Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-27T15:44:34.987Z Has data issue: false hasContentIssue false
  • English
  • Français

A pragmatic approach to the diagnosis and treatment of mixed features in adults with mood disorders

Published online by Cambridge University Press:  03 January 2017

Roger S. McIntyre ,
Yena Lee  and
Rodrigo B. Mansur
Roger S. McIntyre*
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
Yena Lee
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Rodrigo B. Mansur
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
*
*Address for correspondence: Dr. Roger S. McIntyre, MD, FRCPC, Professor of Psychiatry and Pharmacology, University of Toronto, Head, Mood Disorders Psychopharmacology Unit, University Health Network, Executive Director, Brain and Cognition Discovery Foundation, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Mixed features specifier (MFS) is a new nosological entity defined and operationalized in the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition. The impetus to introduce the MFS and supplant mixed states was protean, including the lack of ecological validity, high rates of misdiagnosis, and guideline discordant treatment for mixed states. Mixed features specifier identifies a phenotype in psychiatry with greater illness burden, as evidenced by earlier age at onset, higher episode frequency and chronicity, psychiatric and medical comorbidity, suicidality, and suboptimal response to conventional antidepressants. Mixed features in psychiatry have historical, conceptual, and nosological relevance; MFS according to DSM-5, is inherently neo-Kraepelinian insofar as individuals with either Major Depressive Disorder (MDD) or Bipolar Disorder (BD) may be affected by MFS. Clinicians are encouraged to screen all patients presenting with a major depressive episode (or hypomanic episode) for MFS. Although “overlapping symptoms” were excluded from the diagnostic criteria (eg, agitation, anxiety, irritability, insomnia), clinicians are encouraged to probe for these nonspecific symptoms as a possible proxy of co-existing MFS. In addition to conventional antidepressants, second generation antipsychotics and/or conventional mood stabilizers (eg, lithium) may be considered as first-line therapies for individuals with a depressive episode as part of MDD or BD with mixed features.

Keywords

Bipolar disorderbipolar spectrumdepression spectrummajor depressive disordermixed featuresmixed states
Type
CME Review Article
Information
CNS Spectrums , Volume 21 , Supplement S1: CME SUPPLEMENT , December 2016 , pp. 25 - 33
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.)

Footnotes

This activity is supported by an unrestricted educational grant from Sunovion Pharmaceuticals Inc.

References

1. Targum, SD, Suppes, T, Pendergrass, JC, et al. Major depressive disorder with subthreshold hypomania (mixed features): clinical characteristics of patients entered in a multiregional, placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2016; 68: 9–14.Google Scholar
2. Freedman, R, Lewis, DA, Michels, R, et al. The initial field trials of DSM-5: new blooms and old thorns. Am J Psychiatry. 2013; 170(1): 1–5.CrossRefGoogle ScholarPubMed
3. McIntyre, RS. Practical approaches in the management of bipolar depression: overcoming challenges and avoiding pitfalls. Evidence-based treatment of bipolar disorder, bipolar depression, and mixed features. J Fam Pract. 2015; 64(6 Suppl): S16–S23.Google Scholar
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.Google Scholar
5. Modell, S, Huber, J, Holsboer, F, Lauer, CJ. The Munich Vulnerability Study on Affective Disorders: risk factors for unipolarity versus bipolarity. J Affect Disord. 2003; 74(2): 173–184.Google Scholar
6. Goldberg, JF, Perlis, RH, Bowden, CL, et al. Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2009; 166(2): 173–181.Google Scholar
7. 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.Google Scholar
8. Suppes, T, Mintz, J, McElroy, SL, et al. Mixed hypomania in 908 patients with bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar Treatment Network: a sex-specific phenomenon. Arch Gen Psychiatry. 2005; 62(10): 1089–1096.CrossRefGoogle ScholarPubMed
9. Judd, LL, Paulus, MP, Wells, KB, Rapaport, MH. Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Am J Psychiatry. 1996; 153(11): 1411–1417.Google Scholar
10. Florida Best Practice Psychotherapeutic Medication Guidelines for Adults. Florida Medicaid Drug Therapy Management Program for Behavioral Health; 2015. http://www.medicaidmentalhealth.org/_assets/file/Guidelines/Web_2015-Psychotherapeutic%20Medication%20Guidelines%20for%20Adults_Final_Approved1.pdf.Google Scholar
11. Salvatore, P, Baldessarini, RJ, Centorrino, F, et al. Weygandt’s On the Mixed States of Manic-Depressive Insanity: a translation and commentary on its significance in the evolution of the concept of bipolar disorder. Harv Rev Psychiatry. 2002; 10(5): 255–275.Google Scholar
12. 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.Google Scholar
13. 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.Google Scholar
14. Angst, J, Gamma, A, Benazzi, F, Ajdacic, V, Eich, D, Rossler, W. Toward a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord. 2003; 73(1–2): 133–146.Google Scholar
15. Malhi, GS, Lampe, L, Coulston, CM, et al. Mixed state discrimination: a DSM problem that wont go away? J Affect Disord. 2014; 158: 8–10.Google Scholar
16. 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. 2014; 172C: 259–264.Google Scholar
17. 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.Google Scholar
18. Zimmerman, M, Chelminski, I, Young, D, Dalrymple, K, Martinez, JH. A clinically useful self-report measure of the DSM-5 mixed features specifier of major depressive disorder. J Affect Disord. 2014; 168: 357–362.Google Scholar
19. Rosenblat, JD, McIntyre, RS. Treatment recommendations for DSM-5-defined mixed features. CNS Spectr. In press. DOI: 10.1017/S1092852916000432.Google Scholar
20. Maj, M, Pirozzi, R, Magliano, L, Fiorillo, A, Bartoli, L. Agitated “unipolar” major depression: prevalence, phenomenology, and outcome. J Clin Psychiatry. 2006; 67(5): 712–719.Google Scholar
21. Patkar, A, Gilmer, W, Pae, CU, et al. A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state. PLoS One. 2012; 7(4): e34757.Google Scholar
22. 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.Google Scholar
23. McIntyre, RS, Cha, DS, Soczynska, JK, et al. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety. 2013; 30(6): 515–527.Google Scholar
24. McIntyre, RS, Alsuwaidan, M, Soczynska, JK, et al. The effect of lisdexamfetamine dimesylate on body weight, metabolic parameters, and attention deficit hyperactivity disorder symptomatology in adults with bipolar I/II disorder. Hum Psychopharmacol. 2013; 28(5): 421–427.CrossRefGoogle ScholarPubMed
25. Fiedorowicz, JG, Endicott, J, Solomon, DA, et al. Course of illness following prospectively observed mania or hypomania in individuals presenting with unipolar depression. Bipolar Disord. 2012; 14(16): 664–671.Google Scholar