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Pharmakologische Behandlung der bipolaren Depression

Evidenz aus klinischen Leitlinien und Behandlungsempfehlungen

Pharmaceutical treatment of bipolar depression

Evidence from clinical guidelines and treatment recommendations

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Zusammenfassung

Die Behandlung der bipolaren Depression stellt die Ärzte im klinischen Alltag vor teilweise komplexe Entscheidungen. Die beste Evidenz in der pharmakologischen Behandlung besteht für Quetiapin, eingeschränkt auch für das hierfür nicht zugelassene Lamotrigin (insbesondere auch in der Kombination mit Lithium), Carbamazepin und Olanzapin. Die Wirksamkeit und Empfehlung von Antidepressiva in der Behandlung der bipolaren Depression ist bei bisher unzureichender Datenlage umstritten. Zunächst sollte bei depressiven Episoden eine Phasenprophylaxe begonnen oder eine bestehende Phasenprophylaxe optimiert und bei stärkerer Ausprägung mit einer der genannten antidepressiv wirksamen Substanzen behandelt werden. Bei Nonresponse kann die Kombination von Lithium und Lamotrigin oder die Gabe eines Antidepressivums in Kombination mit Lithium, Antiepileptika oder atypischen Antipsychotika notwendig sein. Bei depressiven Episoden unter bestehender Phasenprophylaxe sind Kombinationsbehandlungen der verschiedenen Substanzen, teilweise auch mit Antidepressiva, notwendig. Bei Therapieresistenz der depressiven Episode sind komplexere Behandlungsstrategien (z. B. Kombinationstherapien, MAO-Hemmer) zu berücksichtigen.

Summary

Treatment of bipolar depression requires complex treatment decisions in daily routine care. The best evidence for pharmacological treatment is given for quetiapine and with limitations also in off-label use for lamotrigine, especially in combination with lithium, carbamazepine and olanzapine. Effectiveness and recommendation of antidepressants in treatment of bipolar depression remain controversial because of insufficient data. Initially, in depressive episodes a phase prophylactic treatment should be initiated or (if already existing) optimized and more severe episodes should be treated with the substances described before. In case of non-response, the combination of lithium and lamotrigine or antidepressants in combination with lithium, antiepileptics or atypical antipsychotics may be necessary. If depressive episodes occur in the course of pharmacological treatment with prophylactic agents, combination therapies of different substances, even with antidepressants, are necessary. In case of treatment-resistant depressive episodes, complex treatment strategies (e.g. combination therapies and MAO inhibitors) should be considered.

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Literatur

  1. Amsterdam JD, Shults J (2008) Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II major depressive episode: a randomized open-label study. J Clin Psychopharmacol 28:171–181

    Article  CAS  PubMed  Google Scholar 

  2. Angst J, Cui L, Swendsen J et al (2010) Major depressive disorder with subthreshold bipolarity in the National Comorbidity Survey Replication. Am J Psychiatry 167:1194–1201

    Article  PubMed Central  PubMed  Google Scholar 

  3. Baldessarini RJ, Vieta E, Calabrese JR et al (2010) Bipolar depression: overview and commentary. Harv Rev Psychiatry 18:143–157

    Article  PubMed  Google Scholar 

  4. Bauer M, Ritter P, Grunze H et al (2012) Treatment options for acute depression in bipolar disorder. Bipolar Disord 14(Suppl 2):37–50

    Article  PubMed  Google Scholar 

  5. Berk M, Dean O, Cotton SM et al (2011) The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 135:389–394

    Article  CAS  PubMed  Google Scholar 

  6. Bond DJ, Lam RW, Yatham LN (2010) Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis. J Affect Disord 124:228–234

    Article  CAS  PubMed  Google Scholar 

  7. Bottlender R, Rudolf D, Strauss A et al (2001) Mood-stabilisers reduce the risk of developing antidepressant-induced maniform states in acute treatment of bipolar I depressed patients. J Affect Disord 63:79–83

    Article  CAS  PubMed  Google Scholar 

  8. Bowden CL, Calabrese JR, McEroy SL et al (2000) A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group. Arch Gen Psychiatry 57:481–489

    Article  CAS  PubMed  Google Scholar 

  9. Bschor T (2008) Therapieresistente bipolare Depressionen. In: Bschor T (Hrsg) Behandlungsmanual therapieresistente Depression. Kohlhammer, Stuttgart, S 165–182

  10. Bschor T, Angst J, Azorin JM et al (2012) Are bipolar disorders underdiagnosed in patients with depressive episodes? Results of the multicenter BRIDGE screening study in Germany. J Affect Disord 142:45–52

    Article  CAS  PubMed  Google Scholar 

  11. Calabrese JR, Bowden CL, Sachs GS et al (1999) A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry 60:79–88

    Article  CAS  PubMed  Google Scholar 

  12. Calabrese JR, Keck PE Jr, Macfadden W et al (2005) A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 162:1351–1360

    Article  PubMed  Google Scholar 

  13. Calabrese JR, Ketter TA, Youakim JM et al (2010) Adjunctive armodafinil for major depressive episodes associated with bipolar I disorder: a randomized, multicenter, double-blind, placebo-controlled, proof-of-concept study. J Clin Psychiatry 71:1363–1370

    Article  CAS  PubMed  Google Scholar 

  14. Chengappa KN, Levine J, Gershon S et al (2000) Inositol as an add-on treatment for bipolar depression. Bipolar Disord 2:47–55

    Article  CAS  PubMed  Google Scholar 

  15. Cipriani A, Pretty H, Hawton K et al (2005) Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry 162:1805–1819

    Article  PubMed  Google Scholar 

  16. Cohn JB, Collins G, Ashbrook E et al (1989) A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder. Int Clin Psychopharmacol 4:313–322

    Article  CAS  PubMed  Google Scholar 

  17. Colom F, Vieta E, Daban C et al (2006) Clinical and therapeutic implications of predominant polarity in bipolar disorder. J Affect Disord 93:13–17

    Article  CAS  PubMed  Google Scholar 

  18. Cruz N, Sanchez-Moreno J, Torres F et al (2010) Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. Int J Neuropsychopharmacol 13:5–14

    Article  CAS  PubMed  Google Scholar 

  19. Davis LL, Bartolucci A, Petty F (2005) Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord 85:259–266

    Article  CAS  PubMed  Google Scholar 

  20. DGBS, DGPPN (2012) S3-Leitlinie zur Diagnostik und Therapie Bipolarer Störungen. Langversion 2012

  21. El-Mallakh RS, Salem MR, Chopra A et al (2010) A blinded, randomized comparison of immediate-release and extended-release carbamazepine capsules in manic and depressed bipolar subjects. Ann Clin Psychiatry 22:3–8

    PubMed  Google Scholar 

  22. Forty L, Smith D, Jones L et al (2008) Clinical differences between bipolar and unipolar depression. Br J Psychiatry 192:388–389

    Article  PubMed  Google Scholar 

  23. Frye MA (2011) Clinical practice. Bipolar disorder – a focus on depression. N Engl J Med 364:51–59

    Article  CAS  PubMed  Google Scholar 

  24. Frye MA, Grunze H, Suppes T et al (2007) A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry 164:1242–1249

    Article  PubMed  Google Scholar 

  25. Furey ML, Drevets WC (2006) Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry 63:1121–1129

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Geddes JR, Calabrese JR, Goodwin GM (2009) Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry 194:4–9

    Article  PubMed  Google Scholar 

  27. Geddes JR, Goodwin GM, Rendell J et al (2010) Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet 375:385–395

    Article  PubMed  Google Scholar 

  28. Ghaemi SN, Gilmer WS, Goldberg JF et al (2007) Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study. J Clin Psychiatry 68:1840–1844

    Article  CAS  PubMed  Google Scholar 

  29. Goldberg JF, Burdick KE, Endick CJ (2004) Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 161:564–566

    Article  PubMed  Google Scholar 

  30. Grunze H, Vieta E, Goodwin GM et al (2010) The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2010 on the treatment of acute bipolar depression. World J Biol Psychiatry 11:81–109

    Article  PubMed  Google Scholar 

  31. Loebel A, Cucchiaro J, Silva R (2012) Lurasidone adjunctive to lithium or valproate for the treatment of bipolar I depression: results of a 6-week, double-blind, placebo-controlled. American Psychiatric Association, Philadelphia, Abstract NR3-72

  32. Loebel A, Cucchiaro J, Silva R (2012) Lurasidone monotherapy for the treatment of bipolar I depression: results of a 6-week, double-blind, placebo-controlled study. American Psychiatric Association, Philadelphia

  33. Macritchie K, Geddes JR, Scott J et al (2003) Valproate for acute mood episodes in bipolar disorder. Cochrane Database Syst Rev CD004052

  34. Mcelroy SL, Weisler RH, Chang W et al (2010) A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II). J Clin Psychiatry 71:163–174

    Article  CAS  PubMed  Google Scholar 

  35. NCCMH (2006) Bipolar disorder: the management of bipolar disorder in adults, children and adolescents, in primary and secondary care. The British Psychological Society and the Royal College of Psychiatrists, Leicester and London

  36. Novick DM, Swartz HA, Frank E (2010) Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence. Bipolar Disord 12:1–9

    Article  PubMed  Google Scholar 

  37. Perlis RH, Dennehy EB, Miklowitz DJ et al (2009) Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study. Bipolar Disord 11:391–400

    Article  PubMed Central  PubMed  Google Scholar 

  38. Sachs GS, Ice KS, Chappell PB et al (2011) Efficacy and safety of adjunctive oral ziprasidone for acute treatment of depression in patients with bipolar I disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 72:1413–1422

    Article  CAS  PubMed  Google Scholar 

  39. Sachs GS, Nierenberg AA, Calabrese JR et al (2007) Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 356:1711–1722

    Article  CAS  PubMed  Google Scholar 

  40. Sidor MM, Macqueen GM (2011) Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry 72:156–167

    Article  CAS  PubMed  Google Scholar 

  41. Smith LA, Cornelius VR, Azorin JM et al (2010) Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. J Affect Disord 122:1–9

    Article  CAS  PubMed  Google Scholar 

  42. Suppes T, Marangell LB, Bernstein IH et al (2008) A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression. J Affect Disord 111:334–343

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Thase ME, Jonas A, Khan A et al (2008) Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. J Clin Psychopharmacol 28:13–20

    Article  CAS  PubMed  Google Scholar 

  44. Thase ME, Macfadden W, Weisler RH et al (2006) Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 26:600–609

    Article  CAS  PubMed  Google Scholar 

  45. Tohen M, Mcdonnell DP, Case M et al (2012) Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression. Br J Psychiatry 201:376–382

    Article  PubMed  Google Scholar 

  46. Tohen M, Vieta E, Calabrese J et al (2003) Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 60:1079–1088

    Article  CAS  PubMed  Google Scholar 

  47. Tondo L, Baldessarini RJ, Vazquez G et al (2013) Clinical responses to antidepressants among 1036 acutely depressed patients with bipolar or unipolar major affective disorders. Acta Psychiatr Scand 127:355–364

    Article  CAS  PubMed  Google Scholar 

  48. Tondo L, Vazquez G, Baldessarini RJ (2010) Mania associated with antidepressant treatment: comprehensive meta-analytic review. Acta Psychiatr Scand 121:404–414

    Article  CAS  PubMed  Google Scholar 

  49. Vazquez G, Tondo L, Baldessarini RJ (2011) Comparison of antidepressant responses in patients with bipolar vs. unipolar depression: a meta-analytic review. Pharmacopsychiatry 44:21–26

    CAS  PubMed  Google Scholar 

  50. Vazquez GH, Tondo L, Undurraga J et al (2013) Overview of antidepressant treatment of bipolar depression. Int J Neuropsychopharmacol 16:1673–1685

    Article  CAS  PubMed  Google Scholar 

  51. Yatham LN, Kennedy SH, Parikh SV et al (2013) 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 15:1–44

    Article  CAS  PubMed  Google Scholar 

  52. Zarate CA Jr, Brutsche NE, Ibrahim L et al (2012) Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 71:939–946

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Zarate CA Jr, Payne JL, Singh J et al (2004) Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 56:54–60

    Article  CAS  PubMed  Google Scholar 

  54. Zarate CA Jr, Quiroz JA, Singh JB et al (2005) An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry 57:430–432

    Article  CAS  PubMed  Google Scholar 

  55. Zhang ZJ, Kang WH, Tan QR et al (2007) Adjunctive herbal medicine with carbamazepine for bipolar disorders: A double-blind, randomized, placebo-controlled study. J Psychiatr Res 41:360–369

    Article  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. S. Köhler gibt an, dass kein Interessenkonflikt besteht. M. Bauer: Forschungszuwendungen: Stanley Medical Research Institute, European Commission (FP7), National Alliance for Research on Schizophrenia and Depression (NARSAD), Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), American Foundation of Suicide Prevention; Beratertätigkeit: Alkermes, AstraZeneca, BristolMyers Squibb, Ferrer Internacional, Janssen, Lilly, Lundbeck, Otsuka, Servier, Takeda; Vertragshonorare: AstraZeneca, BristolMyers Squibb, Ferrer Internacional, Lilly, Lundbeck, Servier, Otsuka. T. Bschor hat in den letzten 5 Jahren Vortragshonorare der Firmen Lilly, esparma, BMS, Servier, AstraZeneca und Lundbeck sowie Kongressreiseunterstützung der Firmen AstraZeneca und Lundbeck angenommen. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik für Psychiatrie und Psychotherapie, Charité – Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117, Berlin, Deutschland

    S. Köhler

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland

    M. Bauer & T. Bschor

  3. Abteilung für Psychiatrie, Schlosspark-Klinik, Berlin, Deutschland

    T. Bschor

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  1. S. Köhler
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Correspondence to S. Köhler.

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Köhler, S., Bauer, M. & Bschor, T. Pharmakologische Behandlung der bipolaren Depression. Nervenarzt 85, 1075–1083 (2014). https://doi.org/10.1007/s00115-013-3919-0

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