Identifying difficult-to-treat depression: differential diagnosis, subtypes, and comorbidities.

Treatment-resistant depression (TRD) is a common clinical presentation responsible for much of the burden of major depressive disorder worldwide. For this reason, TRD requires aggressive identification and management. Although several models have been proposed to describe TRD, consensus is still needed on the criteria (ie, dose, duration, compliance, number of trials required) used to define treatment response and resistance. When diagnosing patients with depression, clinicians should identify risk factors associated with treatment resistance, including clinical subtypes of depression and medical or psychiatric comorbidities that could affect the course of treatment. When evaluating a patient who has not responded to a first course of antidepressant treatment, the clinician should verify the primary diagnosis and ensure that the patient has adhered to a treatment regimen that was of adequate dose and duration.