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Treatment of mixed features in bipolar disorder

Published online by Cambridge University Press:  13 September 2016

Joshua D. Rosenblat  and
Roger S. McIntyre
Joshua D. Rosenblat
Affiliation:
Mood Disorder Psychopharmacology Unit, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
Roger S. McIntyre*
Affiliation:
Mood Disorder Psychopharmacology Unit, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
*
*Address for correspondence: Roger S. McIntyre, M.D., FRCPC, Professor of Psychiatry and Pharmacology, University of Toronto, Head, Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON M5T 2S8, Canada. (Email: [email protected])
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Abstract

Mood episodes with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)–defined mixed features are highly prevalent in bipolar disorder (BD), affecting ~40% of patients during the course of illness. Mixed states are associated with poorer clinical outcomes, greater treatment resistance, higher rates of comorbidity, more frequent mood episodes, and increased rates of suicide. The objectives of the current review are to identify, summarize, and synthesize studies assessing the efficacy of treatments specifically for BD I and II mood episodes (ie, including manic, hypomanic, and major depressive episodes) with DSM-5–defined mixed features. Two randomized controlled trials (RCTs) and 6 post-hoc analyses were identified, all of which assessed the efficacy of second-generation antipsychotics (SGAs) for the acute treatment of BD mood episodes with mixed features. Results from these studies provide preliminary support for SGAs as efficacious treatments for both mania with mixed features and bipolar depression with mixed features. However, there are inadequate data to definitively support or refute the clinical use of specific agents. Conventional mood stabilizing agents (eg, lithium and divalproex) have yet to have been adequately studied in DSM-5–defined mixed features. Further study is required to assess the efficacy, safety, and tolerability of treatments specifically for BD mood episodes with mixed features.

Keywords

Antipsychoticsbipolar disorderDSM-5mixed episodemixed featuresmixed statesmood stabilizers
Type
Review Articles
Information
CNS Spectrums , Volume 22 , Issue 2: Theme: Mixed features in major depressive episodes , April 2017 , pp. 141 - 146
Copyright
© Cambridge University Press 2016 

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References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.Google Scholar
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
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. Castle, DJ. Bipolar mixed states: still mixed up? Curr Opin Psychiatry. 2014; 27(1): 38–42.Google Scholar
5. Benvenuti, A, Miniati, M, Callari, A, Giorgi Mariani, M, Mauri, M, Dell’Osso, L. Mood spectrum model: evidence reconsidered in the light of DSM-5. World J Psychiatry. 2015; 5(1): 126–137.CrossRefGoogle ScholarPubMed
6. Kessing, LV. The prevalence of mixed episodes during the course of illness in bipolar disorder. Acta Psychiatr Scand. 2008; 117(3): 216–224.Google Scholar
7. 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.Google Scholar
8. Verdolini, N, Agius, M, Ferranti, L, Moretti, P, Piselli, M, Quartesan, R. The state of the art of the DSM-5 “with mixed features” specifier. The Scientific World Journal. 2015; 2015: 757258.Google Scholar
9. Shim, IH, Woo, YS, Jun, TY, Bahk, WM. Mixed-state bipolar I and II depression: time to remission and clinical characteristics. J Affect Disord. 2014; 152–154: 340–346.CrossRefGoogle ScholarPubMed
10. Undurraga, J, Baldessarini, RJ, Valenti, M, Pacchiarotti, I, Vieta, E. Suicidal risk factors in bipolar I and II disorder patients. J Clin Psychiatry. 2012; 73(6): 778–782.CrossRefGoogle ScholarPubMed
11. Shim, IH, Woo, YS, Bahk, WM. Prevalence rates and clinical implications of bipolar disorder “with mixed features” as defined by DSM-5. J Affect Disord. 2015; 173: 120–125.CrossRefGoogle Scholar
12. Popovic, D, Vieta, E, Azorin, JM, et al. Suicide attempts in major depressive episode: evidence from the BRIDGE-II-Mix study. Bipolar Disord. 2015; 17(7): 795–803.CrossRefGoogle ScholarPubMed
13. Benazzi, F, Berk, M, Frye, MA, Wang, W, Barraco, A, Tohen, M. Olanzapine/fluoxetine combination for the treatment of mixed depression in bipolar I disorder: a post hoc analysis. J Clin Psychiatry. 2009; 70(10): 1424–1431.Google Scholar
14. 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.CrossRefGoogle ScholarPubMed
15. Pae, CU, Patkar, AA, Gilmer, W, Holtzman, N, Thommi, SB, Ghaemi, SN. Predictors of response to ziprasidone: results from a 6-week randomized double-blind, placebo-controlled trial for acute depressive mixed state. Pharmacopsychiatry. 2012; 45(4): 152–155.Google ScholarPubMed
16. Tohen, M, Kanba, S, McIntyre, RS, Fujikoshi, S, Katagiri, H. Efficacy of olanzapine monotherapy in the treatment of bipolar depression with mixed features. J Affect Disord. 2014; 164: 57–62.CrossRefGoogle ScholarPubMed
17. McIntyre, RS, Cucchiaro, J, Pikalov, A, Kroger, H, Loebel, A. Lurasidone in the treatment of bipolar depression with mixed (subsyndromal hypomanic) features: post hoc analysis of a randomized placebo-controlled trial. J Clin Psychiatry. 2015; 76(4): 398–405.CrossRefGoogle ScholarPubMed
18. McIntyre, RS, Tohen, M, Berk, M, Zhao, J, Weiller, E. DSM-5 mixed specifier for manic episodes: evaluating the effect of depressive features on severity and treatment outcome using asenapine clinical trial data. J Affect Disord. 2013; 150(2): 378–383.Google Scholar
19. Tohen, M, McIntyre, RS, Kanba, S, Fujikoshi, S, Katagiri, H. Efficacy of olanzapine in the treatment of bipolar mania with mixed features defined by DSM-5. J Affect Disord. 2014; 168: 136–141.Google Scholar
20. Suppes, T, Ketter, TA, Gwizdowski, IS, et al. First controlled treatment trial of bipolar II hypomania with mixed symptoms: quetiapine versus placebo. J Affect Disord. 2013; 150(1): 37–43.Google Scholar
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.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. 2015 Florida Best Practice Psychotherapeutic Medication Guidelines for Adults. 2015. http://medicaidmentalhealth.org/ViewGuideline.cfm?GuidelineID=97. Accessed April 20, 2016.Google Scholar
24. Fagiolini, A, Coluccia, A, Maina, G, et al. Diagnosis, epidemiology and management of mixed states in bipolar disorder. CNS Drugs. 2015; 29(9): 725–740.CrossRefGoogle ScholarPubMed
25. Fountoulakis, KN, Kontis, D, Gonda, X, Siamouli, M, Yatham, LN. Treatment of mixed bipolar states. Int J Neuropsychopharmacol. 2012; 15(7): 1015–1026.Google Scholar
26. McIntyre, RS, Yoon, J. Efficacy of antimanic treatments in mixed states. Bipolar Disord. 2012; 14(Suppl 2): 22–36.Google Scholar
27. Muralidharan, K, Ali, M, Silveira, LE, et al. Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: a meta-analysis of placebo-controlled trials. J Affect Disord. 2013; 150(2): 408–414.Google Scholar
28. McElroy, SL, Martens, BE, Creech, RS, et al. Randomized, double-blind, placebo-controlled study of divalproex extended release loading monotherapy in ambulatory bipolar spectrum disorder patients with moderate-to-severe hypomania or mild mania. J Clin Psychiatry. 2010; 71(5): 557–565.Google Scholar