Agnieszka Zelek-Molik ¹ Ewa Litwa ^2*

• ¹ Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
• ² Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

Mood disorders, such as major depressive disorder and bipolar disorder, are among the most common mental illnesses and a leading cause of disability worldwide. Key symptoms of these conditions include a depressed mood or anhedonia, sleep and psychomotor disturbances, changes in appetite or weight, and fatigue or loss of energy. Prolonged cognitive disturbances further impair the ability to think or concentrate and are often accompanied by persistent feelings of worthlessness or excessive guilt. Collectively, these symptoms underscore depression as a serious, long-term global health issue.In addition, clinical studies indicate a growing number of patients experiencing difficulties in responding to treatment, even in the long term. This phenomenon poses significant challenges for healthcare professionals, families, and patients alike. As a result, there is an urgent need for therapies that are both rapid-acting and safe. This review aims to summarize the prevailing trends in research on novel antidepressants, emphasizing their diversity and multi-directional mechanisms of action. The development of rapid-acting drugs is increasingly focused on achieving high efficacy, particularly for treatment-resistant depression. Such advances offer the potential for rapid therapeutic effects without the prolonged and often tedious administration of older generation antidepressants. Findings from studies using animal models of depression continue to play a crucial role in predicting and designing new therapeutic strategies. These models remain indispensable for understanding the physiological effects of newly developed compounds, thereby guiding the creation of innovative treatments.