Abstract
Stewart et al (2009) have outlined the evidence in support of the validity of the DSM-IV definition of the ‘With Atypical Features’ episode specifier. Although recognizing the historical significance and clinical utility of the concept of atypical depression, this article takes issue with the DSM-IV criteria. It is concluded that mood reactivity, the A or obligative criterion, is neither significantly associated with the other symptomatic criteria nor useful to diagnose atypical depression, and thus should be eliminated. Problems with operationalization, specification, and reliability of ratings of the diagnostic criteria further limit validity. Despite these limitations in classification, many of the features associated with atypical depression are linked to an early onset of affective illness, including trait-like interpersonal sensitivity, comorbid social anxiety and agoraphobia, a history of childhood physical or sexual trauma, and indicators of the ‘soft’ side of the bipolar spectrum. Neurophysiologic studies also suggest that chronic, early-onset atypical depressions differ from both melancholia and normality. Re-analyses of the Columbia group's seminal studies suggest that preferential response to phenelzine vs imipramine—arguably the strongest validator of atypical depression—similarly appears to be limited to patients with chronic, early-onset syndromes. The criteria for atypical depression need to be revised in DSM-V, including sharpening the operational definitions for the specific symptoms. The importance of age of onset and comorbid anxiety warrant further study. Research examining the validity of a subform of atypical depression characterized by trait-like interpersonal sensitivity and a chronic, early-onset course may further enhance the clinical utility of the DSM-V classification.
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References
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) 4th edn. American Psychiatric Association: Washington, DC.
Angst J, Gamma A, Sellaro R, Zhang H, Merikangas K (2002). Toward validation of atypical depression in the community: results of the Zurich cohort study. J Affect Disord 72: 125–138.
Angst J, Gamma A, Benazzi F, Silverstein B, Ajdacic-Gross V, Eich D et al (2006). Atypical depressive syndromes in varying definitions. Eur Arch Psychiatry Clin Neurosci 256: 44–54.
Anisman H, Ravindran AV, Griffiths J, Merali Z (1994). Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol Psychiatry 4: 182–188.
Bruder GE, Quitkin FM, Stewart JW, Martin C, Voglmaier MM, Harrison WM (1989). Cerebral laterality and depression: differences in perceptual asymmetry among diagnostic subtypes. J Abnorm Psychol 98: 177–186.
Bruder GE, Stewart JW, McGrath PJ, Ma GJ, Wexler BE, Quitkin FM (2002). Atypical depression: enhanced right hemispheric dominance for perceiving emotional chimeric faces. J Abnorm Psychol 111: 446–454.
Davidson JR, Miller RD, Turnbull CD, Sullivan JL (1982). Atypical depression. Arch Gen Psychiatry 39: 527–534.
Fava M, Nierenberg AA, Quitkin FM, Zisook S, Pearlstein T, Stone A et al (1997). A preliminary study on the efficacy of sertraline and imipramine on anger attacks in atypical depression and dysthymia. Psychopharmacol Bull 33: 101–103.
Fotiou F, Fountoulakis KN, Iacovides A, Kaprinis G (2003). Pattern-reversed visual evoked potentials in subtypes of major depression. Psychiatry Res 118: 259–271.
Fries E, Hesse J, Hellhammer J, Hellhammer DH (2005). A new view on hypocortisolism. Psychoneuroendocrinology 30: 1010–1016.
Gillespie RD (1929). The clinical differentiation of types of depression. Guy Hosp Rep 79: 306–344.
Henkel V, Mergl R, Allgaier AK, Kohnen R, Moller JH, Hegerl U (2006). Treatment of depression with atypical features: a meta-analytic approach. Psychiatry Res 141: 89–101.
Henkel V, Mergl R, Coyne JC, Kohnen R, Allgaier AK, Ruhl E et al (2004). Depression with atypical features in a sample of primary care outpatients: prevalence, specific characteristics and consequences. J Affect Disord 83: 237–242.
Himmelhoch JM, Fuchs CZ, Symons BJ (1982). A double-blind study of tranylcypromine treatment of major anergic depression. J Nerv Ment Dis 170: 628–634.
Himmelhoch JM, Thase ME, Mallinger AG, Houck P (1991). Tranylcypromine versus imipramine in anergic bipolar depression. Am J Psychiatry 148: 910–916.
Horwath E, Johnson J, Weissman MM, Hornig CD (1992). The validity of major depression with atypical features based on a community study. J Affect Disord 26: 117–125.
Husain MM, Rush AJ, Sackeim HA, Wisniewski SR, McClintock SM, Craven N et al (2005). Age-related characteristics of depression—a preliminary STAR*D report. Am J Geriatr Psychiatry 13: 852–860.
Joyce PR, Mulder RT, Luty SE, Sullivan PF, McKenzie JM, Abbott RM et al (2002). Patterns and predictors of remission, response and recovery in major depression treated with fluoxetine or nortriptyline. Aus N Z J Psychiatry 36: 384–391.
Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC (1996). The identification and validation of distinct depressive syndromes in a population-based sample of female twins. Arch Gen Psychiatry 53: 391–399.
Klein DF, Davis JM (1969). Diagnosis and Drug Treatment of Psychiatric Disorders. Williams & Wilkins: Baltimore.
Klein DF, Liebowitz MR (1982). Hysteroid dysphoria. Am J Psychiatry 139: 1520–1521.
Korszun A, Moskvina V, Brewster S, Craddock N, Ferrero F, Gill M et al (2004). Familiality of symptom dimensions in depression. Arch Gen Psychiatry 61: 468–474.
Levitan RD, Lesage A, Parikh SV, Goering P, Kennedy SH (1997). Reversed neurovegetative symptoms of depression: a community study of Ontario. Am J Psychiatry 154: 934–940.
Levitan RD, Parikh SV, Lesage AD, Hegadoren KM, Adams M, Kennedy SH et al (1998). Major depression in individuals with a history of childhood physical or sexual abuse: relationship to neurovegetative features, mania, and gender. Am J Psychiatry 155: 1746–1752.
Liebowitz MR, Klein DF (1979). Hysteroid dysphoria. Psychiatr Clin North Am 2: 555–575.
Liebowitz MR, Quitkin FM, Stewart JW, McGrath PJ, Harrison WM, Markowitz JS et al (1988). Antidepressant specificity in atypical depression. Arch Gen Psychiatry 45: 129–137.
Lotufo-Neto F, Trivedi M, Thase ME (1999). Metaanalysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine in the treatment of depression. Neuropsychopharmacology 20: 226–247.
Matza LS, Revicki DA, Davidson JR, Stewart JW (2003). Depression with atypical features in the National Comorbidity Survey: classification, description, and consequences. Arch Gen Psychiatry 60: 817–826.
McGinn LK, Asnis GM, Rubinson E (1996). Biological and clinical validation of atypical depression. Psychiatry Res 60: 191–198.
McGrath PJ, Quitkin FM, Harrison W, Stewart JW (1984). Treatment of melancholia with tranylcypromine. Am J Psychiatry 141: 288–289.
McGrath PJ, Stewart JW, Harrison WM, Ocepek-Welikson K, Rabkin JG, Nunes EN et al (1992). Predictive value of symptoms of atypical depression for differential drug treatment outcome. J Clin Psychopharmacol 3: 197–202.
McGrath PJ, Stewart JW, Harrison W, Wager S, Quitkin FM (1986). Phenelzine treatment of melancholia. J Clin Psychiatry 47: 420–422.
McGrath PJ, Stewart JW, Janal MN, Petkova E, Quitkin FM, Klein DF (2000). A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry 157: 344–350.
McGrath PJ, Stewart JW, Nunes EV, Ocepek-Welikson K, Rabkin JG, Quitkin FM et al (1993). A double-blind crossover trial of imipramine and phenelzine for outpatients with treatment-refractory depression. Am J Psychiatry 150: 118–123.
Newport DJ, Heim C, Bonsall R, Miller AH, Nemeroff CB (2004). Pituitary-adrenal responses to standard and low-dose dexamethasone suppression tests in adult survivors of child abuse. Biol Psychiatry 55: 10–20.
Nierenberg AA, Pava JA, Clancy K, Rosenbaum FJ, Fava M (1996). Are neurovegetative symptoms stable in relapsing or recurrent atypical depressive episodes? Biol Psychiatry 40: 691–696.
Novick JS, Stewart JW, Wisniewski SR, Cook IA, Manev R, Nierenberg AA et al (2005). Clinical and demographic features of atypical depression in outpatients with major depressive disorder: preliminary findings from STAR*D. J Clin Psychiatry 66: 1002–1011.
Pande A, Birkett M, Fechner-Bates S, Haskett R, Greden J (1996). Fluoxetine versus phenelzine in atypical depression. Biol Psychiatry 40: 1017–1020.
Parker G, Parker K, Mitchell P, Wilhelm K (2005). Atypical depression: Australian and US studies in accord. Curr Opin Psychiatry 18: 1–5.
Parker G, Roy K, Mitchell P, Wilhelm K, Malhi G, Hadzi-Pavlovic D (2002). Atypical depression: a reappraisal. Am J Psychiatry 159: 1470–1479.
Pollitt J (1965). The diagnosis and management of depression. Practitioner 194: 597–604.
Posternak MA, Zimmerman M (2001). Symptoms of atypical depression. Psychiatry Res 104: 175–181.
Posternak MA, Zimmerman M (2002). Partial validation of the atypical features subtype of major depressive disorder. Arch Gen Psychiatry 59: 70–76.
Quitkin FM, Harrison W, Stewart JW, McGrath PJ, Tricamo E, Ocepek-Welikson K et al (1991). Response to phenelzine and imipramine in placebo nonresponders with atypical depression. A new application of the crossover design. Arch Gen Psychiatry 48: 319–323.
Quitkin FM, McGrath P, Liebowitz MR, Stewart J, Howard A (1981). Monoamine oxidase inhibitors in bipolar endogenous depressives. J Clin Psychopharmacol 1: 70–74.
Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Wager SG, Nunes E et al (1989). Phenelzine and imipramine in mood reactive depressives. Further delineation of the syndrome of atypical depression. Arch Gen Psychiatry 46: 787–793.
Quitkin F, Rifkin A, Klein DF (1979). Monoamine oxidase inhibitors. A review of antidepressant effectiveness. Arch Gen Psychiatry 36: 749–760.
Quitkin FM, Stewart JW, McGrath PJ, Liebowitz MR, Harrison WM, Tricamo E et al (1988). Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders. Am J Psychiatry 145: 306–311.
Quitkin FM, Stewart JW, McGrath PJ, Tricamo E, Rabkin JG, Ocepek-Welikson K et al (1993). Columbia atypical depression. A subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. Br J Psychiatry 21: 30–34.
Rabkin JR, Stewart JW, Quitkin FM, McGrath PJ, Harrison WM, Klein DF (1996). Should Atypical Depression be Included in DSM -IV?. In: Widiger TA, Frances AJ, Pincus HA, Ross R, First MD, Davis WW (eds). DSM-IV Sourcebook. American Psychiatric Association: Washington, DC. Vol 2, pp 239–260.
Rush AJ, Gullion CM, Basco MR, Jarrett RB, Trivedi MH (1996). The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med 26: 477–486.
Sargant W (1960). Some newer drugs in the treatment of depression and their relation to other somatic treatments. Psychosomatics 1: 14–17.
Sogaard J, Lane R, Latimer P, Behnke K, Christiansen PE, Nielsen B et al (1999). A 12-week study comparing moclobemide and sertraline in the treatment of outpatients with atypical depression. J Psychopharmacol 13: 406–414.
Stewart JW, Bruder GE, McGrath PJ, Quitkin FM (2003). Do age of onset and course of illness define biologically distinct groups within atypical depression? J Abnorm Psychol 112: 253–262.
Stewart JW, McGrath PJ, Quitkin FM (2002). Do age of onset and course of illness predict different treatment outcome among DSM-IV depressive disorders with atypical features? Neuropsychopharmacology 26: 237–245.
Stewart JW, McGrath PJ, Quitkin FM, Klein DF (2009). DSM-IV depression with atypical features: is it valid? Neuropsychopharmacology (E-pub ahead of print 2 September 2009).
Stewart JW, Quitkin FM, McGrath PJ, Klein DF (2005). Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions. J Affect Disord 86: 161–167.
Stewart JW, McGrath PJ, Rabkin JG, Quitkin FM (1993). Atypical depression: a valid clinical entity? Psychiatr Clin North Am 16: 479–495.
Stunkard AJ, Fernstrom MH, Price A, Frank E, Kupfer DJ (1990). Direction of weight change in recurrent depression. Consistency across episodes. Arch Gen Psychiatry 47: 857–860.
Sullivan PF, Prescott CA, Kendler KS (2002). The subtypes of major depression in a twin registry. J Affect Disord 68: 273–284.
Thase ME, Carpenter L, Kupfer DJ, Frank E (1991). Clinical significance of reversed vegetative subtypes of recurrent major depression. Psychopharmacol Bull 27: 17–22.
Thase ME, Mallinger AG, McKnight D, Himmelhoch JM (1992). Treatment of imipramine resistant recurrent depression: IV. A double-blind, crossover study of tranylcypromine in anergic bipolar depression. Am J Psychiatry 149: 195–198.
Thase ME, Trivedi MH, Rush AJ (1995). MAOIs in the contemporary treatment of depression. Neuropsychopharmacology 12: 185–219.
West ED, Dally PJ (1959). Effect of iproniazid in depressive syndromes. Br Med J 1: 1491–1494.
Zisook S, Rush AJ, Albala Z, Alpert J, Balasubramani GK, Fava M et al (2004). Factors that differentiate early vs. later onset of major depression disorder. Psychiatry Res 129: 127–140.
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DISCLOSURE
Dr Thase received no financial support and reports no conflict of interest specifically related to this manuscript. However, as this paper pertains to the assessment and treatment of depression, Dr Thase does disclose the following relationships: during the past 3 years, he has been an advisor or consultant to AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly & Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, MedAvante Inc., Neuronetics Inc., Novartis, Pfizer, Schering-Plough (formerly Organon), Shire US Inc., Supernus Pharmaceuticals, Transcept Pharmaceuticals, and Wyeth Pharmaceuticals. During this time period, he has received grant support from Eli Lilly & Co., GlaxoSmithKline, and Sepracor Inc., as well as the National Institute of Mental Health. During the past 3 years, he has received honoraria for talks sponsored by AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline, Eli Lilly & Co., and Wyeth Pharmaceuticals. He has equity holdings from MedAvante Inc. and has received royalties from American Psychiatric Publishing Inc., Guilford Publications, Herald House, and W.W. Norton & Company Inc. Dr Thase's spouse is an employee of Advogent (Formerly Cardinal Health), who does business with several pharmaceutical companies that manufacture or promote medications approved for the treatment of depression.
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Thase, M. Atypical Depression: Useful Concept, but it's Time to Revise the DSM-IV Criteria. Neuropsychopharmacol 34, 2633–2641 (2009). https://doi.org/10.1038/npp.2009.100
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