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Toward a validation of a new definition of agitated depression as a bipolar mixed state (mixed depression)

Published online by Cambridge University Press:  16 April 2020

F. Benazzi ,
A. Koukopoulos  and
H.S. Akiskal
F. Benazzi*
Affiliation:
Outpatient Psychiatry Center, Via Pozzetto 17, Castiglione di Cervia, 48010 Ravenna, Italy Department of Psychiatry, National Health Service, Forli, Italy
A. Koukopoulos
Affiliation:
Centro Lucio Bini, outpatient private practice, Rome, Italy
H.S. Akiskal
Affiliation:
International Mood Center, University of California, San Diego CA, USA
*
*Corresponding author. E-mail address: [email protected] (F. Benazzi).
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Abstract

Purpose

As psychotic agitated depression is now a well-described form of mixed state during the course of bipolar I disorder, we sought to investigate the diagnostic validity of a new definition for agitated (mixed) depression in bipolar II (BP-II) and major depressive disorder (MDD).

Materials and methods

Three hundred and thirty six consecutive outpatients presenting with major depressive episodes (MDE) but without history of mania were evaluated with the Structured Clinical Interview for DSM-IV when presenting for the treatment of MDE. On the basis of history of hypomania they were assigned to BP-II (n = 206) vs. MDD (n = 130). All patients were also examined for hypomania during the current MDE. Mixed depression was operationally defined by the coexistence of a MDE and at least two of the following excitatory signs and symptoms as described by Koukopoulos and Koukopoulos (Koukopoulos A, Koukopoulos A. Agitated depression as a mixed state and the problem of melancholia. In: Akiskal HS, editor. Bipolarity: beyond classic mania. Psychiatr Clin North Am 1999;22:547–64): inner psychic tension (irritability), psychomotor agitation, and racing/crowded thoughts. The validity of mixed depression was investigated by documenting its association with BP-II disorder and with external variables distinguishing it from unipolar MDD (i.e., younger age at onset, greater recurrence, and family history of bipolar disorders). We analyzed the data with multivariate regression (STATA 7).

Results

MDE plus psychic tension (irritability) and agitation accounted for 15.4%, and MDE plus agitation and crowded thoughts for 15.1%. The highest rate of mixed depression (38.6%) was achieved with a definition combining MDE with psychic tension (irritability) and crowded thoughts: 23.0% of these belonged to MDD and 76.9% to BP-II. Moreover, any of these permutations of signs and symptoms defining mixed depression was significantly and strongly associated with external validators for bipolarity. The mixed irritable-agitated syndrome depression with racing-crowded thoughts was further characterized by distractibility (74–82%) and increased talkativeness (25–42%); of expansive behaviors from the criteria B list for hypomania, only risk taking occurred with some frequency (15–17%).

Conclusions

These findings support the inclusion of outpatient-agitated depressions within the bipolar spectrum. Agitated depression is validated herein as a dysphorically excited form of melancholia, which should tip clinicians to think of such a patient belonging to or arising from a bipolar substrate. Our data support the Kraepelinian position on this matter, but regrettably this is contrary to current ICD-10 and DSM-IV conventions. Cross-sectional symptomatologic hints to bipolarity in this mixed/agitated depressive syndrome are virtually absent in that such patients do not appear to display the typical euphoric/expansive characteristics of hypomania—even though history of such behavior may be elicited by skillful interviewing for BP-II. We submit that the application of this diagnostic entity in outpatient practice would be of considerable clinical value, given the frequency with which these patients are encountered in such practice and the extent to which their misdiagnosis as unipolar MDD could lead to antidepressant monotherapy, thereby aggravating it in the absence of more appropriate treatment with mood stabilizers and/or atypical antipsychotics.

Keywords

Bipolar II disorderUnipolarDepressive mixed stateMixed depressionAgitated depressionExcited melancholia
Type
Original article
Information
European Psychiatry , Volume 19 , Issue 2 , April 2004 , pp. 85 - 90
Copyright
Copyright © 2004 European Psychiatric Association

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References

Akiskal, HSDjenderedjian, AHRosenthal, RHKhani, MKCyclothy-mic disorder: validating criteria for inclusion in the bipolar affective group. Am J Psychiatry 1977;134:1227–33.Google ScholarPubMed
Akiskal, HSWalker, PWPuzantian, VRKing, DRosenthal, TLDranon, MBipolar outcome in the course of depressive illness: phenomenologic, familial, and pharmacologic predictors. J Affect Disord 1983;5:115–28.CrossRefGoogle ScholarPubMed
Akiskal, HSMallya, GCriteria for the “soft” bipolar spectrum: treatment implications. Psychopharmacol Bull 1987;23:68–73.Google ScholarPubMed
Akiskal, HSThe distinctive mixed states of bipolar I, II and III. Clin Neuropharmacol 1992;15(Suppl 1A):S632–3.Google Scholar
Akiskal, HSThe prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. J Clin Psychopharmacol 1996;16(Suppl 1):S4–S14.CrossRefGoogle ScholarPubMed
Akiskal, HSHantouche, EGBourgeois, MLAzorin, JMSechter, DAllilaire, JFet al.Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN). J Affect Disord 1998;50:175–86.CrossRefGoogle Scholar
Akiskal, HSPinto, OThe evolving bipolar spectrum: prototypes I, II, III, and IV. In: Akiskal, HSeditor. Bipolarity: beyond classic mania, 22. 1999. p. 517–34 Psychiatr Clin North Am.Google ScholarPubMed
Akiskal, HSBourgeois, MLAngst, JPost, RMoller, H-JHir-schfeld, RRe-evaluating the prevalence and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000;59(Suppl 1):S5–S30.Google ScholarPubMed
Akiskal, HSBenazzi, FFamily history validation of the bipolar nature of depressive mixed states. J Affect Disord 2003;73:113–22.CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed.Washington (DC): American Psychiatric Association; 1994.Google Scholar
Angst, JThe emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998;50:143–51.Google ScholarPubMed
Benazzi, FPrevalence of bipolar II disorder in outpatient depression: a 203-case study in private practice. J Affect Disord 1997;43:163–6.CrossRefGoogle ScholarPubMed
Benazzi, FAntidepressant-associated hypomania in outpatient depression: a 203-case study in private practice. J Affect Disord 1997;46:73–6.Google ScholarPubMed
Benazzi, FDepressive mixed states: unipolar and bipolar II. Eur Arch Psychiatry Clin Neurosci 2000;250:249–53.CrossRefGoogle ScholarPubMed
Benazzi, FIs 4 days the minimum duration of hypomania in bipolar II disorder? Eur Arch Psychiatry Clin Neurosci 2001;251:32–4.CrossRefGoogle ScholarPubMed
Benazzi, FDepressive mixed state: dimensional versus categorical definitions. Prog Neuropsychopharmacol Biol Psychiatry 2003;27: 129–34.CrossRefGoogle ScholarPubMed
Benazzi, FAkiskal, HSRefining the evaluation of bipolar II: beyond the strict SCID-CV guidelines for hypomania. J Affect Disord 2003; 73:33–8.CrossRefGoogle ScholarPubMed
Cassano, GBAkiskal, HSSavino, MMusetti, LPerugi, GSoriani, AProposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament. J Affect Disord 1992;26:127–40.CrossRefGoogle ScholarPubMed
Coryell, WEndicott, JMaser, JDKeller, MBLeon, ACAkiskal, HSLong-term stability of polarity distinctions in the affective disorders. Am J Psychiatry 1995;152:385–90.Google ScholarPubMed
Dayer, AAubry, J-MRoth, LDucrey, SBertschy, GA theoretical reappraisal of mixed states: dysphoria as a third dimension. Bipolar Disord 2000;2:316–24.CrossRefGoogle ScholarPubMed
Dunner, DLTay, KLDiagnostic reliability of the history of hypoma-nia in bipolar II patients and patients with major depression. Compr Psychiatry 1993;34:303–7.Google ScholarPubMed
First, MBSpitzer, RLGibbon, MWilliams, JBWStructured clinical interview for DSM-IV axis I disorders-clinician version (SCID-CV). Washington (DC): American Psychiatric Press; 1997.Google Scholar
McElroy, SLKeck, PEPope, HGHudson, JIFaedda, GLSwann, ACClinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania. Am J Psychiatry 1992;149:1633–44.Google ScholarPubMed
Ghaemi, SNBoiman, EEGoodwin, FKDiagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry 2000;61:804–8.CrossRefGoogle ScholarPubMed
Goodwin, FKJamison, KRManic-depressive illness. New York: Oxford University Press; 1990.Google Scholar
Hantouche, EGAkiskal, HSLencrenon, SAllilaire, J-FSechter, DAzorin, J-Met al.Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP). J Affect Disord 1998;50:163–7.Google ScholarPubMed
Koukopoulos, AKoukopoulos, AAgitated depression as a mixed state and the problem of melancholia. In: Akiskal, HS editor. Bipolarity: beyond classic mania, 22. 1999. p. 547–64 Psychiatr Clin North Am.Google ScholarPubMed
Kraepelin, EPsychiatrie. 8th ed. Leipzig: JA Barth; 1913.Google Scholar
Perugi, GAkiskal, HSMicheli, CMusetti, LPaianoA, Quilici, Cet al.Clinical subtypes of bipolar mixed states: validating a broader European definition in 143 cases. J Affect Disord 1997;43:169–80.CrossRefGoogle ScholarPubMed
Perugi, GAkiskal, HSMicheli, CToni, CMadaro, DClinical characterization of depressive mixed state in bipolar-I patients: Pisa–San Diego collaboration. J Affect Disord 2001;6:105–14.CrossRefGoogle Scholar
Rihmer, ZPestality, PBipolar II disorder and suicidal behavior. Psychiatr Clin North Am 1999;22:667–73.CrossRefGoogle ScholarPubMed
Robins, EGuze, SBEstablishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiatry 1970; 126:983–7.Google Scholar
Rothman, KJGreenland, SModern epidemiology. 2nd ed.Philadelphia: Lippincott Williams & Wilkins; 1998.Google Scholar
Sato, TBottlender, RSchroter, AMoller, HJFrequency of manic symptoms during a depressive episode and unipolar depressive mixed state as bipolar spectrum. Acta Psychiatr Scand 2003;107:268–74.Google ScholarPubMed
Schatzberg, AFRothschild, AJPsychotic (delusional) major depression. Should it be included as a distinct syndrome in DSM-IV? Am J Psychiatry 1992;149:733–45.Google ScholarPubMed
Swann, ACSecunda, SKKatz, MMCroughan, JBowden, CLKoslow, SHet al.Specificity of mixed affective states: clinical comparison of dysphoric mania and agitated depression. J Affect Disord 1993;28:81–9.CrossRefGoogle ScholarPubMed
Weissman, MMWickramaratne, PAdams, PWolk, SVerdeli, HOlfson, MBrief screening for family psychiatric history. The family history screen. Arch Gen Psychiatry 2000;57:675–82.CrossRefGoogle ScholarPubMed
Williams, JBWTerman, MLink, MJAmira, LRosenthal, NEHypo-mania interview guide (including hyperthymia).Current assessment version (HIGH-C). Norwood, NJ: Clinical Assessment Tools Packet, Center for Environmental Therapeutics; 1994 [rev 2000].Google Scholar
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