Is treatment-associated hypomania rare with duloxetine: secondary analysis of controlled trials in non-bipolar depression.
BACKGROUND
Selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors (SNRIs) like duloxetine have the efficacy of tricyclic antidepressants (TCAs) with a more tolerable side-effect profile. Bipolar disorder is often undetected, with the most common misdiagnosis being unipolar depression. Studies have suggested that treatment of bipolar and unipolar depression with heterocyclic TCAs may increase the risk of switch rate to mania. Studies of antidepressants in unipolar major depression show a small risk of mania or hypomania, presumably because some bipolar depressives were mistakenly studied. This study investigated the rate of hypomania, mania, and hypomanic-like symptoms observed during treatment with duloxetine in patients with major depression.


METHODS
This was a retrospective analysis of data from eight placebo-controlled, double-blind, randomized clinical trials of duloxetine in patients with non-bipolar major depression.


CONCLUSIONS
The studies were of limited duration. Manic or hypomanic symptoms were not elicited using standardized mania rating scale instruments.


RESULTS
One case of mania occurred in the placebo group (0.1%), and two cases of hypomania were observed in the duloxetine-treated group (0.2%). Among hypomanic-like symptoms, only insomnia was significantly higher in the duloxetine group than in the placebo group (p<0.05).


CONCLUSIONS
Duloxetine was associated with a low incidence of treatment-emergent hypomania, mania, or hypomanic-like symptoms in patients with major depressive disorder (MDD). The low incidence reported here may be due to greater diagnostic diligence on the part of the investigators. It is possible that the cases reported likely reflect inclusion of misdiagnosed bipolar II patients rather than true unipolar MDD cases. The effect of duloxetine in patients with bipolar depression is not known.
Dunner
David L
DL
Department of Psychiatry and Behavioral Sciences, University of Washington Center for Anxiety and Depression, 4225 Roosevelt Way NE, Ste 306C, Seattle, WA 98105, United States. ddunner@u.washington.edu
D'Souza
Deborah N
DN
Kajdasz
Daniel K
DK
Detke
Michael J
MJ
Russell
James M
JM
D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
D000068736:Duloxetine Hydrochloride; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes