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Antidepressant-associated switches from depression to mania in severe bipolar disorder


  • The creation of the medications chronology dataset was funded in part by a grant from Eli Lilly & Co. GAC has obtained grant funding from Eli Lilly & Co., Janssen, Abbott Laboratories and Otsuka and has served on the scientific advisory boards of those companies. SJF, LJF, QY, QW, BN, and EJB have no reported conflict of interest.

Gabrielle A Carlson, MD, Child and Adolescent Psychiatry, Stony Brook University, Putnam Hall-South Campus, Stony Brook, NY 11794-8790, USA.
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Objectives:  To determine whether switching from depression to mania is part of the natural history of bipolar illness or results from antidepressant (AD) treatment by examining bipolar patients with psychosis early in their illness course.

Methods:  A multi-facility cohort of 123 first-admission inpatients, aged 15–60 years, with DSM-IV bipolar disorder (BD) with psychotic features, was followed for four years, and 76 individuals experienced at least one episode of depression. Frequency of and risk factors for switches from depression to mania, time to switch, and duration of the subsequent manic episode were examined in relation to AD use (with anti-manic and/or antipsychotic medications).

Results:  The 76 respondents experienced 113 depressive episodes. Those prescribed ADs had more depressive episodes and spent more time depressed than non-users. A total of 23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode (20%). The time to switch and duration of the subsequent manic episode were not significantly different for the seven respondents and nine episodes involving AD treatment versus the 10 respondents and 14 episodes without ADs. None of the risk factors (age of onset ≤18 years, childhood psychopathology, depressive first episode, substance abuse at index admission, bipolar family history, type of AD used) was associated with switching.

Conclusions:  In this sample with severe BD, switching from depression to mania was not associated with AD treatment. Respondents who experienced switching appeared to have a more relentless form of BD. In only a few did ADs appear to be responsible for the switch.