Brief reportAntidepressant-associated mood-switching and transition from unipolar major depression to bipolar disorder: A review
Introduction
Many cases of bipolar disorder (BPD) present in episodes of major depressive disorder (MDD), accounting for approximately half of initial episodes (Goodwin and Jamison, 2007, Tondo et al., 2010b, Etain et al., 2012). Many such patients risk switching of mood from depression to disruptive and potentially dangerous manic/hypomanic, mixed, or psychotic states, sometimes in association with treatment with a mood-elevating agent, and some require re-diagnosis to BPD (Lim et al., 2005, Visser and Van der Mast, 2005, Tondo et al., 2010a, Li et al., 2012). Such risk may be particularly high among juvenile depressed patients, who are more likely to be treated with antidepressants (ADs) and stimulants before a diagnosis of BPD is made (Martin et al., 2004, Baldessarini et al., 2005, Lim et al., 2005, Biederman et al., 2009, Offidani et al.,). Moreover, patients who begin BPD with depressive or mixed episodes appear to be at increased risk for long-term morbidity, disability, and suicide (Baldessarini et al., 2010a, Baldessarini et al., 2010b, Baldessarini et al., 2012b). These considerations indicate the importance of quantifying the risk of excessive elevation of mood and behavioral activation during treatment with mood-elevating drugs, and its relationship to later diagnoses of BPD supported by spontaneous mood-elevations (Strober and Carlson, 1982, Akiskal et al., 1983). Finally, it remains unclear to what extent AD-associated mood-switches represent uncovering of potential or unrecognized BPD, or a more direct pharmacologic effect independent of diagnosis (Tondo et al., 2010a, Offidani et al.,).
Accordingly, we carried out a systematic review of reports on AD-associated mood-switching among patients diagnosed with MDD, as well as of reports on diagnostic conversion from MDD to BPD. We aimed to clarify the rates of each phenomenon and to seek relationships between them, as well as considering the possible significance of AD-associated mood-switching.
Section snippets
Methods
We supplemented two recent systematic literature searches (Tondo et al., 2010a, Offidani et al.,) for reports pertaining to manic-switching during AD-treatment and to diagnostic change to BPD in MDD patients identified in several computerized databases to September, 2012: Best Evidence (from 1991); Centre for Reviews and Dissemination; CINAHL database; Cochrane Library; EMBASE (from 1980); ISI database; MEDLINE-PubMed (from 1966); PsychInfo; PsycLIT (from 1967); Thomson–Reuters; and
Results
Rate of mood-switching with antidepressants
Reports of AD-treatment-associated mood-switching (n=51; Table 1) included a total of 95,786 depressed patients of a range of ages, treated and followed for times varying from 4 weeks to 23 years (mean: 2.39±2.99 years; median: 1.00 [IQR: 0.20–3.75]). The overall rate of mood-switching into mania, hypomania, or mixed-states was 8.18% (7837/95,786), compared to the mean±SD of rates from individual studies of 10.9±11.4% (95% CI: 7.73–14.1). Owing to the
Discussion
We found new mania-like reactions (“mood-switches”) during AD-treatment among patients diagnosed with unipolar MDD, at an average frequency of 8.18% of cases, or approximately 3.42 %/year of treatment (Table 1). Rates of new diagnoses of BPD among patients diagnosed with MDD averaged 3.29%, or 0.61 %/year (Table 2). These findings indicate 2.5–5.6-fold excess of mood-switches to re-diagnoses, although reported rates of both AD-associated mood-switches and of changed diagnoses to BPD are both
Role of funding source
None
Conflict of interest
No author or close family member has financial or other relationships with commercial or industrial entities that might represent potential conflicts of interest in the material presented. Funding sources had no role in the analysis, interpretation, or presentation of the content of this report.
Acknowledgments
Supported, in part, by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Research fund (to RJB).
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