Are antidepressants safe in the treatment of bipolar depression? A critical evaluation of their potential risk to induce switch into mania or cycle acceleration
Version of Record online: 26 AUG 2008
Copyright © 2008 The Authors. Journal Compilation © 2008 Blackwell Munksgaard
Acta Psychiatrica Scandinavica
Volume 118, Issue 5, pages 337–346, November 2008
How to Cite
Licht, R. W., Gijsman, H., Nolen, W. A. and Angst, J. (2008), Are antidepressants safe in the treatment of bipolar depression? A critical evaluation of their potential risk to induce switch into mania or cycle acceleration. Acta Psychiatrica Scandinavica, 118: 337–346. doi: 10.1111/j.1600-0447.2008.01237.x
- Issue online: 9 OCT 2008
- Version of Record online: 26 AUG 2008
- Accepted for publication June 24, 2008
- antidepressive agents;
- bipolar disorder;
- adverse effects;
Objective: To address whether switch of depression into hypomania or mania or cycle acceleration in patients with bipolar disorder is caused by antidepressants or whether this phenomenon is attributable to the natural history of bipolar disorder itself.
Method: A critical review of the literature, pointing at sources of bias that have been previously overlooked. For examining the causation in question, the Bradford–Hill criteria were applied, i.e. specificity of the potential causative agent, strength of effect, consistency in findings, dose–response relation, temporal relation with exposure to agent preceding effect and biological plausibility.
Results: There is a scarcity of randomized studies addressing the question, and the available studies all suffer from various forms of bias. However, there is some evidence suggesting that antidepressants given in addition to a mood stabilizer are not associated with an increased rate of switch when compared with the rate associated with the mood stabilizer alone.
Conclusion: When combined with a mood stabilizer, antidepressants given for acute bipolar depression seemingly do not induce a switch into hypomania or mania. Whether antidepressants may accelerate episode frequency and/or may cause other forms of destabilization in patients with bipolar disorder remain to be properly studied.