practice variation and translate complex scientific research into actionable, patient-specific encounters (1, 2). However, clinical guidelines face significant systemic challenges. Key problems include a one-size-fits-all approach that fails to account for individual variations, a lack of universal applicability, and potential conflicts of interest. Misuse of guidelines can sometimes lead to suboptimal care (3-5). The concept we describe as the “Mad Protocol Syndrome” perfectly defines the phenomenon of the tyranny of clinical guidelines or normative biomedical reductionism. This refers to the growing concern that modern medicine focuses too rigidly on treating isolated biological pathways and rigid, one-size-fits-all algorithms. This severely limits personalized care and ignores the complex, multifaceted realities of human illness (6). In the scientific and critical medical literature, promoted by movements such as Choosing Wisely, evidence-based medicine without conflicts of interest, and quaternary prevention (7-10), there are blatant examples of guidelines that exhibit these characteristics: medicalization of risk factors, rigid objectives that induce massive polypharmacy in patients with multiple pathologies, a high rate of panelists with conflicts of interest with the pharmaceutical industry, and a complete disconnection from the biopsychosocial model. After 10 chapters where 10 very frequent clinical scenarios of modern medicine have been presented, showing the alarming reality of the “Mad Protocol Syndrome”, below we move towards the final synthesis, presenting the principles of a medicine that protects against "Mad Protocol Syndrome." The "Mad Protocol” Approach. Criteria of the "Mad Protocol": 1. Iatrogenesis: systemic, due to rigidity, generation of polypharmacy, overdiagnosis, generation of prescription cascades, drug-drug interactions, massive medicalization, and a purely biomedical perspective. 2. Controversial, ineffective, weak, changing, and biased foundations. 3. Use of fixed and obsolete analytical criteria. 4. Contradiction in recommendations between guidelines. 5. Conflicts of interest, implicit commercial interests, and industry interests, sometimes massive. 6. Lack of patient-centered care. 7. A purely biomedical perspective. Lack of a biopsychosocial perspective, biomedical perspective versus genuine well-being, pathologization of life by an extreme biomedical view 8. Lack of a community and participatory app
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