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Antidepressant Monotherapy for Bipolar Depression & Risk of Mania
In Session With Mikael Landén, MD, PhD:
Antidepressant Monotherapy for Bipolar Depression & Risk of Mania
Professor of Psychiatry, Gothenburg University; Guest Professor of Psychiatric Epidemiology,
Karolinska Institutet, Stockholm, Sweden
First published in Psychiatry Weekly, Volume 9, Issue
12, on December 15, 2014
Q: Is there a consensus across the literature regarding antidepressant-associated mania in bipolar disorder?
A: The switch-inducing property of antidepressant drugs was noted not long after their introduction in the 1950s and has been an issue since then. Although most researchers have agreed that the phenomenon is real, some have argued that it follows from a cyclical nature of bipolar disorder, in that a manic episode occurs after a depressive episode, which could be independent of any antidepressant treatment. If that were the case, one would find similar rates of manic episodes during antidepressant treatment as during other times of the illness, whereas, in our own recent study, we found an increased rate of mania after antidepressant monotherapy, which suggests that antidepressants increase the risk for mania above and beyond the baseline rate.
Q: What is known about the mechanisms potentially underlying antidepressant-associated mania in bipolar disorder?
A: There is no clear understanding of why a bipolar patient switches to another mood state, in this case from depression to mania. It has been suggested that elevated catecholamine levels related to antidepressant treatment lead to increased post-synaptic receptor sensitivity that might increase the likelihood of mania. However, there are many triggers aside from antidepressants that can incite a sudden shift to a manic state: corticosteroids, dopamine agonists, sleep deprivation, electroconvulsive treatment, and disturbed circadian rhythm. Each of these triggers operates via discrete mechanisms of action.
Q: What type of data did your study include, and what were the main findings?
A: The methodological strength of this paper is that we made comparisons within individuals rather than between groups of people. We call this a “within-individual design.” We did not simply compare bipolar patients with and without antidepressant prescription but compared periods with and without antidepressant treatment for the same individual. We used national Swedish registers, which allow for long-term follow-up and provide robust statistical power.
Based on our findings, we could confirm that treatment-emergent mania is more likely to occur in bipolar patients receiving antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). We did not observe treatment-emergent mania in bipolar patients who received a concomitant mood stabilizer (HR=0.79, 95% CI=0.54, 1.15). In fact, we found a decreased risk for mania in the longer term (4–9 months) in patients receiving both mood-stabilizer and antidepressant treatments. Therefore, if an antidepressant agent is indicated to treat bipolar depression, patients need to receive a mood stabilizer first.
It should be noted that only a small fraction of patients in this study actually developed mania. On the other hand, we relied on a hospital discharge register, which might not have captured elated hypomanic episodes. Finally, this study does not address the longstanding question regarding the effectiveness of antidepressants in treating bipolar depression.
Disclosure: Dr. Landén has received speaking fees from Biophausia, Sweden.
References:
1. Viktorin A, Lichtenstein P, Thase ME, et al. The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer. Am J Psychiatry. 2014;171:1067-1073.