Download PDF
Pharmacopsychiatry 2014; 47(02): 53-59
DOI: 10.1055/s-0033-1364004
Review
© Georg Thieme Verlag KG Stuttgart · New York

The Challenge of Treatment in Bipolar Depression: Evidence from Clinical Guidelines, Treatment Recommendations and Complex Treatment Situations

S. Köhler
1   Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany
,
S. Gaus
1   Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany
,
T. Bschor
2   Department of Psychiatry, Schlosspark-Klinik, Berlin, Germany
3   Department of Psychiatry and Psychotherapy, University Hospital Dresden, Dresden, Germany
› Author Affiliations
Further Information

Publication History

received 14 September 2013
revised 09 December 2013

accepted 18 December 2013

Publication Date:
18 February 2014 (online)

Also available at
   Permissions and Reprints

Abstract

Bipolar depression and its clinical presentation is a frequent but complex psychiatric disease. Despite the high prevalence and the clinical and economic relevance of bipolar depression, few treatments are proven to be highly and consistently effective. In practice, the treatment of bipolar depression typically includes complex treatment decision-making. The best evidence for a pharmacological treatment exists for quetiapine. Alternatives with limitations are lamotrigine (also in the combination with lithium), carbamazepine and olanzapine. The effectiveness and recommendation of antidepressants in the treatment of bipolar depression remains controversial. Initially, depressive episodes should been treated with one of the named substances with antidepressant properties. In non-responders, a combination of lithium and lamotrigine, or antidepressants in combination with either lithium, an antiepileptic drug or atypical antipsychotics, may be necessary. If a depressive episode occurs under ongoing mood-stabilizing treatment, combination treatments of different substances, even with antidepressants, can be necessary. In the case of treatment-resistant depressive episodes, complex treatment strategies (combination therapies, MAO inhibitors) should be considered. This review describes the treatment recommendations of different guidelines for bipolar depression and emphasizes their differences. Furthermore, alternative pharmacological treatment strategies and complex treatment situations are discussed.

Key words

bipolar disorder treatment - depression treatment - mood disorders
 

  • References

  • 1 Perlis RH, Dennehy EB, Miklowitz DJ et al. Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study. Bipolar Disord 2009; 11: 391-400
    CrossrefPubMedGoogle Scholar
  • 2 Frye MA. Clinical practice. Bipolar disorder – a focus on depression. N Engl J Med 2011; 364: 51-59
    CrossrefPubMedGoogle Scholar
  • 3 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
  • 4 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
  • 5 Novick DM, Swartz HA, Frank E. Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence. Bipolar Disord 2010; 12: 1-9
    PubMedGoogle Scholar
  • 6 Forty L, Smith D, Jones L et al. Clinical differences between bipolar and unipolar depression. Br J Psychiatry 2008; 192: 388-389
    CrossrefPubMedGoogle Scholar
  • 7 Baldessarini RJ, Vieta E, Calabrese JR et al. Bipolar depression: overview and commentary. Harv Rev Psychiatry 2010; 18: 143-157
    CrossrefPubMedGoogle Scholar
  • 8 Pezawas L, Angst J, Kasper S. Recurrent brief depression revisited. Int Rev Psychiatry 2005; 17: 63-70
    CrossrefPubMedGoogle Scholar
  • 9 Colom F, Vieta E, Daban C et al. Clinical and therapeutic implications of predominant polarity in bipolar disorder. J Affect Disord 2006; 93: 13-17
    CrossrefPubMedGoogle Scholar
  • 10 DGBS, DGPPN. S3-Leitlinie zur Diagnostik und Therapie Bipolarer Störungen. Langversion 2012.: www.leitlinie-bipolar.de 2012
    PubMedGoogle Scholar
  • 11 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: 1-44
    PubMedGoogle Scholar
  • 12 NCCMH . Bipolar Disorder: the Management of Bipolar Disorder in Adults, Children and Adolescents, in Primary and Secondary Care. Leicester and London: The British Psychological Society and the Royal College of Psychiatrists; 2006
    Google Scholar
  • 13 Grunze H, Vieta E, Goodwin GM et al. 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 2010; 11: 81-109
    CrossrefPubMedGoogle Scholar
  • 14 Bauer M, Ritter P, Grunze H et al. Treatment options for acute depression in bipolar disorder. Bipolar Disord 2012; 14 (Suppl. 02) 37-50
    CrossrefPubMedGoogle Scholar
  • 15 Cohn JB, Collins G, Ashbrook E et al. A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder. Int Clin Psychopharmacol 1989; 4: 313-322
    CrossrefPubMedGoogle Scholar
  • 16 Amsterdam JD, Shults J. Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II major depressive episode: a randomized open-label study. J Clin Psychopharmacol 2008; 28: 171-181
    CrossrefPubMedGoogle Scholar
  • 17 McElroy SL, Weisler RH, Chang W et al. A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II). J Clin Psychiatry 2010; 71: 163-174
    CrossrefPubMedGoogle Scholar
  • 18 Sachs GS, Nierenberg AA, Calabrese JR et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007; 356: 1711-1722
    CrossrefPubMedGoogle Scholar
  • 19 Tohen M, Vieta E, Calabrese J et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003; 60: 1079-1088
    CrossrefPubMedGoogle Scholar
  • 20 Nemeroff CB, Evans DL, Gyulai L et al. Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry 2001; 158: 906-912
    CrossrefPubMedGoogle Scholar
  • 21 Sidor MM, Macqueen GM. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry 2011; 72: 156-167
    CrossrefPubMedGoogle Scholar
  • 22 Vazquez G, Tondo L, Baldessarini RJ. Comparison of antidepressant responses in patients with bipolar vs. unipolar depression: a meta-analytic review. Pharmacopsychiatry 2011; 44: 21-26
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Tondo L, Baldessarini RJ, Vazquez G et al. Clinical responses to antidepressants among 1 036 acutely depressed patients with bipolar or unipolar major affective disorders. Acta Psychiatr Scand 2013; 127: 355-364
    CrossrefPubMedGoogle Scholar
  • 24 Vazquez GH, Tondo L, Undurraga J et al. Overview of antidepressant treatment of bipolar depression. Int J Neuropsychopharmacol 2013; 16: 1673-1685
    CrossrefPubMedGoogle Scholar
  • 25 Tondo L, Vazquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Acta Psychiatr Scand 2010; 121: 404-414
    CrossrefPubMedGoogle Scholar
  • 26 Bottlender R, Rudolf D, Strauss A et al. Mood-stabilisers reduce the risk of developing antidepressant-induced maniform states in acute treatment of bipolar I depressed patients. J Affect Disord 2001; 63: 79-83
    CrossrefPubMedGoogle Scholar
  • 27 Young AH, McElroy SL, Bauer M et al. A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I). J Clin Psychiatry 2010; 71: 150-162
    CrossrefPubMedGoogle Scholar
  • 28 Suppes T, Marangell LB, Bernstein IH et al. A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression. J Affect Disord 2008; 111: 334-343
    CrossrefPubMedGoogle Scholar
  • 29 Cipriani A, Pretty H, Hawton K et al. 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 2005; 162: 1805-1819
    CrossrefPubMedGoogle Scholar
  • 30 Calabrese JR, Bowden CL, Sachs GS et al. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry 1999; 60: 79-88
    CrossrefPubMedGoogle Scholar
  • 31 Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry 2009; 194: 4-9
    CrossrefPubMedGoogle Scholar
  • 32 Macritchie K, Geddes JR, Scott J et al. Valproate for acute mood episodes in bipolar disorder. Cochrane Database Syst Rev 2003; DOI: 10.1002/14651858. CD004052: CD004052
    PubMedGoogle Scholar
  • 33 Geddes JR, Goodwin GM, Rendell J et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet 2010; 375: 385-395
    CrossrefPubMedGoogle Scholar
  • 34 Bowden CL, Calabrese JR, McElroy SL et al. 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 2000; 57: 481-489
    CrossrefPubMedGoogle Scholar
  • 35 Davis LL, Bartolucci A, Petty F. Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord 2005; 85: 259-266
    CrossrefPubMedGoogle Scholar
  • 36 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
  • 37 Bond DJ, Lam RW, Yatham LN. Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis. J Affect Disord 2010; 124: 228-234
    CrossrefPubMedGoogle Scholar
  • 38 Smith LA, Cornelius VR, Azorin JM et al. Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. J Affect Disord 2010; 122: 1-9
    CrossrefPubMedGoogle Scholar
  • 39 Zhang ZJ, Kang WH, Tan QR et al. Adjunctive herbal medicine with carbamazepine for bipolar disorders: A double-blind, randomized, placebo-controlled study. J Psychiatr Res 2007; 41: 360-369
    CrossrefPubMedGoogle Scholar
  • 40 El-Mallakh RS, Salem MR, Chopra A et al. A blinded, randomized comparison of immediate-release and extended-release carbamazepine capsules in manic and depressed bipolar subjects. Ann Clin Psychiatry 2010; 22: 3-8
    PubMedGoogle Scholar
  • 41 Cruz N, Sanchez-Moreno J, Torres F et al. Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. Int J Neuropsychopharmacol 2010; 13: 5-14
    CrossrefPubMedGoogle Scholar
  • 42 Calabrese JR, Keck Jr PE, 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: 1351-1360
    CrossrefPubMedGoogle Scholar
  • 43 Thase ME, Macfadden W, Weisler RH et al. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 2006; 26: 600-609
    CrossrefPubMedGoogle Scholar
  • 44 Tohen M, McDonnell DP, Case M et al. Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression. Br J Psychiatry 2012; 201: 376-382
    CrossrefPubMedGoogle Scholar
  • 45 Thase ME, Jonas A, Khan A et al. Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. J Clin Psychopharmacol 2008; 28: 13-20
    CrossrefPubMedGoogle Scholar
  • 46 Sachs GS, Ice KS, Chappell PB et al. 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 2011; 72: 1413-1422
    CrossrefPubMedGoogle Scholar
  • 47 Loebel A, Cucchiaro J, Silva R. Lurasidone Monotherapy for the Treatment of Bipolar I Depression: Results of a 6-Week, Double-Blind, Placebo-Controlled Study. American Psychiatric Association; Philadelphia, PA: 2012
    Google Scholar
  • 48 Loebel A, Cucchiaro J, Silva R. 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, PA: 2012
    Google Scholar
  • 49 Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 2004; 161: 564-566
    CrossrefPubMedGoogle Scholar
  • 50 Zarate Jr CA, Payne JL, Singh J et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 2004; 56: 54-60
    CrossrefPubMedGoogle Scholar
  • 51 Chengappa KN, Levine J, Gershon S et al. Inositol as an add-on treatment for bipolar depression. Bipolar Disord 2000; 2: 47-55
    CrossrefPubMedGoogle Scholar
  • 52 Frye MA, Grunze H, Suppes T et al. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry 2007; 164: 1242-1249
    CrossrefPubMedGoogle Scholar
  • 53 Calabrese JR, Ketter TA, Youakim JM et al. 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 2010; 71: 1363-1370
    CrossrefPubMedGoogle Scholar
  • 54 Zarate Jr CA, Brutsche NE, Ibrahim L et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 2012; 71: 939-946
    CrossrefPubMedGoogle Scholar
  • 55 Furey ML, Drevets WC. Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry 2006; 63: 1121-1129
    CrossrefPubMedGoogle Scholar
  • 56 Zarate Jr CA, Quiroz JA, Singh JB et al. An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry 2005; 57: 430-432
    CrossrefPubMedGoogle Scholar
  • 57 Berk M, Dean O, Cotton SM et al. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 2011; 135: 389-394
    CrossrefPubMedGoogle Scholar
  • 58 Bschor T. Treatment resistant bipolar depression. In: Bschor T. ed. Treatment manual of treatment resistant depression. Stuttgart: Kohlhammer; 2008: 165-182
    Google Scholar
  • 59 Jacobi F, Wittchen HU, Holting C et al. Prevalence, co-morbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS). Psychol Med 2004; 34: 597-611
    Google Scholar
  • 60 Wittchen HU, Jacobi F, Rehm J et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011; 21: 655-679
    Google Scholar
  • 61 Alonso J, Angermeyer MC, Bernert S et al. Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 2004; DOI: 10.1111/j.1600-0047.2004.00327.x. 21-27
    PubMedGoogle Scholar
  • 62 Bauer M, Glenn T, Rasgon N et al. Association between age of onset and mood in bipolar disorder: comparison of subgroups identified by cluster analysis and clinical observation. J Psychiatr Res 2010; 44: 1170-1175
    CrossrefPubMedGoogle Scholar
  • 63 Baldessarini RJ, Tondo L, Hennen J. Treatment-latency and previous episodes: relationships to pretreatment morbidity and response to maintenance treatment in bipolar I and II disorders. Bipolar Disord 2003; 5: 169-179
    CrossrefPubMedGoogle Scholar
  • 64 Judd LL, Akiskal HS, Schettler PJ et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002; 59: 530-537
    CrossrefPubMedGoogle Scholar
  • 65 Goodwin FK. Manic-depressive illness: bipolar disorders and recurrent depression. New York: Oxford University Press; 2007
    Google Scholar
  • 66 Chen YW, Dilsaver SC. Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol Psychiatry 1996; 39: 896-899
    CrossrefPubMedGoogle Scholar