Depression unveiled: a comprehensive review of pathophysiology and treatment advances

Depression is one of the most commonly diagnosed mental health disorders among adults and is currently the third leading cause of disease worldwide. Depression, also referred to as major depressive disorder (MDD), poses a significant global health challenge, affecting over 300 million individuals worldwide. In sub-Saharan Africa, neuropsychiatric conditions account for nearly 10% of the disease burden, with depression being the most frequently diagnosed disorder. Clinically, depression manifests through symptoms such as feelings of worthlessness, cognitive and sleep disturbances, and suicidal ideation, with major depression representing the predominant subtype. Its complex pathogenesis has been extensively investigated, incorporating hypotheses related to genetic predisposition, neurotransmitter dysregulation, and hypothalamic-pituitary-adrenal (HPA) dysfunction, among others. While both pharmacological and non-pharmacological interventions demonstrate efficacy, antidepressant medications remain the cornerstone of treatment. Untreated depression can lead to widespread emotional, behavioural, and physical health complications, significantly impairing quality of life. This review reports current hypotheses regarding the underlying pathophysiology of depression and evaluates therapeutic strategies with an emphasis on the pharmacological profile of the classes used to treat depression.