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Atypical Depression

A Comprehensive Review

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Abstract

Despite several decades of research, the characteristics distinguishing atypical depression from other depressive subtypes remain ambiguous. Multiple lines of evidence support the designation of atypical depression as a scientifically and clinically relevant subtype, including differences in hormonal responses, brain laterality, psychological profile and psychiatric co-morbidity and differential treatment response. The evolution of the diagnostic criteria for atypical depression has led to the designation of mood reactivity as the cardinal feature, and the research supporting this conclusion is reviewed.

This paper also reviews the evidence for the drug treatment of atypical depression, with a particular focus on research related to the superior efficacy of monoamine oxidase inhibitors (MAOIs) compared with tri cyclic anti-depressants (TCAs). Data relevant to the efficacy of newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline (norepinephrine) reuptake inhibitors, transdermal selegiline and other new agents for atypical depression, are discussed.

In summary, the diagnostic reliability and validity of atypical depression still remain elusive and open to further evolution. Currently available findings suggest that atypical depression has preferential response to MAOIs over TCAs. More data are required to determine the efficacy of newer agents relative to MAOIs and TCAs, although limited studies have shown a noninferior efficacy and better tolerability of newer agents such as SSRIs compared with those of MAOIs and TCAs. Finally, future directions for research include further refinement of the diagnostic criteria for atypical depression, and clarification of the role of newer antidepressants in the treatment of this subtype with evidence from randomized, controlled trials.

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Acknowledgements

This research was supported by a grant from the Medical Research Center, Korea Science and Engineering Foundation, Republic of Korea (R13-2002-005-04001-0).

Dr Pae has received research grants from GlaxoSmithKline Korea, AstraZeneca Korea, Janssen Pharmaceutica Korea, Eli Lilly and Company Korea, Korean Research Foundation, Otsuka Korea, Wyeth Korea, and the Korean Institute of Science and Technology Evaluation and Planning. He has received honoraria and is on the speakers’ bureaus of GlaxoSmithKline Korea, Lundbeck Korea, AstraZeneca Korea, Janssen Pharmaceutica Korea, Eli Lilly and Company Korea, McNeil Consumer and Specialty Inc. and Otsuka Korea.

Dr Marks is a consultant for Bristol-Myers Squibb and is on the speakers’ bureaus of Eli Lilly and Company and Pfizer Inc. He has received research support from Merck and Johnson & Johnson.

Dr Patkar is a consultant for Bristol-Myers Squibb, GlaxoSmithKline and Reckitt Benckiser. He is on the speakers’ bureaus and has received honoraria from Bristol-Myers Squibb, Cephalon, Pfizer Inc. and Reckitt Benckiser. He has received grant support from the National Institutes of Health, AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen Pharmaceutica, Jazz Pharmaceuticals, Lundbeck, McNeil Consumer & Specialty Inc., Organon and Pfizer Inc.

Dr Masand is a consultant for Bristol-Myers Squibb, Eli Lilly and Company, i3 CME, Janssen Pharmaceutica, Organon and Pfizer Inc. He is on the speakers’ bureaus of Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc. and Eli Lilly and Company.

Dr Tharwani has no conflicts of interest that are directly relevant to the content of this review.

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Pae, CU., Tharwani, H., Marks, D.M. et al. Atypical Depression. CNS Drugs 23, 1023–1037 (2009). https://doi.org/10.2165/11310990-000000000-00000

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