Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-25T18:48:58.154Z Has data issue: false hasContentIssue false
  • English
  • Français

What is the role of conventional antidepressants in the treatment of major depressive episodes with Mixed Features Specifier?

Published online by Cambridge University Press:  10 November 2016

Gianni L. Faedda  and
Ciro Marangoni
Gianni L. Faedda*
Affiliation:
Lucio Bini Mood Disorders Center, New York, New York, USA
Ciro Marangoni
Affiliation:
Centro Lucio Bini, Rome, Italy
*
*Address for correspondence: Gianni L. Faedda, Lucio Bini Mood Disorders Center, 245 E. 50th St., New York, NY 10022, USA. (Email: moodcenter@gmail.com)
Get access Rights & Permissions [Opens in a new window]

Abstract

The newly introduced Mixed Features Specifier of Major Depressive Episode and Disorder (MDE/MDD) is especially challenging in terms of pharmacological management. Prior to the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the symptoms of the mixed features specifier were intradepressive hypomanic symptoms, always and only associated with bipolar disorder (BD).

Intradepressive hypomanic symptoms, mostly referred to as depressive mixed states (DMX), have been poorly characterized, and their treatment offers significant challenges. To understand the diagnostic context of DMX, we trace the nosological changes and collocation of intradepressive hypomanic symptoms, and examine diagnostic and prognostic implications of such mixed features.

One of the reasons so little is known about the treatment of DMX is that depressed patients with rapid cycling, substance abuse disorder, and suicidal ideation/attempts are routinely excluded from clinical trials of antidepressants. The exclusion of DMX patients from clinical trials has prevented an assessment of the safety and tolerability of short- and long-term use of antidepressants. Therefore, the generalization of data obtained in clinical trials for unipolar depression to patients with intradepressive hypomanic features is inappropriate and methodologically flawed.

A selective review of the literature shows that antidepressants alone have limited efficacy in DMX, but they have the potential to induce, maintain, or worsen mixed features during depressive episodes in BD. On the other hand, preliminary evidence supports the effective use of some atypical antipsychotics in the treatment of DMX.

Keywords

Antidepressantbipolar disordermajor depressionmixed featuresmixed states
Type
Opinions
Information
CNS Spectrums , Volume 22 , Issue 2: Theme: Mixed features in major depressive episodes , April 2017 , pp. 120 - 125
Copyright
© Cambridge University Press 2016 

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. Koukopoulos, A, Sani, G, Koukopoulos, AE, Manfredi, G, Pacchiarotti, I, Girardi, P. Melancholia agitata and mixed depression. Acta Psychiatr Scand Suppl. 2007; 433: 50–57.CrossRefGoogle Scholar
2. Spitzer, RL, Endicott, J, Robins, E. Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry. 1978; 35(6): 773–782.CrossRefGoogle ScholarPubMed
3. Swann, AC, Lafer, B, Perugi, G, 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(1): 31–42.CrossRefGoogle ScholarPubMed
4. Koukopoulos, A, Faedda, G, Proietti, R, D’Amico, S, de Pisa, E, Simonetto, C. Mixed depressive syndrome. Encephale. 1992; 18(1): 19–21.Google ScholarPubMed
5. Sani, G, Vöhringer, P, Napoletano, F, et al. Koukopoulos’ diagnostic criteria for mixed depression: a validation study. J Affect Disord. 2014; 164: 14–18.CrossRefGoogle ScholarPubMed
6. 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
7. Smith, DJ, 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
8. 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
9. 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
10. Nusslock, R, Frank, E. Subthreshold bipolarity: diagnostic issues and challenges. Bipolar Disord. 2011; 13(7–8): 587–603.CrossRefGoogle ScholarPubMed
11. McIntyre, RS, Soczynska, JK, Cha, DS, 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
12. Perugi, G, Angst, J, Azorin, JM, 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
13. 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
14. Faedda, GL, Marangoni, C, Serra, G, et al. Precursors of bipolar disorders: a systematic literature review of prospective studies. J Clin Psychiatry. 2015; 76(5): 614–624.CrossRefGoogle ScholarPubMed
15. Perlis, RH, Ostacher, MJ, Goldberg, JF, et al. Transition to mania during treatment of bipolar depression. Neuropsychopharmacology. 2010; 35(13): 2545–2552.CrossRefGoogle ScholarPubMed
16. Frye, MA, Helleman, G, McElroy, SL, et al. Correlates of treatment-emergent mania associated with antidepressant treatment in bipolar depression. Am J Psychiatry. 2009; 166(2): 164–172.CrossRefGoogle ScholarPubMed
17. 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(3): 245–258.CrossRefGoogle ScholarPubMed
18. Goldberg, JF, Perlis, RH, Ghaemi, SN, 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(9): 1348–1355.CrossRefGoogle ScholarPubMed
19. Fornaro, M, Martino, M, De Pasquale, C, Moussaoui, D. The argument of antidepressant drugs in the treatment of bipolar depression: mixed evidence or mixed states? Expert Opin Pharmacother. 2012; 13(14): 2037–2051.CrossRefGoogle ScholarPubMed
20. Sani, G, Napoletano, F, Vöhringer, 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
21. Perlis, RH, 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
22. Pacchiarotti, I, Bond, DJ, Baldessarini, RJ, et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry. 2013; 170(11): 1249–1262.CrossRefGoogle ScholarPubMed
23. Fornaro, M, Stubbs, B, De Berardis, D, et al. Atypical antipsychotics in the treatment of acute bipolar depression with mixed features: a systematic review and exploratory meta-analysis of placebo-controlled clinical trials. Int J Mol Sci. 2016; 17(2): 241.CrossRefGoogle ScholarPubMed
24. Sachs, GS, Nierenberg, AA, Calabrese, JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007; 356(17): 1711–1722.CrossRefGoogle ScholarPubMed
25. Koukopoulos, A, Sani, G, Ghaemi, SN. Mixed features of depression: why DSM-5 is wrong (and so was DSM-IV). Br J Psychiatry. 2013; 203(1): 3–5.CrossRefGoogle ScholarPubMed
26. Michaux, L, Saulnier, M, Bureau, G. A propos des Etats Mixtes. Sem Hop Paris. 1950; 83: 4275–4286.Google Scholar
27. Campbell, JD. Mixed and manic phases of manic-depressive psychosis. In. Manic Depressive Disease. Philadelphia: Lippincott; 1953.Google Scholar
28. Glassman, AH. Depression, delusions, and drug response. Am J Psychiatry. 1975; 132(7): 716–719.Google ScholarPubMed
29. Wehr, TA, Goodwin, FK. Rapid cycling in manic-depressives induced by tricyclic antidepressants. Arch Gen Psychiatry. 1979; 36: 555–559.CrossRefGoogle ScholarPubMed
30. Kukopulos, A, Reginaldi, D, Laddomada, P, Floris, G, Serra, G, Tondo, L. Course of the manic-depressive cycle and changes caused by treatment. Pharmakopsychiatr Neuropsychopharmakol. 1980; 13(4): 156–167.CrossRefGoogle ScholarPubMed
31. Tondo, L, Laddomada, P, Serra, G, Minnai, G, Kukopulos, A. Rapid cyclers and antidepressants. Int Pharmacopsychiatry. 1981; 16(2): 119–123.CrossRefGoogle ScholarPubMed
32. Akiskal, HS, Mallya, G. Criteria for the “soft” bipolar spectrum: treatment implications. Psychopharmacol Bull. 1987; 23(1): 68–73.Google ScholarPubMed
33. Faedda, GL, Marangoni, C, Reginaldi, D. Depressive mixed states: a reappraisal of Koukopoulos’ criteria. J Affect Disord. 2015; 176: 18–23.CrossRefGoogle Scholar