Major Depressive Disorder (MDD) is a major cause of morbidity worldwide. Lifetime prevalence varies widely by country, and is estimated around 17% in the United States. MDD is currently the leading cause of disease burden in North America and other high-income countries, and is the fourth-leading cause of disease burden worldwide. According to the World Health Organization, by the year 2030, MDD is predicted to become the secondleading cause of disease burden worldwide after HIV. MDD is usually recurrent and national practice guidelines recommend maintenance pharmacotherapy for most patients with a history of major depressive episodes, owing to their favorable risk/benefit ratio. Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly endorsed as a first line treatment for MDD. Indeed, SSRI have enjoyed wide popularity as a result of their selective pharmacology and the consequently better tolerability and lesser toxicity than the first-generation antidepressants. However, a high percentage of patients fail to achieve complete remission when treated with a SSRI.
Among the symptoms that fail to improve are often included fatigue, low energy and loss of interests, i.e. those symptoms that may be associated with dopaminergic and noradrenergic systems dysfunction. Such symptoms may respond to medications with a noradrenergic and/ or dopaminergic component to their pharmacology, such as bupropion and duloxetine.
This paper briefly reviews and comments on the heterogeneity of depression, on the pharmacodynamics differences among the various available antidepressants and on the need to personalize the treatment of depression based on the symptom presentation.