Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-18T10:16:13.023Z Has data issue: false hasContentIssue false
  • English
  • Français

Treatment recommendations for DSM-5–defined mixed features

Published online by Cambridge University Press:  15 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, MD, 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])
Get access Rights & Permissions [Opens in a new window]

Abstract

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) mixed features specifier provides a less restrictive definition of mixed mood states, compared to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), including mood episodes that manifest with subthreshold symptoms of the opposite mood state. A limited number of studies have assessed the efficacy of treatments specifically for DSM-5–defined mixed features in mood disorders. As such, there is currently an inadequate amount of data to appropriately inform evidence-based treatment guidelines of DSM-5 defined mixed features. However, given the high prevalence and morbidity of mixed features, treatment recommendations based on the currently available evidence along with expert opinion may be of benefit. This article serves to provide these interim treatment recommendations while humbly acknowledging the limited amount of evidence currently available. Second-generation antipsychotics (SGAs) appear to have the greatest promise in the treatment of bipolar disorder (BD) with mixed features. Conventional mood stabilizing agents (ie, lithium and divalproex) may also be of benefit; however, they have been inadequately studied. In the treatment of major depressive disorder (MDD) with mixed features, the comparable efficacy of antidepressants versus other treatments, such as SGAs, remains unknown. As such, antidepressants remain first-line treatment of MDD with or without mixed features; however, there are significant safety concerns associated with antidepressant monotherapy when mixed features are present, which merits increased monitoring. Lurasidone is the only SGA monotherapy that has been shown to be efficacious specifically in the treatment of MDD with mixed features. Further research is needed to accurately determine the efficacy, safety, and tolerability of treatments specifically for mood episodes with mixed features to adequately inform future treatment guidelines.

Keywords

Antipsychoticsbipolar disorderDSM-5guidelineslurasidonemajor depressive disordermixed episodemixed featuresmixed statesmood stabilizers
Type
Review Articles
Information
CNS Spectrums , Volume 22 , Issue 2: Theme: Mixed features in major depressive episodes , April 2017 , pp. 147 - 154
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. 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
2. Castle, DJ. Bipolar mixed states: still mixed up? Curr Opin Psychiatry. 2014; 27(1): 38–42.CrossRefGoogle ScholarPubMed
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text rev. Washington, DC: American Psychiatric Association; 1994.Google Scholar
4. 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
5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.Google Scholar
6. Kessing, LV. The prevalence of mixed episodes during the course of illness in bipolar disorder. Acta Psychiatr Scand. 2008; 117(3): 216–224.CrossRefGoogle ScholarPubMed
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: tesults from the International Mood Disorders Collaborative Project. J Affect Disord. 2015; 172: 259–264.CrossRefGoogle 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.CrossRefGoogle 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. Seo, HJ, Wang, HR, Jun, TY, Woo, YS, Bahk, WM. Factors related to suicidal behavior in patients with bipolar disorder: the effect of mixed features on suicidality. Gen Hosp Psychiatry. 2016; 39: 91–96.CrossRefGoogle ScholarPubMed
14. 2015 Florida Best Practice Psychotherapeutic Medication Guidelines for Adults. 2015. http://medicaidmentalhealth.org/ViewGuideline.cfm?GuidelineID=97.Google Scholar
15. Woo, YS, Lee, JG, Jeong, JH, et al. Korean Medication Algorithm Project for Bipolar Disorder: third revision. Neuropsychiatr Dis Treat. 2015; 11: 493–506.Google ScholarPubMed
16. 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
17. Woolf, SH, Grol, R, Hutchinson, A, Eccles, M, Grimshaw, J. Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines. BMJ. 1999; 318(7182): 527–530.CrossRefGoogle ScholarPubMed
18. Lobban, F, Solis-Trapala, I, Symes, W, Morriss, R, ERP Group, University of Liverpool. Early warning signs checklists for relapse in bipolar depression and mania: utility, reliability and validity. J Affect Disord. 2011; 133(3): 413–422.CrossRefGoogle ScholarPubMed
19. Hergueta, T, Weiller, E. Evaluating depressive symptoms in hypomanic and manic episodes using a structured diagnostic tool: validation of a new Mini International Neuropsychiatric Interview (M.I.N.I.) module for the DSM-5 ‘With Mixed Features’ specifier. Int J Bipolar Disord. 2013; 1: 21.CrossRefGoogle ScholarPubMed
20. Kessing, LV, Hansen, HV, Hvenegaard, A, et al. Treatment in a specialised out-patient mood disorder clinic v. standard out-patient treatment in the early course of bipolar disorder: randomised clinical trial. Br J Psychiatry. 2013; 202(3): 212–219.CrossRefGoogle Scholar
21. Bauer, M, Juckel, G, Correll, CU, Leopold, K, Pfennig, A. Diagnosis and treatment in the early illness phase of bipolar disorders. Eur Arch Psychiatry Clin Neurosci. 2008; 258(Suppl 5): 50–54.CrossRefGoogle ScholarPubMed
22. Yatham, LN, Kennedy, SH, Parikh, SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar disord. 2013; 15(1): 1–44.CrossRefGoogle Scholar
23. Schaffer, A, Isometsa, ET, Azorin, JM, et al. A review of factors associated with greater likelihood of suicide attempts and suicide deaths in bipolar disorder: Part II of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder. The Aust N Z J Psychiatry. 2015; 49(11): 1006–1020.CrossRefGoogle ScholarPubMed
24. Leonpacher, AK, Liebers, D, Pirooznia, M, et al. Distinguishing bipolar from unipolar depression: the importance of clinical symptoms and illness features. Psychol Med. 2015; 45(11): 2437–2446.CrossRefGoogle ScholarPubMed
25. Frankland, A, Cerrillo, E, Hadzi-Pavlovic, D, et al. Comparing the phenomenology of depressive episodes in bipolar I and II disorder and major depressive disorder within bipolar disorder pedigrees. J Clin Psychiatry. 2015; 76(1): 32–38; quiz 39.CrossRefGoogle ScholarPubMed
26. Benazzi, F. Bipolar disorder—focus on bipolar II disorder and mixed depression. Lancet. 2007; 369(9565): 935–945.CrossRefGoogle ScholarPubMed
27. Akiskal, HS, Benazzi, F. Family history validation of the bipolar nature of depressive mixed states. J Affect Disord. 2003; 73(1–2): 113–122.CrossRefGoogle ScholarPubMed
28. 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.CrossRefGoogle ScholarPubMed
29. Takeshima, M, Oka, T. Association between the so-called “activation syndrome” and bipolar II disorder, a related disorder, and bipolar suggestive features in outpatients with depression. J Affect Disord. 2013; 151(1): 196–202.CrossRefGoogle ScholarPubMed
30. McMahon, K, Herr, NR, Zerubavel, N, Hoertel, N, Neacsiu, AD. Psychotherapeutic treatment of bipolar depression. Psychiatr Clin North Am. 2016; 39(1): 35–56.CrossRefGoogle ScholarPubMed
31. 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.CrossRefGoogle ScholarPubMed
32. 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.CrossRefGoogle ScholarPubMed
33. 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.CrossRefGoogle ScholarPubMed
34. 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.CrossRefGoogle ScholarPubMed
35. 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.CrossRefGoogle ScholarPubMed
36. McIntyre, RS, Yoon, J. Efficacy of antimanic treatments in mixed states. Bipolar Disord. 2012; 14(Suppl 2): 22–36.CrossRefGoogle ScholarPubMed
37. Fountoulakis, KN, Kontis, D, Gonda, X, Siamouli, M, Yatham, LN. Treatment of mixed bipolar states. Int J Neuropsychopharmacol. 2012; 15(7): 1015–1026.CrossRefGoogle ScholarPubMed
38. Leverich, GS, Altshuler, LL, Frye, MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006; 163(2): 232–239.CrossRefGoogle ScholarPubMed
39. 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
40. Cressman, AM, Macdonald, EM, Huang, A, et al. Prescription stimulant use and hospitalization for psychosis or mania: a population-based study. J Clin Psychopharmacol. 2015; 35(6): 667–671.CrossRefGoogle ScholarPubMed
41. Dundar, Y, Greenhalgh, J, Richardson, M, Dwan, K. Pharmacological treatment of acute agitation associated with psychotic and bipolar disorder: a systematic review and meta-analysis. Hum Psychopharmacol. 2016; 31(4): 268–285.CrossRefGoogle ScholarPubMed
42. Curtin, F, Schulz, P. Clonazepam and lorazepam in acute mania: a Bayesian meta-analysis. J Affect Disord. 2004; 78(3): 201–208.CrossRefGoogle Scholar
43. Durgam, S, Earley, W, Lipschitz, A, et al. An 8-week randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of cariprazine in patients with bipolar I depression. Am J Psychiatry. 2016; 173(3): 271–281.CrossRefGoogle ScholarPubMed
44. Calabrese, JR, Keck, PE Jr, Starace, A, et al. Efficacy and safety of low- and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study. J Clin Psychiatry. 2015; 76(3): 284–292.CrossRefGoogle ScholarPubMed
45. Medda, P, Toni, C, Mariani, MG, De Simone, L, Mauri, M, Perugi, G. Electroconvulsive therapy in 197 patients with a severe, drug-resistant bipolar mixed state: treatment outcome and predictors of response. J Clin Psychiatry. 2015; 76(9): 1168–1173.CrossRefGoogle ScholarPubMed
46. Valenti, M, Benabarre, A, Garcia-Amador, M, Molina, O, Bernardo, M, Vieta, E. Electroconvulsive therapy in the treatment of mixed states in bipolar disorder. Eur Psychiatry. 2008; 23(1): 53–56.CrossRefGoogle ScholarPubMed
47. 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
48. 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
49. 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.CrossRefGoogle ScholarPubMed
50. 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
51. 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
52. Yatham, LN, Paulsson, B, Mullen, J, Vagero, AM. Quetiapine versus placebo in combination with lithium or divalproex for the treatment of bipolar mania. J Clin Psychopharmacol. 2004; 24(6): 599–606.CrossRefGoogle ScholarPubMed
53. Calabrese, JR, Keck, PE Jr, Macfadden, W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005; 162(7): 1351–1360.CrossRefGoogle ScholarPubMed
54. Lam, RW, Kennedy, SH, Grigoriadis, S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009; 117(Suppl 1): S26–S43.CrossRefGoogle Scholar
55. 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
56. Citrome, L, Ketter, TA, Cucchiaro, J, Loebel, A. Clinical assessment of lurasidone benefit and risk in the treatment of bipolar I depression using number needed to treat, number needed to harm, and likelihood to be helped or harmed. J Affect Disord. 2014; 155: 20–27.CrossRefGoogle ScholarPubMed
57. McElroy, SL, Keck, PE Jr. Metabolic syndrome in bipolar disorder: a review with a focus on bipolar depression. J Clin Psychiatry. 2014; 75(1): 46–61.CrossRefGoogle ScholarPubMed
58. McIntyre, RS, Danilewitz, M, Liauw, SS, et al. Bipolar disorder and metabolic syndrome: an international perspective. J Affect Disord. 2010; 126(3): 366–387.CrossRefGoogle ScholarPubMed
59. McIntyre, RS, Konarski, JZ. Tolerability profiles of atypical antipsychotics in the treatment of bipolar disorder. J Clin Psychiatry. 2005; 66(Suppl 3): 28–36.Google ScholarPubMed
60. Goldstein, BI, Carnethon, MR, Matthews, KA, et al. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2015; 132(10): 965–986.CrossRefGoogle ScholarPubMed