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DOI: 10.1055/s-0030-1265198
© Georg Thieme Verlag KG Stuttgart · New York
Comparison of Antidepressant Responses in Patients with Bipolar vs. Unipolar Depression: A Meta-Analytic Review
Publication History
received 02.06.2010
revised 03.08.2010
accepted 09.08.2010
Publication Date:
28 October 2010 (online)
![](https://www.thieme-connect.de/media/pharmaco/201101/lookinside/thumbnails/10.1055-s-0030-1265198-1.jpg)
Abstract
Background: Since there is considerable uncertainty about therapeutic responses to antidepressants among depressed patients diagnosed with bipolar (BP) vs. unipolar (UP) mood disorders, we have reviewed available studies that compared both types of depressed patients.
Methods: Extensive computerized literature-searching identified reports of antidepressant studies involving both BP and UP depressed patients. We used random-effects meta-analysis to compare short-term drug responses by patient type, as well as meta-regression modeling for effects of selected covariates.
Results: We identified only 10 studies meeting even liberal inclusion criteria, and they varied greatly in size and design quality. The overall difference in antidepressant responses between BP (n=863) and UP (n=2 226) disorder patients was not significant (pooled RR=1.05; CI: 0.96–1.15; p=0.34). Based on meta-regression, we also found no difference in responses based on diagnosis or subtype, subjects/study, % women, average age, or length of treatment based on meta-regression. Risk of manic-switching averaged 2.50 vs. 0.275%/week among BP vs. UP disorder patients, including co-treatment with mood stabilizers in 70% of BP patients.
Comments: The findings suggest little difference in antidepressant responses by diagnostic type, sex, or other factors considered, but a substantial risk of mania and hypomania with BP disorders. However, data pertaining to the fundamental question of antidepressant response among BP vs. UP depressed patients were strikingly limited, and support only tentative conclusions. Additional, well-designed, prospective trials of matched BP and UP depression patients and controlled treatment are required.
References
- 1 Smith DJ, Forty L, Russell E. et al . Sub-threshold manic symptoms in recurrent major depressive disorder are a marker for poor outcome. Acta Psychiatr Scand. 2009; 119 325-329
- 2 Kiejna A, Pawłowski T, Dudek D. et al . Utility of the Mood Disorder Questionnaire for the detection of bipolar diathesis in treatment-resistant depression. J Affect Disord. 2010 Jan 6; [Epub ahead of print]
- 3 Baldessarini RJ, Vieta E, Calabrese JR. et al . Bipolar depression: overview and commentary. Harv Rev Psychiatry. 2010; 18 143-157
- 4 Post RM, Leverich GS, Nolen WA. et al . A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network. Bipolar Disord. 2003; 5 396-406
- 5 Goodwin FK, Jamison KR. Manic-Depressive Illness, second edition. New York: Oxford University Press; 2007
- 6 Tondo L, Vázquez G, Baldessarini RJ. Mania associated with antidepressant-treatment: comprehensive meta-analytic review. Acta Psychiatr Scand. 2010; 121 404-414
- 7 Centorrino F, Ventriglio A, Vincenti A. et al . Changes in medication practices for hospitalized psychiatric patients: 2009 versus 2004. Hum Psychopharmacol. 2010; 25 179-186
- 8 Ghaemi SN, Ko JY, Goodwin FK. “Cade's disease” and beyond: misdiagnosis, antidepressant use, and a proposed definition for bipolar spectrum disorder. Can J Psychiatry. 2002; 47 125-134
- 9 Berk M, Dodd S. Are treatment emergent suicidality and decreased response to antidepressants in younger patients due to bipolar disorder being misdiagnosed as unipolar depression?. Med Hypotheses. 2005; 65 39-43
- 10 Sharma V, Khan M, Smith A. A closer look at treatment resistant depression: is it due to a bipolar diathesis?. J Affect Disord. 2005; 84 251-277
- 11 Gijsman H, Geddes J, Rendell J. et al . Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004; 161 1537-1547
- 12 Sachs G, Nierenberg A, Calabrese J. et al . Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007; 26 1711-1722
- 13 Ghaemi SN, Wingo AP, Filkowski MA. et al . Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks. Acta Psychiatr Scand. 2008; 118 347-356
- 14 Altshuler LL, Post RM, Hellemann G. et al . Impact of antidepressant continuation after acute positive or partial treatment response for bipolar depression: a blinded, randomized study. J Clin Psychiatry. 2009; 70 450-457
- 15 Ghaemi SN, Ko JY, Goodwin FK. The bipolar spectrum and the antidepressant view of the world. J Psychiatr Pract. 2001; 7 287-297
- 16 Akiskal HS, Benazzi F, Perugi G. et al . Agitated “unipolar” depression re-conceptualized as depressive mixed state: implications for the antidepressant-suicide controversy. J Affect Disord. 2005; 85 245-258
- 17 Benazzi F. Bipolar disorder – focus on bipolar II disorder and mixed depression. Lancet. 2007; 369 935-945
- 18 Goldberg JF. Antidepressants in bipolar disorder: 7 myths and realities. Curr Psychiatry. 2010; 9 41-51
- 19 PubMed/MEDLINE . Accessible at: http://www.ncbi.nlm.nih.gov/pubmed/ [accessed in May 2010]
- 20 EMBASE . Accessible at: http://www.embase.com/ [accessed in May 2010]
- 21 LILACS . Accessible at: http://bases.bireme.br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&base=LILACS&lang=i&form=F [accessed in May 2010]
- 22 PsiTri . Accessible at: http://psitri.stakes.fi/EN/psitri.htm [accessed in May 2010]
- 23 Google Scholar . Accessible at: http://scholar.google.com/ [accessed in May 2010]
- 24 Gruenberg AM, Goldstein RD, Pincus HA. Classification of depression: research and diagnostic criteria: DSM-IV and ICD-10. Chapt 1 in Licino J, Wong ML, editors. Biology of Depression: From Novel Insights to Therapeutic Strategies. Wenheim, Germany: Wiley-VCH Verlag; 2005: 1-12
- 25 Tondo L, Lepri B, Baldessarini RJ. Responses to antidepressant trials in bipolar I versus unipolar major depression disorder patients. Previously unpublished findings, May. 2010;
- 26 Tondo L, Lepri B, Baldessarini RJ. Responses to antidepressant trials in bipolar II versus unipolar major depression disorder patients. Previously unpublished findings, May. 2010;
- 27 Tondo L, Baldessarini RJ, Lepri B. Age at onset in 3014 bipolar I and II, and recurrent unipolar major depression disorder patients. Acta Psychiatr Scand. 2010; [May 17, Epub ahead of print]
- 28 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986; 7 177-188
- 29 Tsapakis E, Soldani F, Tondo L. et al . Efficacy of antidepressants in depressed children and adolescents: a meta-analysis. Br J Psychiatry. 2008; 193 10-17
- 30 Baldessarini RJ, Tondo L. Meta-analytic comparison of antisuicidal effects of lithium versus anticonvulsants. Pharmacopsychiatry. 2009; 42 72-75
- 31 Amsterdam JD. Efficacy and safety of venlafaxine in bipolar type-II major depressive episode. J Clin Psychopharmacol. 1998; 18 414-417
- 32 Amsterdam JD, Garcia-España F, Fawcett J. et al . Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. J Clin Psychopharmacol. 1998; 18 435-440
- 33 Amsterdam JD, Garcia-España F. Venlafaxine monotherapy in women with bipolar II and unipolar major depression. J Affect Disord. 2000; 59 225-229
- 34 Möller H-J, Bottlender R, Grunze H. et al . Are antidepressants less effective in the acute treatment of bipolar I compared to unipolar depression. J Affect Disord. 2001; 67 141-146
- 35 Bottlender R, Rudolf D, Jaeger M. et al . Are bipolar I depressive patients less responsive to treatment with antidepressants than unipolar depressive patients? Results from a case control study. Eur Psychiatry. 2002; 17 200-205
- 36 Ghaemi SN, Rosenquist KJ, Ko JY. et al . Antidepressant treatment in bipolar versus unipolar depression. Am J Psychiatry. 2004; 161 163-165
- 37 Agosti V, Stewart JW. Efficacy and safety of antidepressant monotherapy in the treatment of bipolar-II depression. Int Clin Psychopharmacol. 2007; 22 309-311
- 38 O’Donovan C, Julie S, Garnham JS. et al . Antidepressant monotherapy in pre-bipolar depression; predictive value and inherent risk. J Affect Disord. 2008; 107 293-298
- 39 Baldessarini RJ. Drug therapy of depression and anxiety disorders. Chapt 17 in Brunton LL, Lazo JS, Parker KL, editors Goodman and Gilman's The Pharmacological Basis of Therapeutics, eleventh edition, McGraw-Hill Press, New York; 2005: 429-459
- 40 Post RM, Altshuler LL, Leverich GS. et al . Mood switch in bipolar depressions: comparisons of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006; 189 124-131
- 41 Eppel AV. Antidepressants in the treatment of bipolar disorder: decoding contradictory evidence and opinion. Harv Rev Psychiatry. 2008; 16 205-209
- 42 Harel EV, Levkovitz Y. Effectiveness and safety of adjunctive antidepressants in the treatment of bipolar depression: a review. Isr J Psychiatry Relat Sci. 2008; 45 121-128
- 43 Nierenberg AA. Analysis of the efficacy of treatments for bipolar depression. J Clin Psychiatry. 2008; 69 (S 05) 4-8
- 44 Salvi V, Fagiolini A, Swartz HA. et al . The use of antidepressants in bipolar disorder. J Clin Psychiatry. 2008; 69 1307-1318
- 45 Vieta E. Antidepressants in bipolar depression. Acta Psychiatr Scand. 2008; 118 335-336
- 46 Baldessarini RJ, Salvatore P, Khalsa HM. et al . Morbidity in 303 first-episode bipolar I disorder patients. Bipolar Disord. 2010; 12 264-270
- 47 McElroy SL, Weisler RH, Chang W. et al . 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
- 48 Baldessarini RJ, Leahy LF, Arcona S. et al . Patterns of psychotropic drug prescription for U. S. patients with diagnoses of bipolar disorders. Psychiatr Serv. 2007; 58 85-91
- 49 Baldessarini RJ, Henk HJ, Sklar AR. et al . Use of psychotropic medicines in bipolar disorder patients in the United States. Psychiatr Serv. 2008; 59 1175-1183
- 50 Benazzi F. Does hypomania distinguish bipolar II disorder from major depressive disorder?. Psychother Psychosom. 2009; 78 55-58
Correspondence
Dr. R. J. Baldessarini
Mailman Research Center 306
McLean Hospital
115 Mill Street
Belmont
MA 02478-9106
USA
Phone: +1/617/855 3203
Fax: +1/617/855 3470
Email: rjb@mclean.org