Am J Psychiatry 158:1332-1333, August 2001
© 2001 American Psychiatric Association
Classifying Depression
FREDERICK M. QUITKIN, M.D.,
JONATHAN W. STEWART, M.D.,
PATRICK J. MCGRATH, M.D., and
DONALD F. KLEIN, M.D.
New York, N.Y.
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 (3–7), 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 (8–10). 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.
References
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Parker G: Classifying depression: should paradigms lost be regained? Am J Psychiatry 2000; 157:1195-1203
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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
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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[Abstract/Free Full Text]
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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[Abstract/Free Full Text]
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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[Abstract/Free Full Text]
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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[Abstract/Free Full Text]
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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
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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
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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[Abstract/Free Full Text]
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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
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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[CrossRef][Medline]
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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[Abstract/Free Full Text]
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G. PARKER, K. ROY, and D. HADZI-PAVLOVIC
Dr. Parker and Colleagues Reply
Am J Psychiatry,
April 1, 2003;
160(4):
800 - 801.
[Full Text]
[PDF]
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G. Parker, K. Roy, P. Mitchell, K. Wilhelm, G. Malhi, and D. Hadzi-Pavlovic
Atypical Depression: A Reappraisal
Am J Psychiatry,
September 1, 2002;
159(9):
1470 - 1479.
[Abstract]
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