Atypical Depression in the 21st Century: Diagnostic and Treatment Issues

Author(s)Mario A. Cristancho, MD, John P. O’reardon, MD, Michael E. Thase, MD

Identification of atypical features is important in the treatment of depression for both treatment selection and prognosis, especially when initial measures prove ineffective. The concept of atypical depression has evolved over many years, and now it appears timely for a further revision.

[Editor's Note: Originally presented as an independent educational activity under the direction of CME LLC, this article was published by Psychiatric Times (2011;28[1]:42-47). The ability to receive CME credits has expired. The article is presented here for informational purposes.]

The existence of different subtypes of depressive episodes (ie, endogenous and nonendogenous) was initially postulated at least 80 years ago.^1,2 In the early formulations, the term “endogenous depression” was used to describe a more severe biologically mediated illness, whereas “nonendogenous depression” or “exogenous depression” referred to a less severe and environmentally mediated condition characterized by mood reactivity.³ It was not until the introduction of the first monoamine oxidase inhibitor (MAOI)-iproniazid-that the term “atypical depression” began to emerge to describe a particular variant of nonendogenous depression.

Originally, endogenous, or melancholic, depression was thought to be the prototypical form of depression.⁴ Endogenous depression manifested with neurovegetative symptoms and nonreactive mood and regularly responded to the tricyclic antidepressant (TCA) imipramine and/or electroconvulsive therapy (ECT). A different subgroup of patients was found to be responsive to iproniazid (the first commercially available MAOI, but currently off the market because of significant toxicity) and nonresponsive to well-established treatments for depression (ie, imipramine and ECT).⁵ Furthermore, those patients presented an unusual constellation of symptoms characterized by the absence of endogenous-type neurovegetative symptoms and the presence of emotional reactivity.⁴

On the basis of these early observations, the existence of a unique subtype of nonendogenous depressive episodes characterized by mood reactivity with reversed neurovegetative symptoms (ie, hypersomnia and hyperphagia) and a predictable response to certain antidepressants was proposed and termed “atypical depression.” The hypothesis that such depressions were relatively nonresponsive to TCAs and more responsive to MAOIs was further supported by studies in the 1970s and 1980s.^6-9 Atypical depression was formally recognized in 1994, when it was included as an “episode specifier” in DSM-IV.¹⁰

DIAGNOSIS

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