The burden of disease for treatment-resistant depression

Assessing the consequences of specific diseases on global, national, and in dividual levels is complex. The Global Burden of Disease Study was launched in 1992 to develop objective measures of the burden of disease. Two measur es have become widely accepted: disability-adjusted life-years (DALYs) asse sses years of life lost due to a disease plus years lived with the disabili ty due to that disease, and years lived with disability (YLDs) is a related measure with greater relevance for diseases that do not routinely produce earlier mortality. When DALYs and YLDs were compared worldwide for 100 diso rders, they revealed a huge burden of disease for depression. Indeed, the f indings were startling. Neuropsychiatric conditions are by far the world's leader in YLDs, accounting for almost 30%. Unipolar major depressive disord er alone accounted for 11% of global YLDs. The disability of major depressi ve disorder produces its greatest burden upon women and starts early in lif e. No separate disability assessments have been compiled for treatment-resi stant depression, but of individuals with major depressive disorder, the mo st severely disabled are those with treat ment-resistant depression. The co ntributions to the morbidity associated with major depressive disorder and treatment-resistant depression include widespread prevalence; relatively ea rly symptom onsets severe underdiagnosis and undertreatment; genetic vulner abilities and precipitation or accentuation by relatively unavoidable stres sors; a longitudinal pattern of frequent recurrences with increasing freque ncy, severity, and consequences unless treated with maintenance strategies; inadequate prioritization of recurrence prevention among clinicians; and p ossible suppression of brain neurogenesis, neuronal atrophy, cell death, hi ppocampal dysfunction, and magnetic resonance imaging changes for those wit h chronic treatment-resistant depression. Since the patterns of recurrences , cycle acceleration, and increasing severity of treatment-resistant depres sion are key reasons for its high burden, reducing the burden requires an e ntire paradigm shift, including emphasis on the prevention of recurrences. Only then will this prevalent, disabling yet treatable disorder lose its ig nominious status as a world leader in disease burden.