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Fortschr Neurol Psychiatr 2015; 83(11): 606-615
DOI: 10.1055/s-0041-109017
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Die gemischte Episode bei bipolarer affektiver Störung – Änderungen im DSM-5 und aktuelle Behandlungsempfehlungen

Mixed Episodes in Bipolar Disorders – Changes in DSM-5 and Treatment Recommendations
S. Köhler
1   Charité, Klinik für Psychiatrie und Psychotherapie, Campus Mitte
,
L. A. Stöver
1   Charité, Klinik für Psychiatrie und Psychotherapie, Campus Mitte
2   Psychiatrische Universitätsklinik der Charité im St. Hedwig-Krankenhaus, Berlin
,
P. Sterzer
1   Charité, Klinik für Psychiatrie und Psychotherapie, Campus Mitte
› Author Affiliations
Further Information

Publication History

Publication Date:
03 December 2015 (online)

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Zusammenfassung

Die gemischte Episode stellt eine besondere Behandlungsbedingung im Rahmen affektiver Erkrankungen dar, die durch einen komplizierten und erschwerten Behandlungsverlauf (u. a. erhöhte Suizidrate) sowie ein schlechteres Therapieansprechen gekennzeichnet ist. Das DSM-5 hat als eine wesentliche Veränderung die Diagnose einer gemischten Episode abgeschafft und stattdessen sogenannte Episoden mit gemischten Merkmalen eingeführt. Dadurch sinkt die diagnostische Schwelle deutlich. Bezüglich der Pharmakotherapie gemischter Episoden ist die Datenlage insgesamt nicht ausreichend, jedoch zeigen sich Vorteile für die Behandlung mit atypischen Antipsychotika sowie Valproat und Carbamazepin.

Abstract

Mixed episodes in the course of affective disorders are challenging for any psychiatrist, because they are often characterized by a complicated and difficult treatment course (e. g. higher suicide rates) and a worse treatment outcome. In DSM-5, one of the main changes is that the diagnosis of a mixed episode was disestablished and replaced with affective episodes with so called “mixed features”. This alteration markedly reduces the diagnostic threshold. The available literature on pharmacological treatment of mixed episodes is not sufficient; however, treatment with atypical antipsychotics, especially olanzapine and aripiprazole and the mood stabilizers valproate and carmabazepine has proved to be beneficial.

Schlüsselwörter

gemischte Episode - DSM-5 - Behandlung

Key words

mixed episode - DSM-5 - treatment
 

  • Literatur

  • 1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Arlington, VA: American Psychiatric Publishing; 2013
    Google Scholar
  • 2 Kraepelin E. Psychiatrie. 7. Aufl. Leipzig: Barth; 1904
    Google Scholar
  • 3 Weygandt W. Über die Mischzustände des manisch-depressiven Irreseins. München: JF Lehmann; 1899
    Google Scholar
  • 4 Schneider K. Klinische Psychopathologie. Stuttgart: Thieme; 1931–2007
    Google Scholar
  • 5 Himmelhoch JM, Mulla D, Neil JF et al. Incidence and significance of mixed affective states in a bipolar population. Arch Gen Psychiatry 1976; 33: 1062-1066
    CrossrefPubMedGoogle Scholar
  • 6 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: 173-181
    CrossrefPubMedGoogle Scholar
  • 7 Suppes T, Eudicone J, McQuade R et al. Efficacy and safety of aripiprazole in subpopulations with acute manic or mixed episodes of bipolar I disorder. J Affect Disord 2008; 107: 145-154
    CrossrefPubMedGoogle Scholar
  • 8 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: 31-42
    CrossrefPubMedGoogle Scholar
  • 9 Akiskal HS, Bourgeois ML, Angst J et al. Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000; 59 (Suppl. 01) S5-S30
    CrossrefPubMedGoogle Scholar
  • 10 Cassidy F, Yatham LN, Berk M et al. Pure and mixed manic subtypes: a review of diagnostic classification and validation. Bipolar Disord 2008; 10: 131-143
    CrossrefPubMedGoogle Scholar
  • 11 Vieta E, Morralla C. Prevalence of mixed mania using 3 definitions. J Affect Disord 2010; 125: 61-73
    CrossrefPubMedGoogle Scholar
  • 12 Balazs J, Benazzi F, Rihmer Z et al. The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention. J Affect Disord 2006; 91: 133-138
    CrossrefPubMedGoogle Scholar
  • 13 Baldessarini RJ, Salvatore P, Khalsa HM et al. Dissimilar morbidity following initial mania versus mixed-states in type-I bipolar disorder. J Affect Disord 2010; 126: 299-302
    CrossrefPubMedGoogle Scholar
  • 14 Cassidy F, Ahearn E, Carroll BJ. A prospective study of inter-episode consistency of manic and mixed subtypes of bipolar disorder. J Affect Disord 2001; 67: 181-185
    CrossrefPubMedGoogle Scholar
  • 15 Sato T, Bottlender R, Sievers M et al. Evaluating the inter-episode stability of depressive mixed states. J Affect Disord 2004; 81: 103-113
    CrossrefPubMedGoogle Scholar
  • 16 Benazzi F. Bipolar disorder--focus on bipolar II disorder and mixed depression. Lancet 2007; 369: 935-945
    CrossrefPubMedGoogle Scholar
  • 17 Pacchiarotti I, Nivoli AM, Mazzarini L et al. The symptom structure of bipolar acute episodes: in search for the mixing link. J Affect Disord 2013; 149: 56-66
    CrossrefPubMedGoogle Scholar
  • 18 Nusslock R, Frank E. Subthreshold bipolarity: diagnostic issues and challenges. Bipolar Disord 2011; 13: 587-603
    CrossrefPubMedGoogle Scholar
  • 19 Bschor T, Angst J, Azorin JM et al. Are bipolar disorders underdiagnosed in patients with depressive episodes? Results of the multicenter BRIDGE screening study in Germany. J Affect Disord 2012; 142: 45-52
    CrossrefPubMedGoogle Scholar
  • 20 Perugi G, Medda P, Reis J et al. Clinical subtypes of severe bipolar mixed states. J Affect Disord 2013; 151: 1076-1082
    CrossrefPubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Koukopoulos A, Sani G. DSM-5 criteria for depression with mixed features: a farewell to mixed depression. Acta Psychiatr Scand 2014; 129: 4-16
    CrossrefPubMedGoogle Scholar
  • 23 Perugi G, Quaranta G, Dell'Osso L. The significance of mixed States in depression and mania. Curr Psychiatry Rep 2014; 16: 486
    CrossrefPubMedGoogle Scholar
  • 24 Pacchiarotti I, Mazzarini L, Kotzalidis GD et al. Mania and depression. Mixed, not stirred. J Affect Disord 2011; 133: 105-113
    CrossrefPubMedGoogle Scholar
  • 25 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: 1348-1355
    CrossrefPubMedGoogle Scholar
  • 26 Köhler S, Gaus S, Bschor T. The challenge of treatment in bipolar depression: evidence from clinical guidelines, treatment recommendations and complex treatment situations. Pharmacopsychiatry 2014; 47: 53-59
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Shim IH, Woo YS, Jun TY et al. A reevaluation of the possibility and characteristics in bipolar mania with mixed features: a retrospective chart review. Psychiatry Res 2014; 215: 335-340
    CrossrefPubMedGoogle Scholar
  • 28 Gonzalez-Pinto A, Aldama A, Mosquera F et al. Epidemiology, diagnosis and management of mixed mania. CNS Drugs 2007; 21: 611-626
    CrossrefPubMedGoogle Scholar
  • 29 Cassidy F, Murry E, Forest K et al. Signs and symptoms of mania in pure and mixed episodes. J Affect Disord 1998; 50: 187-201
    CrossrefPubMedGoogle Scholar
  • 30 Swann AC, Secunda SK, Katz MM et al. Specificity of mixed affective states: clinical comparison of dysphoric mania and agitated depression. J Affect Disord 1993; 28: 81-89
    CrossrefPubMedGoogle Scholar
  • 31 Angst J, Gamma A, Bowden CL et al. Evidence-based definitions of bipolar-I and bipolar-II disorders among 5635 patients with major depressive episodes in the Bridge Study: validity and comorbidity. Eur Arch Psychiatry Clin Neurosci 2013; 263: 663-673
    CrossrefPubMedGoogle Scholar
  • 32 Azorin JM, Baraille L, Gerard S et al. Mixed states with predominant manic or depressive symptoms: baseline characteristics and 24-month outcomes of the EMBLEM cohort. J Affect Disord 2013; 146: 369-377
    CrossrefPubMedGoogle Scholar
  • 33 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: 408-414
    CrossrefPubMedGoogle Scholar
  • 34 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: 1194-1201
    CrossrefPubMedGoogle Scholar
  • 35 Swann AC, Bowden CL, Morris D et al. Depression during mania. Treatment response to lithium or divalproex. Arch Gen Psychiatry 1997; 54: 37-42
    CrossrefPubMedGoogle Scholar
  • 36 Bowden CL, Collins MA, McElroy SL et al. Relationship of mania symptomatology to maintenance treatment response with divalproex, lithium, or placebo. Neuropsychopharmacology 2005; 30: 1932-1939
    CrossrefPubMedGoogle Scholar
  • 37 Bowden CL, Swann AC, Calabrese JR et al. A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. J Clin Psychiatry 2006; 67: 1501-1510
    CrossrefPubMedGoogle Scholar
  • 38 Ghaemi SN, Gilmer WS, Goldberg JF et al. Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study. J Clin Psychiatry 2007; 68: 1840-1844
    CrossrefPubMedGoogle Scholar
  • 39 Weisler RH, Kalali AH, Ketter TA et al. A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry 2004; 65: 478-484
    CrossrefPubMedGoogle Scholar
  • 40 Weisler RH, Keck Jr PE, Swann AC et al. Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2005; 66: 323-330
    CrossrefPubMedGoogle Scholar
  • 41 Calabrese JR, Bowden CL, McElroy SL et al. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry 1999; 156: 1019-1023
    PubMedGoogle Scholar
  • 42 Carlson BX, Ketter TA, Sun W et al. Aripiprazole in combination with lamotrigine for the long-term treatment of patients with bipolar I disorder (manic or mixed): a randomized, multicenter, double-blind study (CN138-392). Bipolar Disord 2012; 14: 41-53
    CrossrefPubMedGoogle Scholar
  • 43 Kessing LV, Hellmund G, Andersen PK. An observational nationwide register based cohort study on lamotrigine versus lithium in bipolar disorder. J Psychopharmacol 2012; 26: 644-652
    CrossrefPubMedGoogle Scholar
  • 44 Amann B, Born C, Crespo JM et al. Lamotrigine: when and where does it act in affective disorders? A systematic review. J Psychopharmacol 2011; 25: 1289-1294
    CrossrefPubMedGoogle Scholar
  • 45 Sachs G, Sanchez R, Marcus R et al. Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study. J Psychopharmacol 2006; 20: 536-546
    CrossrefPubMedGoogle Scholar
  • 46 Keck Jr PE, Marcus R, Tourkodimitris S et al. A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry 2003; 160: 1651-1658
    CrossrefPubMedGoogle Scholar
  • 47 McIntyre RS, Cohen M, Zhao J et al. A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states. Bipolar Disord 2009; 11: 673-686
    CrossrefPubMedGoogle Scholar
  • 48 Azorin JM, Sapin C, Weiller E. Effect of asenapine on manic and depressive symptoms in bipolar I patients with mixed episodes: results from post hoc analyses. J Affect Disord 2013; 145: 62-69
    CrossrefPubMedGoogle Scholar
  • 49 Tohen M, Jacobs TG, Grundy SL et al. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzapine HGGW Study Group. Arch Gen Psychiatry 2000; 57: 841-849
    CrossrefPubMedGoogle Scholar
  • 50 Tohen M, McIntyre RS, Kanba S et al. Efficacy of olanzapine in the treatment of bipolar mania with mixed features defined by DSM-5. J Affect Disord 2014; 168: 136-141
    CrossrefPubMedGoogle Scholar
  • 51 Baker RW, Tohen M, Fawcett J et al. Acute dysphoric mania: treatment response to olanzapine versus placebo. J Clin Psychopharmacol 2003; 23: 132-137
    CrossrefPubMedGoogle Scholar
  • 52 Tohen M, Kanba S, McIntyre RS et al. Efficacy of olanzapine monotherapy in the treatment of bipolar depression with mixed features. J Affect Disord 2014; 164: 57-62
    CrossrefPubMedGoogle Scholar
  • 53 Tohen M, Sutton VK, Calabrese JR et al. Maintenance of response following stabilization of mixed index episodes with olanzapine monotherapy in a randomized, double-blind, placebo-controlled study of bipolar 1 disorder. J Affect Disord 2009; 116: 43-50
    CrossrefPubMedGoogle Scholar
  • 54 Vieta E, Nuamah IF, Lim P et al. A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 2010; 12: 230-243
    CrossrefPubMedGoogle Scholar
  • 55 Berwaerts J, Melkote R, Nuamah I et al. A randomized, placebo- and active-controlled study of paliperidone extended-release as maintenance treatment in patients with bipolar I disorder after an acute manic or mixed episode. J Affect Disord 2012; 138: 247-258
    CrossrefPubMedGoogle Scholar
  • 56 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: 37-43
    CrossrefPubMedGoogle Scholar
  • 57 Khanna S, Vieta E, Lyons B et al. Risperidone in the treatment of acute mania: double-blind, placebo-controlled study. Br J Psychiatry 2005; 187: 229-234
    CrossrefPubMedGoogle Scholar
  • 58 Singh V, Bowden CL, Mintz J. Relative effectiveness of adjunctive risperidone on manic and depressive symptoms in mixed mania. Int Clin Psychopharmacol 2013; 28: 91-95
    CrossrefPubMedGoogle Scholar
  • 59 Keck Jr PE, Versiani M, Potkin S et al. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry 2003; 160: 741-748
    CrossrefPubMedGoogle Scholar
  • 60 Potkin SG, Keck Jr PE, Segal S et al. Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial. J Clin Psychopharmacol 2005; 25: 301-310
    CrossrefPubMedGoogle Scholar
  • 61 Stahl S, Lombardo I, Loebel A et al. Efficacy of ziprasidone in dysphoric mania: pooled analysis of two double-blind studies. J Affect Disord 2010; 122: 39-45
    CrossrefPubMedGoogle Scholar
  • 62 Zarate Jr CA, Tohen M. Double-blind comparison of the continued use of antipsychotic treatment versus its discontinuation in remitted manic patients. Am J Psychiatry 2004; 161: 169-171
    CrossrefPubMedGoogle Scholar
  • 63 Krüger S, Young T, Bräunig P. Pharmacotherapy of manic-depressive mixed States. Psychiatr Prax 2006; 33 (Suppl. 01) S32-S39
    Article in Thieme ConnectPubMedGoogle Scholar
  • 64 Tohen M, Chengappa KN, Suppes T et al. Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatry 2002; 59: 62-69
    CrossrefPubMedGoogle Scholar
  • 65 Baker RW, Brown E, Akiskal HS et al. Efficacy of olanzapine combined with valproate or lithium in the treatment of dysphoric mania. Br J Psychiatry 2004; 185: 472-478
    CrossrefPubMedGoogle Scholar
  • 66 Houston JP, Tohen M, Degenhardt EK et al. Olanzapine-divalproex combination versus divalproex monotherapy in the treatment of bipolar mixed episodes: a double-blind, placebo-controlled study. J Clin Psychiatry 2009; 70: 1540-1547
    CrossrefPubMedGoogle Scholar
  • 67 Vieta E, Suppes T, Ekholm B et al. Long-term efficacy of quetiapine in combination with lithium or divalproex on mixed symptoms in bipolar I disorder. J Affect Disord 2012; 142: 36-44
    CrossrefPubMedGoogle Scholar
  • 68 Vieta E, T'Joen C, McQuade RD et al. Efficacy of adjunctive aripiprazole to either valproate or lithium in bipolar mania patients partially nonresponsive to valproate/lithium monotherapy: a placebo-controlled study. Am J Psychiatry 2008; 165: 1316-1325
    CrossrefPubMedGoogle Scholar
  • 69 Yatham LN, Fountoulakis KN, Rahman Z et al. Efficacy of aripiprazole versus placebo as adjuncts to lithium or valproate in relapse prevention of manic or mixed episodes in bipolar I patients stratified by index manic or mixed episode. J Affect Disord 2013; 147: 365-372
    CrossrefPubMedGoogle Scholar