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A systematic review of the evidence for the treatment of acute depression in bipolar I disorder

Published online by Cambridge University Press:  18 March 2013

Michael A. Cerullo*
Affiliation:
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, USA
Stephen M. Strakowski
Affiliation:
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, USA
*
*Address for correspondence: Michael Cerullo, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati COM, 260 Stetson Street, Suite 3200, Cincinnati, OH 45219-0516, USA. Email Michael.Cerullo@uc.edu)

Abstract

In this article, we examined evidence for the acute treatment of depression in bipolar I disorder, focusing on double-blind, placebo-controlled studies with a definite primary outcome measure and published in peer review journals. Quetiapine and olanzapine/fluoxetine are currently approved by the FDA for the treatment of bipolar depression, and a number of additional agents (including other atypical antipsychotics, mood stabilizers, antidepressants, and novel compounds) have been studied with varying degrees of efficacy. The medication with the most evidence for efficacy in bipolar depression is quetiapine, with five studies showing positive efficacy compared to placebo. In contrast, five studies of lamotrigine were negative, although meta-analyses of the pooled have found some treatment effects. Two studies of olanzapine and olanzapine/fluoxetine and three small studies of divalproex showed significant efficacy in treating bipolar depression. Two studies of aripiprazole found no differences compared to placebo. Early research on lithium in bipolar depression had significant methodological flaws, and only one study of lithium met our primary search criteria. To better understand the role of antidepressants, we also examined studies of antidepressants as adjunctive treatment of bipolar depression in participants taking mood stabilizers or atypical antipsychotics. These studies reported mixed results for a variety of antidepressants, but the majority found no differences compared to placebo. Other studies of adjunctive treatment were also discussed. There has been one positive adjunctive study each of lamotrigine, omega-3 fatty acids, modafinil, and armodafinil, while there was one negative trial each of omega-3 fatty acids, ziprasidone, and levetiracetam.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2013 

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References

1.Narrow, W, Rae, D, Robins, L, etal. Revised prevalence estimates of mental disorders in the United States: using a clinical significance criterion to reconcile 2 surveys’ estimates. Arch Gen Psychiatry. 2002; 59: 115123.CrossRefGoogle ScholarPubMed
2.Judd, L, Akiskal, H. The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthreshold cases. J Affect Disord. 2003; 73: 123131.CrossRefGoogle ScholarPubMed
3.Zornberg, G, Pope, H. Treatment of depression in bipolar disorder: new directions for research. J Clin Psychopharmacol. 1993; 13(6): 397408.CrossRefGoogle ScholarPubMed
4.Van Lieshout, RJ, MacQueen, GM. Efficacy and acceptability of mood stabilizers in the treatment of acute bipolar depression: systematic review. Br J Psychiatry. 2010; 196: 266273.CrossRefGoogle ScholarPubMed
5.Nivoli, AM, Colom, F, Murru, A, etal. New treatment guidelines for acute bipolar depression: a systematic review. J Affect Disord. 2011; 129: 1426.CrossRefGoogle ScholarPubMed
6.Vieta, E, Locklear, J, Gunther, O, etal. Treatment options for bipolar depression: a systematic review of randomized, controlled trials. J Clin Psychopharmacol. 2010; 30(5): 579590.CrossRefGoogle ScholarPubMed
7.Geddes, JR, Calabrese, JR, Goodwin, GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomized trials. Br J Psychiatry. 2009; 194: 49.CrossRefGoogle Scholar
8.De Fruyt, F, Deschepper, E, Audenaert, K, etal. Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis. J Psychopharmacol. 2011; 26(5): 603617.CrossRefGoogle ScholarPubMed
9.Smith, LA, Cornelius, VR, Azorin, JM, etal. Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. J Affect Disord. 2010; 122: 19.CrossRefGoogle ScholarPubMed
10.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: 228234.CrossRefGoogle ScholarPubMed
11.Fountoulakis, KN, Grunze, H, Panagiotidis, P, Kaprinis, G. Treatment of bipolar depression: an update. J Affect Disord. 2008; 109: 2134.CrossRefGoogle ScholarPubMed
12.Dodd, BM. Bipolar II disorder: a review. Bipolar Disord. 2005; 7: 1121.Google Scholar
13.Sidor, MM, MacQueen, GM. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry. 2011; 72(2): 156167.CrossRefGoogle ScholarPubMed
14.Gijsman, H, Geddes, J, Rendell, J, Nolen, W, Goodwin, G. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004; 161(9): 15371547.CrossRefGoogle ScholarPubMed
15.Spanemberg, L, Massuda, R, Lovato, L, etal. Pharmacological treatment of bipolar depression: qualitative systematic review of double-blind randomized clinical trials. Psychiatr Q. 2012; 83: 161175.CrossRefGoogle ScholarPubMed
16.Calabrese, JR, Keck, PE, Macfadden, W, etal. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005; 162(7): 13511360.CrossRefGoogle ScholarPubMed
17.Thase, ME, Macfadden, W, Weisler, RH, etal. Efficacy of quetiapine monotherapy in bipolar I and II depression. J Clin Psychopharmacol. 2006; 26(6): 600609.CrossRefGoogle ScholarPubMed
18.McElroy, S, Weisler, R, Chang, W, etal. A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II). J Clin Psychiatry. 2010; 71(2): 163174.CrossRefGoogle ScholarPubMed
19.Suppes, T, Datto, C, Minkwitz, M, etal. Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord. 2010; 121: 106115.CrossRefGoogle ScholarPubMed
20.Young, AH, FRCPsych McElroy, SL, etal. 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(2): 150162.CrossRefGoogle ScholarPubMed
21.Tohen, M, Vieta, E, Calabrese, J, etal. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry. 2003; 60: 10791088.CrossRefGoogle ScholarPubMed
22.Tohen, M, McDonnell, DP, Case, M, etal. Randomized, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression. Br J Psychiatry. In press. DOI: 10.1192/bjp.bp.112.108357.Google Scholar
23.Thase, ME, Jonas, A, Khan, A, etal. Aripiprazole monotherapy in non-psychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. J Clin Psychopharmacol. 2008; 28(1): 1320.CrossRefGoogle Scholar
24.Lombardo, L, Sachs, G, Kolluri, S, Kremer, C, Yang, R. Two 6-week, randomized, double-blind, placebo-controlled studies of ziprasidone in outpatients with bipolar I depression. J Clin Psychopharmacol. 2012; 32(4): 470478.CrossRefGoogle ScholarPubMed
25.Sachs, GS, Ice, KS, Chappell, PB. 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(10): 14131422.CrossRefGoogle ScholarPubMed
26.Calabrese, JR, Huffman, RF, White, RL, etal. Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials. Bipolar Disord. 2008; 10: 323333.CrossRefGoogle ScholarPubMed
27.Calabrese, JR, Bowden, CL, Sachs, GS, etal. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I disorder. J Clin Psychiatry. 1999; 60(2): 7988.CrossRefGoogle Scholar
28.van der Loos, ML, Mulder, PG, Hartong, EG, etal. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry. 2009; 70(2): 223231.CrossRefGoogle ScholarPubMed
29.Brown, EB, McElroy, SL, Keck, PE, etal. A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression. J Clin Psychiatry. 206; 67: 10251033.CrossRefGoogle Scholar
30.Davis, LL, Bartolucci, A, Petty, F. Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord. 2005; 85: 259266.CrossRefGoogle ScholarPubMed
31.Ghaemi, SN, Gilmer, WS, Goldberg, JF, etal. Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study. J Clin Psychiatry. 2007; 68(12): 18401844.CrossRefGoogle ScholarPubMed
32.Muzina, DJ, Gao, K, Kemp, DE. Acute efficacy of divalproex sodium versus placebo in mood stabilizer-naïve bipolar I or II depression: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2011; 72(6): 813819.CrossRefGoogle ScholarPubMed
33.Baron, MB, Gershon, ES, Rudy, V, etal. Lithium carbonate response in depression. Arch Gen Psychiatry. 1975; 32: 11071111.CrossRefGoogle ScholarPubMed
34.Goodwin, FK, Murphy, DL, Bunney, WE. Lithium-carbonate treatment in depression and mania. Arch Gen Psychiatry. 1969; 21: 486496.CrossRefGoogle ScholarPubMed
35.Noyes, R, Dempsey, GM, Blum, A, Cavanaugh, GL. Lithium treatment of depression. Compr Psychiatry. 1974; 15(3): 187193.CrossRefGoogle ScholarPubMed
36.Stokes, PE, Stoll, PM, Shamoian, CA, Patton, MJ. Efficacy of lithium as acute treatment of manic-depressive illness. Lancet. 1971; 1: 13191325.CrossRefGoogle ScholarPubMed
37.Goodwin, FK, Murphy, DL, Dunner, DL, Bunney, WE. Lithium response in unipolar versus bipolar depression. Am J Psychiatry. 1972; 129(1): 7679.CrossRefGoogle ScholarPubMed
38.Cohn, JB, Collins, G, Ashbrook, E, Wernicke, JF. A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder. Int Clin Psychopharmacol. 1989; 4: 313322.CrossRefGoogle ScholarPubMed
39.Nemeroff, CB, Evans, DL, Gyulai, L, etal. Double-blind, placebo controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry. 2001; 158(6): 906912.CrossRefGoogle ScholarPubMed
40.Sachs, GS, Nierenberg, AA, Calabrese, JR, etal. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007; 356(17): 17111722.CrossRefGoogle ScholarPubMed
41.Calabrese, JR, Ketter, TA, Youakim, JM, etal. 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(10): 13631370.CrossRefGoogle ScholarPubMed
42.Saricicek, A, Maloney, K, Muralidharan, A, etal. Levetiracetam in the management of bipolar depression: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011; 72(6): 744750.CrossRefGoogle ScholarPubMed
43.Ghaemi, SN, Goodwin, FK. Antidepressants for bipolar depression. Am J Psychiatry. 2005; 162(8): 15451546.CrossRefGoogle ScholarPubMed
44.Goldberg, JF, Truman, CJ. Antidepressant-induced mania: an overview of current controversies. Bipolar Disord. 2003; 5: 407420.CrossRefGoogle ScholarPubMed
45.Tondo, L, Vazquez, G, Baldessarini, RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Acta Psychiatr Scand. 2010; 121: 404414.CrossRefGoogle ScholarPubMed
46.Licht, RW, Gijsman, H, Nolen, WA, Angst, J. Are antidepressants safe in the treatment of bipolar depression? A critical evaluation of their potential risk to induce switch into mania or cycle acceleration. Acta Psychiatr Scand. 2008; 118: 337346.CrossRefGoogle ScholarPubMed
47.Frye, MA, Grunze, H, Suppes, T, etal. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry. 2007; 164: 12421249.CrossRefGoogle ScholarPubMed
48.Stoll, AL, Severus, WE, Freeman, MP, etal. Omega 3 fatty acids in bipolar disorder. Arch Gen Psychiatry. 1999; 56: 407412.CrossRefGoogle ScholarPubMed
49.Keck, PE, Mintz, J, McElroy, SL, etal. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry. 2006; 60: 10201022.CrossRefGoogle ScholarPubMed
50.Altshuler, LL, Post, RM, Hellemann, G, etal. Impact of antidepressant continuation after acute positive or partial treatment response for bipolar depression: a blinded randomized study. J Clin Psychiatry. 2009; 70(4): 450457.CrossRefGoogle ScholarPubMed
51.Ghaemi, SN, Ostacher, MM, El-Mallakh, RS, etal. Antidepressant discontinuation in bipolar depression: a systematic treatment enhancement program for bipolar disorder (STEP-BP) randomized clinical trial of long-term effectiveness and safety. J Clin Psychiatry. 2010; 71(4): 372380.CrossRefGoogle ScholarPubMed