0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Classifying Depression
FREDERICK M. QUITKIN, M.D.; JONATHAN W. STEWART, M.D.; PATRICK J. MCGRATH, M.D.; DONALD F. KLEIN, M.D.
Am J Psychiatry 2001;158:1332-a-1333. doi:10.1176/appi.ajp.158.8.1332-a

To the Editor: In his article (1), Gordon Parker, M.D., Ph.D., D.Sc., F.R.A.N.Z.C.P., suggested that the "approach to pursuing potential nonmelancholic subgroupings" is to clinically identify "meaningful syndromes" (p. 1199) with "substantive treatment-specific implications" (p. 1201). We agree with these guidelines, but the failure to include atypical depression as a nonmelancholic subtype is a shortcoming. Atypical depression is included in DSM-IV (296.2) as a parenthetical modifier of major depressive disorder. Atypical depression has been studied in a variety of contexts; a literature review suggests this work fulfills many of Dr. Parker’s criteria and indicates its clinical utility.

Psychopharmacological dissection has been used to identify clinically meaningful subtypes among moderately ill, depressed patients (2). In a series of studies (37), patients with nonautonomous mood disorder received imipramine, phenelzine, or placebo. On the basis of this work, depressive subtypes were identified: a subgroup with atypical depression (overeating and oversleeping) that was characterized by poor response to tricyclic antidepressants (65 of 147, 44%) and good response to monoamine oxidase inhibitors (MAOIs) (118 of 165, 72%) and a second group with simple mood-reactive depression (mild typical) that was characterized by a good response to both tricyclic antidepressants and MAOIs. In both groups, response to placebo was approximately 25%.

By use of items from the Hamilton Depression Rating Scale, a measure of endogeneity (melancholia) was constructed. This analysis implied that melancholic symptoms did not seem to be a precondition for imipramine benefit in this group, which suggests that mild typical depression might differ from severe typical depression (melancholia). Clearly, this distinction is not as well supported as that of atypical depression versus other depressions. The prospective identification of a group with a superior response to MAOIs (versus tricyclic antidepressants) supports a unique pathophysiology and a distinct subtype (8).

A prospective epidemiological study by Kendler et al. (9), using latent class analysis, identified mild typical, atypical, and severe typical depression as categorically distinct subtypes. Subjects with atypical depression were characterized by overeating and oversleeping and a high concordance in monozygotic but not dizygotic twin pairs. The syndrome appeared stable over time. Sullivan et al. (10) independently reproduced this typology and noted, "Particularly interesting…was the identification of depressive classes defined principally by the atypicality of the symptoms."

In another context, the concept of atypical depression helped clarify an obscure outcome in a study contrasting imipramine treatment and two types of psychotherapy (11). The effect of imipramine on subjects with nonatypical depression produced a much brighter signal than psychotherapy when patients with atypical depression were separately analyzed. As anticipated, the response of atypically depressed subjects to imipramine did not surpass their response to placebo.

Although no treatment has been shown equal to that of MAOIs, imipramine, and some second-generation drugs, it is important to identify patients with an atypical depressive subtype (12). Subjects with atypical depression who fail to respond to one or two trials with newer antidepressants should receive a trial with an MAOI. These studies meet Dr. Parker’s concerns and amplify his conclusions. Patient types identified by two distinct approaches, latent class analysis and psychopharmacologic dissection, had strikingly similar phenomenology (810). The use of MAOIs, especially in subjects with atypical depression who have failed to respond to other treatments, is not as widely appreciated as it should be.

Parker G: Classifying depression: should paradigms lost be regained? Am J Psychiatry 2000; 157:1195-  1203
 
Klein DF: The pharmacological validation of diagnoses, in The Validity of Psychiatric Diagnoses. Edited by Robins LN, Barret JE. New York, Raven Press, 1989, pp 203-217
 
Quitkin FM, Stewart JW, McGrath PJ, Liebowitz MR, Harrison WM, Tricamo E, Klein DF, Rabkin JG, Markowitz JS, Wager SG: Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders. Am J Psychiatry  1988; 145:306-311
[PubMed]
 
Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Wager SG, Nunes E, Rabkin JG, Tricamo E, Markowitz J, Klein DF: Phenelzine and imipramine in mood reactive depressives: further delineation of the syndrome of atypical depression. Arch Gen Psychiatry  1989; 46:787-793
[PubMed]
 
Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Tricamo E, Wager SG, Ocepek-Welikson K, Nunes E, Rabkin JG, Klein DF: Atypical depression, panic attacks, and response to imipramine and phenelzine: a replication. Arch Gen Psychiatry  1990; 47:935-941
[PubMed]
 
Quitkin FM, Harrison W, Stewart JW, McGrath PJ, Tricamo E, Ocepek-Welikson K, Rabkin JG, Wager SG, Nunes E, Klein DF: Response to phenelzine and imipramine in placebo nonresponders with atypical depression: a new application of the crossover design. Arch Gen Psychiatry  1991; 48:319-323
[PubMed]
 
Quitkin FM, Stewart JW, McGrath PJ, Tricamo E, Rabkin JG, Ocepek-Welikson K, Nunes E, Harrison W, Klein DF: Columbia atypical depression: a subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. Br J Psychiatry Suppl  1993; 21:30-34
[PubMed]
 
Quitkin FM, Stewart JW, McGrath PJ, Nunes EV, Klein DF: The identification and validation of distinct depressive syndromes in a population-based sample of female twins (letter). Arch Gen Psychiatry  1997; 54:970-972
 
Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC: The identification and validation of distinct depressive syndromes in a population-based sample of female twins. Arch Gen Psychiatry  1996; 53:391-399
[PubMed]
 
Sullivan PF, Kessler RC, Kendler KS: Latent class analysis of lifetime depressive symptoms in the National Comorbidity Survey. Am J Psychiatry 1998; 155:1398-  1406
 
Stewart JW, Garfinkel R, Nunes EV, Donovan S, Klein DF: Atypical features and treatment response in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. J Clin Psychopharmacol  1998; 18:429-434
[PubMed]
[CrossRef]
 
McGrath PJ, Stewart JW, Janal MN, Petkova E, Quitkin FM, Klein DF: A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry  2000; 157:344-350
[PubMed]
[CrossRef]
 
+

References

Parker G: Classifying depression: should paradigms lost be regained? Am J Psychiatry 2000; 157:1195-  1203
 
Klein DF: The pharmacological validation of diagnoses, in The Validity of Psychiatric Diagnoses. Edited by Robins LN, Barret JE. New York, Raven Press, 1989, pp 203-217
 
Quitkin FM, Stewart JW, McGrath PJ, Liebowitz MR, Harrison WM, Tricamo E, Klein DF, Rabkin JG, Markowitz JS, Wager SG: Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders. Am J Psychiatry  1988; 145:306-311
[PubMed]
 
Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Wager SG, Nunes E, Rabkin JG, Tricamo E, Markowitz J, Klein DF: Phenelzine and imipramine in mood reactive depressives: further delineation of the syndrome of atypical depression. Arch Gen Psychiatry  1989; 46:787-793
[PubMed]
 
Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Tricamo E, Wager SG, Ocepek-Welikson K, Nunes E, Rabkin JG, Klein DF: Atypical depression, panic attacks, and response to imipramine and phenelzine: a replication. Arch Gen Psychiatry  1990; 47:935-941
[PubMed]
 
Quitkin FM, Harrison W, Stewart JW, McGrath PJ, Tricamo E, Ocepek-Welikson K, Rabkin JG, Wager SG, Nunes E, Klein DF: Response to phenelzine and imipramine in placebo nonresponders with atypical depression: a new application of the crossover design. Arch Gen Psychiatry  1991; 48:319-323
[PubMed]
 
Quitkin FM, Stewart JW, McGrath PJ, Tricamo E, Rabkin JG, Ocepek-Welikson K, Nunes E, Harrison W, Klein DF: Columbia atypical depression: a subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. Br J Psychiatry Suppl  1993; 21:30-34
[PubMed]
 
Quitkin FM, Stewart JW, McGrath PJ, Nunes EV, Klein DF: The identification and validation of distinct depressive syndromes in a population-based sample of female twins (letter). Arch Gen Psychiatry  1997; 54:970-972
 
Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC: The identification and validation of distinct depressive syndromes in a population-based sample of female twins. Arch Gen Psychiatry  1996; 53:391-399
[PubMed]
 
Sullivan PF, Kessler RC, Kendler KS: Latent class analysis of lifetime depressive symptoms in the National Comorbidity Survey. Am J Psychiatry 1998; 155:1398-  1406
 
Stewart JW, Garfinkel R, Nunes EV, Donovan S, Klein DF: Atypical features and treatment response in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. J Clin Psychopharmacol  1998; 18:429-434
[PubMed]
[CrossRef]
 
McGrath PJ, Stewart JW, Janal MN, Petkova E, Quitkin FM, Klein DF: A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry  2000; 157:344-350
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Books
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 2.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 24.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 12.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 2.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 24.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles