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