Serotonin syndrome: understanding pathophysiological bases and managing a growing clinical challenge

Serotonin syndrome (SS) is a potentially life-threatening condition resulting from excessive serotonergic activity often triggered by overdoses, drug interactions or inadequate polypharmacy. Serotonin syndrome is often underdiagnosed, and its documented prevalence worldwide is limited, however due to the growing global prescription of antidepressant agents for conditions ranging from psychiatric disorders to chronic pain and sleep disorders, the number of incidences is increasing. Serotonin syndrome presents with a wide spectrum of clinical manifestations, from mild agitation and hyperreflexia to severe hyperthermia, rigidity, and multi-organ failure. Its pathophysiology primarily involves 5-HT1A and 5-HT2A receptors, although other mechanisms may contribute. Current diagnostic frameworks, such as Hunter's criteria, provide guidance but have limitations, especially in cases of polypharmacy. Management strategies focus on early recognition, discontinuation of serotonergic agents, supportive care, and targeted treatments such as cyproheptadine, although its efficacy requires further study. Severe cases necessitate urgent interventions to control hyperthermia and prevent complications like rhabdomyolysis. This review highlights the clinical relevance of SS, its challenges in diagnosis and management, and the urgent need for increased awareness among healthcare providers. Future directions should aim to refine diagnostic criteria, explore novel therapeutic options, implementing preventive strategies and investigate the broader role of serotonin dysregulation in clinical practice to reduce morbidity and mortality associated with this condition.