Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-18T10:02:48.424Z Has data issue: false hasContentIssue false
  • English
  • Français

Mixed features in major depressive disorder: diagnoses and treatments

Published online by Cambridge University Press:  02 May 2017

Trisha Suppes  and
Michael Ostacher
Trisha Suppes*
Affiliation:
VA Palo Alto Health Care System, Palo Alto, California, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA
Michael Ostacher
Affiliation:
VA Palo Alto Health Care System, Palo Alto, California, USA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA
*
*Address for correspondence: Trisha Suppes, MD, PhD, VA Palo Alto Health Care System, 3801 Miranda Ave. 151T, Palo Alto, CA 94304, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

For the first time in 20 years, the American Psychiatric Association (APA) updated the psychiatric diagnostic system for mood disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Perhaps one of the most notable changes in the DSM-5 was the recognition of the possibility of mixed symptoms in major depression and related disorders (MDD). While MDD and bipolar and related disorders are now represented by 2 distinct chapters, the addition of a mixed features specifier to MDD represents a structural bridge between bipolar and major depression disorders, and formally recognizes the possibility of a mix of hypomania and depressive symptoms in someone who has never experienced discrete episodes of hypomania or mania. This article reviews historical perspectives on “mixed states” and the recent literature, which proposes a range of approaches to understanding “mixity.” We discuss which symptoms were considered for inclusion in the mixed features specifier and which symptoms were excluded. The assumption that mixed symptoms in MDD necessarily predict a future bipolar course in patients with MDD is reviewed. Treatment for patients in a MDD episode with mixed features is critically considered, as are suggestions for future study. Finally, the premise that mood disorders are necessarily a spectrum or a gradient of severity progressing in a linear manner is argued.

Keywords

Atypical antipsychoticsdiagnosismajor depressionmixed featuresmixed symptomsmood disorderstreatment
Type
Review Articles
Information
CNS Spectrums , Volume 22 , Issue 2: Theme: Mixed features in major depressive episodes , April 2017 , pp. 155 - 160
Copyright
© Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.Google Scholar
2. Marneros, A. Origin and development of concepts of bipolar mixed states. J Affect Disord. 2001; 67(1–3): 229–240.CrossRefGoogle ScholarPubMed
3. Angst, J, Marneros, A. Bipolarity from ancient to modern times: conception, birth and rebirth. J Affect Disord. 2001; 67(1–3): 3–19.CrossRefGoogle ScholarPubMed
4. Himmelhoch, JM, Mulla, D, Neil, JF, Detre, TP, Kupfer, DJ. Incidence and significance of mixed affective states in a bipolar population. Arch Gen Psychiatry. 1976; 33(9): 1062–1066.CrossRefGoogle Scholar
5. Akiskal, HS, Rosenthal, RH, Rosenthal, TL, Kashgarian, M, Khani, MK, Puzantian, VR. Differentiation of primary affective illness from situational, symptomatic, and secondary depressions. Arch Gen Psychiatry. 1979; 36(6): 635–643.CrossRefGoogle ScholarPubMed
6. McElroy, SL, Keck, PE, Pope, HG, Hudson, JI, Faedda, GL, Swann, AC. Clinical and research implication of the diagnosis of dysphoric or mixed mania or hypomania. Am J Psychiatry. 1992; 149(12): 1633–1644.Google ScholarPubMed
7. Faedda, GL, Marangoni, C, Rginaldi, D. Depressive mixed states: a reappraisal of Koukopoulos’ criteria. J Affect Disord. 2015; 176: 18–23.CrossRefGoogle Scholar
8. Sani, G, Napoletano, F, Vohringer, PA, et al. Mixed depression: clinical features and predictors of its onset associated with antidepressant use. Psychother Psychosom . 2014; 83(4): 213–221.CrossRefGoogle ScholarPubMed
9. Perugi, G, Angst, J, Azorin, J, et al. Mixed features in patients with a major depressive episode: the BRIDGE-II-MIX study. J Clin Psychiatry. 2015; 76(3): e351–e358.CrossRefGoogle Scholar
10. Angst, J, Cui, L, Swendsen, J, et al. Major depressive disorder with subthreshold bipolarity in the National Comorbidity Survey Replication. Am J Psychiatry. 2010; 167(10): 1194–1201.CrossRefGoogle ScholarPubMed
11. Kukopulos, A, Caliari, B, Tundo, A, et al. Rapid cyclers, temperament, and antidepressants. Compr Psychiatry. 1983; 24(3): 249–258.CrossRefGoogle ScholarPubMed
12. Benazzi, F, Akiskal, HS. Psychometric delineation of the most discriminant symptoms of depressive mixed states. Psychiatry Res. 2006; 141(1): 81–88.CrossRefGoogle ScholarPubMed
13. Akiskal, HS, Benazzi, F, Perugi, G, Rihmer, . Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy. J Affect Disord. 2005; 85(3): 245–258.CrossRefGoogle ScholarPubMed
14. Suppes, T, Mintz, J, McElroy, SL, et al. Mixed hypomania in 908 patients with bipolar disorder evaluated prospectively in the Stanley Bipolar Treatment Network: a sex-specific phenomenon. Arch Gen Psychiatry. 2005; 62(10): 1089–1096.CrossRefGoogle ScholarPubMed
15. Goldberg, JF, Perlis, RH, Bowden, CL, et al. Manic symptoms during depressive episodes in 1380 patients with bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2009; 166(2): 173–181.CrossRefGoogle Scholar
16. Miller, S, Suppes, T, Mintz, J, et al. Mixed depression in bipolar disorder: prevalence rate and clinical correlates during naturalistic follow-up in the Stanley Bipolar Network. Am J Psychiatry. 2016; 173(10): 1015–1023.CrossRefGoogle ScholarPubMed
17. Angst, J, Azorin, J, Bowden, C, et al. Prevalence and characteristics of undiagnosed bipolar disorders in patients with major depressive episode. Arch Gen Psychiatry. 2011; 68(8): 791–799.CrossRefGoogle ScholarPubMed
18. Fiedorowicz, J, Endicott, J, Leon, A, Solomon, D, Keller, M, Coryell, W. Subthreshold hypomanic symptoms in progression form unipolar major depression to bipolar disorder. Am J Psychiatry. 2011; 168(1): 40–48.CrossRefGoogle Scholar
19. Zimmermann, P, Brückl, T, Nocon, A, et al. Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity. Arch Gen Psychiatry. 2009; 66(12): 1341–1352.CrossRefGoogle ScholarPubMed
20. Liu, X, Jiang, K. Should major depressive disorder with mixed features be classified as bipolar disorder? Shanghai Arch of Psychiatry. 2014; 26(5): 294–296.Google ScholarPubMed
21. Perlis, R, Uher, R, Ostacher, M, et al. Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder. Arch Gen Psychiatry. 2011; 68(4): 351–360.CrossRefGoogle ScholarPubMed
22. Serra, G, Koukopoulos, A, De Chiara, L, et al. Features preceding diagnosis of bipolar versus major depressive disorders. J Affect Disord. 2015; 173: 134–142.CrossRefGoogle ScholarPubMed
23. Perlis, R, Cusin, C, Fava, M. Proposed DSM-5 mixed features are associated with greater likelihood of remission in out-patients with major depressive disorder. Psychol Med. 2014; 44(7): 1361–1367.CrossRefGoogle ScholarPubMed
24. McIntyre, R, Soczynska, J, Cha, D, et al. The prevalence and illness characteristics of DSM-5-defined “mixed feature specifier” in adults with major depressive disorder and bipolar disorder: results from the International Mood Disorders Collaborative Project. J Affect Disord. 2015; 172: 259–264.CrossRefGoogle ScholarPubMed
25. Smith, D, Forty, L, Russell, E, et al. Sub-threshold manic symptoms in recurrent major depressive disorder are a marker for poor outcome. Acta Psychiatr Scand. 2009; 119(4): 325–329.CrossRefGoogle ScholarPubMed
26. Balázs, 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(2–3): 133–138.CrossRefGoogle ScholarPubMed
27. Swann, A, Lafer, B, Perugi, G, et al. Bipolar mixes states: an International Society for Bipolar Disorders task force report of symptom structure, course of illness, and diagnosis. Am J Psychiatry. 2013; 170(1): 31–42.CrossRefGoogle ScholarPubMed
28. Koukopoulos, A, Sani, G. DSM-5 criteria for depression with mixed features: a farewell to mixed depression. Acta Psychiatr Scand. 2014; 129(1): 4–16.CrossRefGoogle ScholarPubMed
29. Suppes, T, Silva, R, Cucchiaro, J, et al. Lurasidone for the treatment of major depressive disorder with mixed features: a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2016; 173(4): 400–407.CrossRefGoogle ScholarPubMed
30. Benazzi, F, Koukopoulous, , Akiskal, H. Toward a validation of a new definition of agitated depression as a mixed state (mixed depression). Eur Psychiatry. 2004; 19(2): 85–90.CrossRefGoogle Scholar
31. Benazzi, F. Reviewing the diagnostic validity and utility of mixed depression (depressive mixed states). European Psychiatry. 2008; 23(1): 40–48.CrossRefGoogle ScholarPubMed
32. Benazzi, F, Akiskal, H. Delineating bipolar II mixed states in the Ravenna-San Diego collaborative study: the relative prevalence and diagnostic significance of hypomanic features during major depressive episodes. J Affect Disord. 2001; 67(1–3): 115–122.CrossRefGoogle Scholar
33. Clementz, B, Sweeney, J, Hamm, J, et al. Identification of distinct psychosis biotypes using brain-based biomarkers. Am J Psychiatry. 2015; 173(4): 373–384.CrossRefGoogle ScholarPubMed
34. Williams, L. Precision psychiatry: a neural circuit taxonomy for depression and anxiety. Lancet Psychiatry. 2016; 3(5): 472–480.CrossRefGoogle ScholarPubMed
35. Altshuler, L, Sugar, C, McElroy, S, et al. Switch rates during lithium monotherapy, sertraline monotherapy and lithium/sertraline combination therapy for the acute treatment of bipolar II depression: a randomized double-blind comparison. Am J Psychiatry. 2017; 174(3): 266–276.CrossRefGoogle ScholarPubMed
36. Amsterdam, J, Shults, J. Efficacy and safety of long-term fluoxetine versus lithium monotherapy of bipolar II disorder: a randomized, double-blind, placebo-substitution study. Am J Psychiatry. 2010; 167(7): 792–800.CrossRefGoogle ScholarPubMed
37. Suppes, T. Is there a role for antidepressants in the treatment of bipolar II depression? Am J Psychiatry. 2010; 167(7): 738–740.CrossRefGoogle Scholar