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Although, a mood stabilizer monotherapy can be an effective bipolar disorder treatment in some patients, for others, improvement will be insufficient. For patients who have an inadequate antidepressant response to mood stabilizer monotherapy, antidepressants are often added. This common clinical situation raises at least 3 important considerations:
- During a bipolar disorder treatment, are there differential risks of switching among the available antidepressants when added to mood stabilizers?
- How protective are mood stabilizers against the risk of switching?
- After a patient experiences a marked response to a mood stabilizer-antidepressant combination, what are the risks of continuing this combination on switching, compared with the risk of discontinuing the antidepressant and depressive relapse?
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Calabrese and colleagues [Note 2] recently reviewed the reported switch rates from randomized controlled trials in acute bipolar disorder treatment. Overall, these studies suggest that the lowest switch rates were associated with lithium, lamotrigine, olanzapine, OFC, and paroxetine (administered with a mood stabilizer).
Three recent studies examined the efficacy of mood stabilizers in preventing switching with the addition of an antidepressant during the bipolar disorder treatment.[Notes 3-5] Bottlender and colleagues [Note 2] reported an overall switch rate of 25% in a cohort of 158 inpatients subject to a bipolar disorder treatment. Risk factors for switching were administration of a tricyclic antidepressant, particularly without a mood stabilizer. Patients who switched were significantly less likely to be receiving a concomitant mood stabilizer. These findings on bipolar disorder treatment were consistent with earlier reports that described a reduction in switch risk by approximately 50% if an antidepressant was added to a mood stabilizer compared with no mood stabilizer.[Notes 6,7] Henry and colleagues [Note 4] also found a relatively low switch rate of 27% in a cohort of 44 patients receiving antidepressants in naturalistic trials. Patients receiving a mood stabilizer, particularly lithium, were at one third the risk of switching over the 6 week bipolar disorder treatment interval. Post and colleagues [Note 5] examined switch rates in an interim analysis of an ongoing trial comparing the addition of bupropion, sertraline, and venlafaxine to mood stabilizers over an acute 10-week period, followed by 1 year of maintenance treatment in responders. The switch rate was 14% in the acute treatment trials (mania 6%, hypomania 7%) and 33% during the one year follow-up (mania 13%, hypomania 21%). No antidepressant was associated with a significantly higher switch rate.
These studies on bipolar disorder treatment indicate that concomitant administration of an antidepressant with a mood stabilizer does not eliminate but does significantly reduce the risk of switching. The studies of Henry and colleagues and Post and colleagues found that hypomanic rather than manic switches were quite common.
The bipolar disorder treatment over the long-term raises the final question of how long to maintain an antidepressant once a patient has experienced a remission of symptoms, balancing the risk of depressive relapse with the risk of switching. Two studies by Altshuler and colleagues [Notes 8,9] recently examined this question. The first study compared relapse rates of 25 patients who discontinued antidepressants (administered with mood stabilizers) with 19 patients who continued on antidepressants (with mood stabilizers).[Note 8]
The group that discontinued antidepressants in the bipolar disorder treatment had a threefold higher risk of depressive relapse compared with the group that continued on antidepressants. In contrast, the group that continued antidepressants did not have a significantly higher switch risk. The second study on bipolar disorder treatment examined the same issue in a cohort of 84 patients from the Stanley Foundation Bipolar Treatment Network.[Notes 5,9] At 1-year follow-up, patients who discontinued antidepressants within 6 months of achieving remission from depression were twice as likely to experience a depressive relapse with antidepressant discontinuation compared with patients who continued these agents (bupropion, sertraline, venlafaxine). There was no significant difference in depressive relapse rates between the 2 groups. These 2 studies on bipolar disorder treatment suggest that the risk of depressive relapse with antidepressant discontinuation was high relative to the risk of switching with antidepressant continuation. Two cautionary notes to consider, however, are that these findings on bipolar disorder treatment do not necessarily generalize to rapid cycling patients, and the comparatively low switch rates may have been attributable to the use of antidepressants with low switch rates themselves. [Note 1]
For additional information on the subject of Bipolar Disorder Treatment, click here.
Notes to this article on Bipolar Disorder Treatment
1. Keck PE Jr, McElroy SL. New approaches in managing bipolar depression. J Clin Psychiatry. 2003;64(suppl 1):13-18. Abstract
2. Calabrese JR, Rapport DJ, Kimmel SE, et al. Controlled trials in bipolar I depression: focus on switch rates and efficacy. Eur Neuropsychopharmacol 1999(suppl 4):109-112.
3. Bottlender R, Rudolf D, Strauss A, et al. Mood-stabilizers reduce the risk for developing antidepressant-induced maniform states in acute treatment of bipolar I depressed patients. J Affect Disord. 2001;63:79-83. Abstract
4. Henry C, Sorbara F, Lacoste J, et al. Antidepressant-induced mania in bipolar patients: identification of risk factors. J Clin Psychiatry. 2001;62:249-255. Abstract
5. Post RM, Altshuler LL, Frye MA, et al. Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers. Bipolar Disord. 2001;3:259-265. Abstract
6. Boerlin J, Gitlin MJ, Zoellner LA, et al. Bipolar depression and antidepressant-induced mania: a naturalistic study. J Clin Psychiatry. 1998;59:374-379. Abstract
7. Rouillon F, Lejoyeaux M, Filteau MJ. Unwanted effects of long-term treatment. In: Montgomery SA, Rouillon FA, eds. Long-term Treatment of Depression. New York, NY: Wiley; 1992:81-111.
8. Altshuler LL, Kiriakos L, Calcagno J, et al. The impact of antidepressant discontinuation versus antidepressant continuation on 1-year risk for relapse of bipolar depression: a retrospective chart review. J Clin Psychiatry. 2001;62:612-616. Abstract
9. Altshuler LL, Suppes T, Black D, et al. The impact of antidepressant discontinuation after acute remission from bipolar depression on rates of depressive relapse at one-year follow-up. Am J Psychiatry. 2003; In press.
Source : Medscape
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