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Activated Depression: Mixed Bipolar Disorder or Agitated Unipolar Depression?

  • Mood Disorders (SM Strakowski, Section Editor)
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Abstract

The combination of depression and activation presents clinical and diagnostic challenges. It can occur, in either bipolar disorder or major depressive disorder, as increased agitation as a dimension of depression. What is called agitation can consist of expressions of painful inner tension or as disinhibited goal-directed behavior and thought. In bipolar disorder, elements of depression can be combined with those of mania. In this case, the agitation, in addition to increased motor activity and painful inner tension, must include symptoms of mania that are related to goal-directed behavior or manic cognition. These diagnostic considerations are important, as activated depression potentially carries increased behavioral risk, especially for suicidal behavior, and optimal treatments for depressive episodes differ between bipolar disorder and major depressive disorder.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. van Praag HM, Asnis GM, Kahn RS, Brown SL, Korn M, Harkavy Friedman JM, et al. Monoamines and abnormal behavior: a multi-aminergic perspective. Br J Psychiatry. 1990;157:723–34.

    Article  PubMed  Google Scholar 

  2. • Johnson SL, Morriss R, Scott J, Paykel E, Kinderman P, Kolamunnage-Dona R, et al. Depressive and manic symptoms are not opposite poles in bipolar disorder. Acta Psychiatr Scand. 2011;123:206–10. A prospective study demonstrating orthogonal and independently varying mania- and depression-related factors in bipolar disorder.

    Article  PubMed  CAS  Google Scholar 

  3. Swann AC, Steinberg JL, Lijffijt M, Moeller GF. Continuum of depressive and manic mixed states in patients with bipolar disorder: quantitative measurement and clinical features. World Psychiatry. 2009;8:166–72.

    PubMed  Google Scholar 

  4. Adler M, Liberg B, Andersson S, Isacsson G, Hetta J. Development and validation of the Affective Self Rating Scale for manic, depressive, and mixed affective states. Nord J Psychiatry. 2008;62:130–5.

    Article  PubMed  Google Scholar 

  5. Meyer TD, Hautzinger M. The structure of affective symptoms in a sample of young adults. Compr Psychiatry. 2003;44:110–16.

    Article  PubMed  Google Scholar 

  6. Carroll BJ. Neurobiologic dimensions in depression and mania. In: Angst J, editor. The origins of depression. Berlin: Springer-Verlag; 1983. p. 163–86.

    Google Scholar 

  7. •• Swann AC, Lafer B, Perugi G, Frye MA, Bauer M, Bahk WM, et al. Bipolar mixed states: an international society for bipolar disorders task force report of symptom structure, course of illness, and diagnosis. Am J Psychiatry. 2013;170:31–42. A comprehensive and critical review of the structure, clinical characteristics, models, and relationship to illness-course of mixed states in bipolar disorder..

    Article  PubMed  Google Scholar 

  8. • Katz MM, Bowden CL, Frazer A. Rethinking depression and the actions of antidepressants: uncovering the links between the neural and behavioral elements. J Affect Disord. 2010;120:16–23. Uses a comprehensive array of clinician, observer, and self-ratings to derive affective symptom factors across unipolar and bipolar disorders..

    Article  PubMed  CAS  Google Scholar 

  9. Ahearn EP, Cassidy F, Kelley L, Weisler RH, Carroll BJ. Dimensions of self-rated mood in depressed, manic, and normal subjects. Compr Psychiatry. 2001;42:196–201.

    Article  PubMed  CAS  Google Scholar 

  10. Gupta RK. Major depression: an illness with objective physical signs. World J Biol Psychiatry. 2009;10:196–201.

    Article  PubMed  Google Scholar 

  11. Koukopoulos A, Sani G, Koukopoulos AE, Manfredi G, Pacchiarotti I, Girardi P. Melancholia agitata and mixed depression. Acta Psychiatr Scand Suppl. 2007;433:50–7.

    Article  PubMed  Google Scholar 

  12. Spitzer RL, Endicott J, Robins E. Research diagnostic criteria for a selected group of functional disorders. 3rd ed. New York: New York State Psychiatric Institute Biometrics Inst; 1978.

    Google Scholar 

  13. Basso M, Combs D, Purdie R, Candilis P, Bornstein R. Neuropsychological correlates of symptom dimensions in inpatients with major depressive disorder. Psychiatry Res. 2013;207:61–7.

    Article  PubMed  Google Scholar 

  14. Akiskal HS, Benazzi F, Perugi G, Rihmer Z. Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy. J Affect Disord. 2005;85:245–58.

    Article  PubMed  Google Scholar 

  15. Benazzi F. Agitated depression: a valid depression subtype? Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:1279–85.

    Article  PubMed  Google Scholar 

  16. Benazzi F. Agitated depression in bipolar II disorder. World J Biol Psychiatry. 2005;6:198–205.

    Article  PubMed  Google Scholar 

  17. Maj M, Pirozzi R, Magliano L, Fiorillo A, Bartoli L. Agitated “unipolar” major depression: prevalence, phenomenology, and outcome. J Clin Psychiatry. 2006;67:712–19.

    Article  PubMed  Google Scholar 

  18. Olgiati P, Serretti A, Colombo C. Retrospective analysis of psychomotor agitation, hypomanic symptoms, and suicidal ideation in unipolar depression. Depress Anxiety. 2006;23:389–97.

    Article  PubMed  Google Scholar 

  19. Parker G, Hadzi-Pavlovic D, Brodaty H, Boyce P, Mitchell P, Wilhelm K, et al. Psychomotor disturbance in depression: defining the constructs. J Affect Disord. 1993;27:255–65.

    Article  PubMed  CAS  Google Scholar 

  20. Katz MM, Secunda SK, Koslow SH, Maas JW, Berman N, Casper R, et al. A multivantaged approach to measurement of behavioral and affect states for clinical and psychobiological research. Psychol Rep. 1984;55:619–71.

    Article  PubMed  CAS  Google Scholar 

  21. Angst J, Gamma A, Benazzi F, Ajdacic V, Rossler W. Does psychomotor agitation in major depressive episodes indicate bipolarity? Evidence from the Zurich Study. Eur Arch Psychiatry Clin Neurosci. 2009;259:55–63.

    Article  PubMed  Google Scholar 

  22. Swann AC, Secunda SK, Katz MM, Croughan J, Bowden CL, Koslow SH, et al. Specificity of mixed affective states: clinical comparison of dysphoric mania and agitated depression. J Affect Disord. 1993;28:81–9.

    Article  PubMed  CAS  Google Scholar 

  23. Wolff EAI, Putnam FW, Post RM. Motor activity and affective illness: the relationship of amplitude and temporal distribution to changes in affective state. Arch Gen Psychiatry. 1985;42:288–94.

    Article  PubMed  Google Scholar 

  24. • Razavi N, Horn H, Koschorke P, Hugli S, Hofle O, Muller T, et al. Measuring motor activity in major depression: the association between the Hamilton Depression Rating Scale and actigraphy. Psychiatry Res. 2011;190:212–16. Differentiated depressive agitation from goal-directed activity using actigraphy—one of the few studies to directly use actigraphy to study this question..

    Article  PubMed  Google Scholar 

  25. Kraepelin E. Manic-depressive insanity and paranoia. In: Robertson GM, Barclay RBT, editors. XXX. Edinburgh: E & S Livingstone; 1921.

  26. Akiskal HS, Benazzi F. Validating Kraepelin’s two types of depressive mixed states: “depression with flight of ideas” and “excited depression”. World J Biol Psychiatry. 2004;5:107–13.

    Article  PubMed  Google Scholar 

  27. Benazzi F. Depression with racing thoughts. Psychiatry Res. 2003;120:273–82.

    Article  PubMed  Google Scholar 

  28. Benazzi F. Unipolar depression with racing thoughts: a bipolar spectrum disorder? Psychiatry Clin Neurosci. 2005;59:570–5.

    Article  PubMed  Google Scholar 

  29. Perugi G, Akiskal HS, Micheli C, Toni C, Madaro D. Clinical characterization of depressive mixed state in bipolar-I patients: Pisa-San Diego collaboration. J Affect Disord. 2001;67:105–14.

    Article  PubMed  CAS  Google Scholar 

  30. Mitchell P, Parker G, Jamieson K, Wilhelm K, Hickie I, Brodaty H, et al. Are there any differences between bipolar and unipolar melancholia? J Affect Disord. 1992;25:97–105.

    Article  PubMed  CAS  Google Scholar 

  31. Rybakowski JK, Suwalska A, Lojko D, Rymaszewska J, Kiejna A. Types of depression more frequent in bipolar than in unipolar affective illness: results of the Polish DEP-BI study. Psychopathology. 2007;40:153–8.

    Article  PubMed  Google Scholar 

  32. Benazzi F. Bipolar family history of the hypomanic symptoms and dimensions of mixed depression. Compr Psychiatry. 2005;46:399–404.

    Article  PubMed  Google Scholar 

  33. Benazzi F. Is depressive mixed state a transition between depression and hypomania? Eur Arch Psychiatry Clin Neurosci. 2004;254:69–75.

    Article  PubMed  Google Scholar 

  34. Katz MM, Robins E, Croughan J, Secunda S, Swann A. Behavioral measurement and drug response characteristics of unipolar and bipolar depression. Psychol Med. 1982;12:25–36.

    Article  PubMed  CAS  Google Scholar 

  35. •• Fiedorowicz JG, Endicott J, Leon AC, Solomon DA, Keller MB, Coryell WH. Subthreshold hypomanic symptoms in progression from unipolar major depression to bipolar disorder. Am J Psychiatry. 2011;168:40–8. Demonstrates the relationship between initial occurrence of hypomanic symptoms limited to depressive episodes and eventual occurrence of free-standing mania or hypomania. The strong implication is that manic symptoms limited to depressive episodes are evidence for bipolar disorder..

    Article  PubMed  Google Scholar 

  36. Judd LL, Schettler PJ, Akiskal H, Coryell W, Fawcett J, Fiedorowicz JG, et al. Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes. J Affect Disord. 2012;138:440–8.

    Article  PubMed  Google Scholar 

  37. Swann AC, Moeller FG, Steinberg JL, Schneider L, Barratt ES, Dougherty DM. Manic symptoms and impulsivity during bipolar depressive episodes. Bipolar Disord. 2007;9:206–12.

    Article  PubMed  Google Scholar 

  38. Swann AC, Geller B, Post RM, Altshuler L, Chang KD, DelBello MP, et al. Practical clues to early recognition of bipolar disorder: a primary care approach. Prim Care Companion J Clin Psychiatry. 2005;7:15–21.

    Article  PubMed  Google Scholar 

  39. Rihmer A, Gonda X, Balazs J, Faludi G. The importance of depressive mixed states in suicidal behaviour. Neuropsychopharmacol Hung. 2008;10:45–9.

    PubMed  Google Scholar 

  40. Benazzi F. Classifying mood disorders by age-at-onset instead of polarity. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:86–93.

    Article  PubMed  Google Scholar 

  41. • Perugi G, Toni C, Maremmani I, Tusini G, Ramacciotti S, Madia A, et al. The influence of affective temperaments and psychopathological traits on the definition of bipolar disorder subtypes: A study on Bipolar I Italian National sample. J Affect Disord. 2010;136:e41–9. In a large, well-studied clinical population, these authors demonstrate relationships between illness-course characteristics and episode properties..

    Article  PubMed  Google Scholar 

  42. Benazzi F. A continuity between bipolar II depression and major depressive disorder? Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1043–50.

    Article  PubMed  Google Scholar 

  43. • Cassano GB, Rucci P, Benvenuti A, Miniati M, Calugi S, Maggi L, et al. The role of psychomotor activation in discriminating unipolar from bipolar disorders: a classification-tree analysis. J Clin Psychiatry. 2012;73:22–8. Systematically explores differential diagnostic relationships involving motor and internal activation..

    Article  PubMed  Google Scholar 

  44. Benazzi F. Reviewing the diagnostic validity and utility of mixed depression (depressive mixed states). Eur Psychiatry. 2008;23:40–8.

    Article  PubMed  Google Scholar 

  45. • Mazza M, Mandelli L, Zaninotto L, Nicola MD, Martinotti G, Harnic D, et al. Factors associated with the course of symptoms in bipolar disorder during a 1-year follow-up: depression vs. sub-threshold mixed state. Nord J Psychiatry. 2011;65:419–26. Longitudinal study demonstrating the extent to which diagnostically important mixed symptoms are missed in bipolar disorder..

    Article  PubMed  Google Scholar 

  46. Biondi M, Picardi A, Pasquini M, Gaetano P, Pancheri P. Dimensional psychopathology of depression: detection of an ‘activation’ dimension in unipolar depressed outpatients. J Affect Disord. 2005;84:133–9.

    Article  PubMed  CAS  Google Scholar 

  47. Bertschy G, Gervasoni N, Favre S, Liberek C, Ragama-Pardos E, Aubry JM, et al. Frequency of dysphoria and mixed states. Psychopathology. 2008;41:187–93.

    Article  PubMed  CAS  Google Scholar 

  48. Henry C, M’Bailara K, Poinsot R, Casteret AA, Sorbara F, Leboyer M, et al. Evidence for two types of bipolar depression using a dimensional approach. Psychother Psychosom. 2007;76:325–31.

    Article  PubMed  Google Scholar 

  49. Goldberg JF, Perlis RH, Ghaemi SN, Calabrese JR, Bowden CL, Wisniewski S, et al. Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: Findings From the STEP-BD. Am J Psychiatry. 2007;164:1348–55.

    Article  PubMed  Google Scholar 

  50. • Baldessarini RJ, Faedda GL, Offidani E, Vazquez GH, Marangoni C, Serra G, et al. Antidepressant-associated mood-switching and transition from unipolar major depression to bipolar disorder: a review. J Affect Disord. 2013;148:129–35. Incidence of antidepressant-associated affective and diagnostic change in a large clinical population..

    Article  PubMed  CAS  Google Scholar 

  51. Stokes PE, Stoll PM, Koslow SH, Maas JW, Davis JM, Swann AC, et al. Pretreatment DST and hypothalamic-pituitary-adrenocortical function in depressed patients and comparison groups. Arch Gen Psychiatry. 1984;41:257–67.

    Article  PubMed  CAS  Google Scholar 

  52. Kocsis JH, Davis JM, Katz MM, Koslow SH, Stokes PE, Casper R, et al. Depressive behavior and hyperactive adrenocortical function. Am J Psychiatry. 1985;142:1291–8.

    PubMed  CAS  Google Scholar 

  53. Maas JW, Katz MM, Koslow SH, Swann AC, Davis JM, Berman N, et al. Adrenomedullary function in depressed patients. J Psychiatric Res. 1994;28:357–67.

    Article  CAS  Google Scholar 

  54. Swann AC, Secunda SK, Koslow SH, Katz MM, Bowden CL, Maas JW, et al. Mania: sympathoadrenal function and clinical state. Psychiatry Res. 1991;37:195–205.

    Article  PubMed  CAS  Google Scholar 

  55. Swann AC, Katz MM, Bowden CL, Berman NG, Stokes PE. Psychomotor performance and monoamine function in bipolar and unipolar affective disorders. Biol Psychiatry. 1999;45:979–88.

    Article  PubMed  CAS  Google Scholar 

  56. Swann AC, Koslow SH, Katz MM, Maas JW, Javaid J, Secunda SK, et al. Lithium carbonate treatment of mania. Cerebrospinal fluid and urinary monoamine metabolites and treatment outcome. Arch Gen Psychiatry. 1987;44:345–54.

    Article  PubMed  CAS  Google Scholar 

  57. Swann AC, Stokes PE, Casper R, Secunda SK, Bowden CL, Berman N, et al. Hypothalamic-pituitary-adrenocortical function in mixed and pure mania. Acta Psychiatr Scand. 1992;85:270–4.

    Article  PubMed  CAS  Google Scholar 

  58. Swann AC, Stokes PE, Secunda S, Maas JW, Bowden CL, Berman N, et al. Depressive mania vs agitated depression: biogenic amine and hypothalamic-pituitary-adrenocortical function. Biol Psychiatry. 1994;35:803–13.

    Article  PubMed  CAS  Google Scholar 

  59. Bunney Jr WE, Goodwin FK, House KM, Gordon EK. The “switch process” in manic-depressive illness: II. Relationship to catecholamines, REM sleep, and drugs. Arch Gen Psychiatry. 1972;27:304–9.

    Article  PubMed  Google Scholar 

  60. Post RM, Stoddard FJ, Gillin JC. Alterations in motor activity, sleep, and biochemistry in a cycling manic-depressive patient. Arch Gen Psychiatry. 1977;34:470–7.

    Article  PubMed  CAS  Google Scholar 

  61. Henna E, Hatch JP, Nicoletti M, Swann AC, Zunta-Soares G, Soares JC. Is impulsivity a common trait in bipolar and unipolar disorders? Bipolar Disord. 2013;15:223–7.

    Article  PubMed  Google Scholar 

  62. Del Carlo A, Benvenuti M, Fornaro M, Toni C, Rizzato S, Swann AC, et al. Different measures of impulsivity in patients with anxiety disorders: a case control study. Psychiatry Res. 2012;197:231–6.

    Article  PubMed  Google Scholar 

  63. Bellani M, Hatch JP, Nicoletti MA, Ertola AE, Zunta-Soares G, Swann AC, et al. Does anxiety increase impulsivity in patients with bipolar disorder or major depressive disorder? J Psychiatr Res. 2012;46:616–21.

    Article  PubMed  Google Scholar 

  64. Balazs J, Benazzi F, Rihmer Z, Rihmer A, Akiskal KK, Akiskal HS. The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention. J Affect Disord. 2006;91:133–8.

    Article  PubMed  Google Scholar 

  65. Simon TR, Swann AC, Powell KE, Potter LB, Kresnow M, O’Carroll PW. Characteristics of impulsive suicide attempts and attempters. Suicide Life Threat Behav. 2001;32 Suppl 1:49–59.

    Article  PubMed  CAS  Google Scholar 

  66. •• Sani G, Tondo L, Koukopoulos A, Reginaldi D, Kotzalidis GD, Koukopoulos AE, et al. Suicide in a large population of former psychiatric inpatients. Psychiatry Clin Neurosci. 2011;65:286–95. Properties of completed suicide relative to diagnostic and clinical factors in a large population over an extended period..

    Article  PubMed  Google Scholar 

  67. Goldberg JF, Perlis RH, Bowden CL, Thase ME, Miklowitz DJ, Marangell LB, et al. Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2009;166:173–81.

    Article  PubMed  Google Scholar 

  68. Dilsaver SC, Swann AC. Mixed mania: apparent induction by a tricyclic antidepressant in five consecutively treated patients with bipolar depression. Biol Psychiatry. 1995;37:60–2.

    Article  PubMed  CAS  Google Scholar 

  69. Akiskal HS, Benazzi F, Perugi G, Rihmer Z. Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy. J Affect Disord. 2005;85:245–58.

    Article  PubMed  Google Scholar 

  70. Swann AC, Dougherty DM, Pazzaglia PJ, Pham M, Steinberg JL, Moeller FG. Increased impulsivity associated with severity of suicide attempt history in patients with bipolar disorder. Am J Psychiatry. 2005;162:1680–7.

    Article  PubMed  Google Scholar 

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Alan C. Swann declares that he has no conflict of interest.

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  1. Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Road, Room 3216, Houston, TX, 77054, USA

    Alan C. Swann

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Swann, A.C. Activated Depression: Mixed Bipolar Disorder or Agitated Unipolar Depression?. Curr Psychiatry Rep 15, 376 (2013). https://doi.org/10.1007/s11920-013-0376-1

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