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According to DSM-IV diagnostic criteria, bipolar disorder (bipolar affective disorder, manic-depressive disorder) is characterized by marked mood swings between mania (mood elevation) and depression. The essential feature of bipolar I disorder (BDI) is a clinical course that is defined by the occurrence of 1 or more manic or mixed episodes; the essential feature of bipolar II disorder (BDII) is a clinical course that is defined by the occurrence of 1 or more major depressive episodes accompanied by at least 1 hypomanic episode. As such, bipolar disorder can cause significant personal distress and social dysfunction.
Bipolar disorder has been subdivided in several ways, but classically there are 2 clinical categories of the disorder. BDI is characterized by the occurrence of 1 or more manic or mixed episodes (mixed episode means that symptoms of mania and depression are present at the same time). Often individuals with BDI have also had 1 or more major depressive episodes. Episodes of substance-induced mood disorder (caused by the direct effects of a medication, other somatic treatments for depression, drug abuse, or toxin exposure) or of mood disorder caused by a general medical condition are not considered when making a diagnosis of bipolar disorder. By contrast, BDII is diagnosed when depression is interspersed with less severe episodes of elevated mood that do not lead to dysfunction or disability (hypomania).
Although individuals with BDI can return to a fully functional level between episodes, some continue to display mood lability and interpersonal or occupational difficulties. Manic symptoms are the hallmark of the illness and can represent a real medical emergency. However, bipolar depression is often much more clinically significant.1
Depression was the third leading cause of burden among all diseases in 2002, and it is expected to rise in the next 20 years.2 Evidence suggests that depressive episodes and symptoms are equal to or more disabling than corresponding levels of manic or hypomanic symptoms and that only subsyndromal depressive symptoms (and not subsyndromal manic or hypomanic symptoms) are associated with significant impairment in patients with bipolar disorder.3 This scenario highlights the need for effectively treating bipolar depression.
Although antidepressant drugs remain the mainstay of treatment for unipolar major depression in both primary and secondary care settings,4 the evidence to support antidepressant treatment for bipolar depression is limited and increasingly controversial—especially now that evidence is available for alternative medications, including quetiapine and lamotrigine.5
Apart from the limited evidence, a key problem with antidepressants is the potential for increasing the risk of iatrogenic episodes of elevated mood. This is the reason many reviews and guidelines for bipolar depression have recommended the use of a mood stabilizer (usually lithium or valproate) rather than an antidepressant as the first-line treatment for bipolar depression.6,7 Antidepressants are advised only as second-line treatment and always with a concurrent mood stabilizer to prevent switching to mania. However, in real-world clinical practice, antidepressants are still frequently prescribed for bipolar disorder.8 Thus, 3 important clinical questions arise: (1) What is the effectiveness (if any) of antidepressants in bipolar depression? (2) What is the risk of manic switching? (3) How effective are antidepressants in preventing relapse of bipolar depression?
1. Ostacher MJ. The evidence for antidepressant use in bipolar depression. J Clin Psychiatry. 2006; 67:18-21.
2. World Health Organization. WHO Collaborating Centre for Drug Statistics Methodology. Available at: http:// www.whocc.no/atcddd/. Accessed May 31, 2007.
3. Judd LL, Akiskal HS, Schettler PJ, et al. Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study. Arch Gen Psychiatry. 2005;62:1322-1330.
4. National Institute for Clinical Excellence. Depression: Management of Depression in Primary and Secondary Care. London: National Institute for Clinical Excellence; 2004.
5. National Institute for Health and Clinical Excellence (NICE). Bipolar disorder: the management of bipolar disorder in adults, children and adolescents, in primary and secondary care. London: NICE; 2006. Available at: http://guidance.nice.org.uk/page.aspx?o= 384826. Accessed May 29, 2007.
6. Thase ME. Pharmacotherapy of bipolar depression: an update. Curr Psychiatry Rep. 2006;8:478-488.
7. Goodnick PJ. Bipolar depression: a review of randomised clinical trials. Expert Opin Pharmacother. 2007;8:13-21.
8. Blanco C, Laje G, Olfson M, et al. Trends in the treatment of bipolar disorder by outpatient psychiatrists. Am J Psychiatry. 2002;159:1005-1010.
9. Gijsman HJ, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004; 161:1537-1547.
10. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356:1711-1722.
11. Post RM, Leverich GS, Nolen WA, et al, for the Stanley Foundation Bipolar Network. 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.
12. Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006;163:232-239.
13. Post RM, Altshuler LL, Leverich GS, et al. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006;189:124-131.
14. Smith D, Dempster C, Glanville J, et al. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry. 2002;180: 396-404.
15. Hansen RA, Gartlehner G, Lohr KN, et al. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med. 2005;143:415-426.
16. Solomon DA, Keitner GI, Miller IW, et al. Course of illness and maintenance treatments for patients with bipolar disorder. J Clin Psychiatry. 1995;56:5-13.
17. Sachs GS, Thase ME, Otto MW, et al. Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2003;53:1028-1042.
18. Perlis RH, Ostacher MJ, Patel JK, et al. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry. 2006; 163:217-224.
19. Ghaemi SN, Lenox MS, Baldessarini RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry. 2001;62: 565-569.
20. Geddes J. Bipolar disorder. Clin Evid. 2005;13: 1158-1181.
21. McElroy SL, Kotwal R, Kaneria R, Keck PE Jr. Antidepressants and suicidal behavior in bipolar disorder. Bipolar Disord. 2006;8:596-617.
22. Bauer MS, Wisniewski SR, Marangell LB, et al. Are antidepressants associated with new-onset suicidality in bipolar disorder? A prospective study of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). J Clin Psychiatry. 2006;67:48-55.
23. Cipriani A, Barbui C, Geddes JR. Suicide, depression, and antidepressants. BMJ. 2005;330:373-374.