Difficult-to-Treat Depressions: A Primary Care Perspective

Depression is common in primary care and more difficult to treat than many clinicians are aware. The goal of treatment is symptomatic remission, and by current estimates 50% or more of patients treated with antidepressant monotherapy may suffer from residual neurovegetative, cognitive, and somatic symptoms. Bipolar disorder, in particular, is more prevalent in primary care than previously recognized, is easily misdiagnosed, and may be a significant source of treatment failure. This article reviews treatment resistance, its causes, and management approaches. Many strategies are straightforward and within the skill set of primary care clinicians. The use of antidepressants with multiple mechanisms of action may reduce first-order resistance. Antidepressant augmentation strategies (e.g., with lithium or atypical antipsychotics) are often very effective and readily instituted by informed and motivated practitioners.