Beyond the Umbrella Term: Rethinking Major Depressive Disorder

Ron Pies, MD, traced the evolution of antidepressant treatment across his career, from the tricyclic antidepressants and monoamine oxidase inhibitors used during his residency training in the late 1970s and 1980s to the selective serotonin reuptake inhibitors (SSRIs) that later dominated practice and, more recently, serotonin-norepinephrine reuptake inhibitors and multimodal agents such as vortioxetine. Pies noted that vortioxetine, studied extensively by Roger McIntyre, MD, demonstrated a better side effect profile than classic SSRIs in many respects.¹ He characterized the trajectory as evolutionary rather than revolutionary—current antidepressants are effective for many patients and their side effects can usually be managed, but no agent works for everybody. Pies also pointed to newer somatic approaches, including esketamine, as part of this shift, describing the overall change in major depressive disorder treatment as meaningful but incremental rather than transformative.

"I think I'd want clinicians to remember that depression is an umbrella term that really doesn't tell you very much," Pies said, comparing the label to a mechanic's vague diagnosis of "engine trouble."

Pies argued that differential diagnosis should be the starting point whenever a patient presents with depression, since major depressive disorder is a highly heterogeneous condition rather than a single entity. He noted that Diagnostic and Statistical Manual of Mental Disorders criteria for a major depressive episode are broad and, in his view, not a particularly valid construct—an observation consistent with empirical findings that more than 200 unique symptom combinations can qualify for the same diagnosis.²

Immediate, emergent considerations also factor into evaluation, Pies said: "Does the person have suicidal ideation? Is there a psychotic component to the depression? Is it a melancholic depression?" He added that clinicians should assess whether substance use is contributing to the depressive presentation and whether hospitalization is warranted, noting that each of these factors carries direct treatment implications. Rather than settling for a generic view of major depressive disorder, Pies said, clinicians need to treat it as the heterogeneous condition it is.

Dr Pies is editor-in-chief emeritus of Psychiatric Times and professor emeritus of psychiatry at SUNY Upstate Medical University.

References

1. McIntyre RS, Florea I, Tonnoir B, et al. Efficacy of vortioxetine on cognitive functioning in working patients with major depressive disorder. J Clin Psychiatry. 2017;78(1):115-121.

2. Fried EI, Nesse RM. Depression is not a consistent syndrome: an investigation of unique symptom patterns in the STAR*D study. J Affect Disord. 2014;172:96-102.