There are a variety of barriers to major depressive disorder (MDD) treatment which may impede access to professional help and prevent best patient outcome. These barriers include the heterogeneity of MDD, societal factors, and clinician-patient relationship as well as issues of concordance, compliance, and adherence.

Efficacy, safety, and tolerability are primary parameters for evaluation of any pharmacologic treatment. However, in order to evaluate the effectiveness of a new treatment in everyday clinical practice, these parameters must be assessed in the context of a number of societal, patient, and methodological variables.

Data from a variety of studies, including the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, have shown that fewer patients achieve remission from symptoms of major depressive disorder (MDD) and other depressive disorders after taking the first-prescribed antidepressant treatment than was expected. The goal of treatment is true remission: the complete absence of symptoms. Achieveing less than true remission is associated with MDD recurrence and continued impairment.

Review of extant biological data would suggest that major depressive disorder (MDD) is a term used to subsume a syndrome that may involve a variety of different pathophysiological processes. Current research has implicated a myriad of different factors in the pathogenesis of depressive disorders including: genetic predisposition, “hormonal” abnormalities, disturbances in neurostransmitters, disturbances in neurocircuitry, and immune dysfunction. Our most recent consensus suggests that the depressive disorders reflect the interplay between these biological systems and psychosocial experiences, such as early-life trauma and current life stressors. Thus, MDD truly represents a complex heterogeneous syndrome. This conceptualization suggests that a variety of different types of treatment approaches will be necessary to adequately ameliorate the symptoms of patients suffering from this syndrome. Although this is a daunting task, we are beginning to develop approaches that will enable us to add to our armamentation of biological treatments.