To The Editor: Duloxetine is a dual antidepressant. According to Viktrup et al. (1), duloxetine does not induce mania or hypomania in women without a history of major depression. Moreover, pooled data by Dunner et al. (2) show that the estimated risk of duloxetine-related manic switching is 0.1% to 0.2% in patients with major depression. However, the methodological limitations of the study conducted by Dunner et al. as well as the scarcity of other sources of information lead us to believe that the actual risk of manic switching with duloxetine remains unknown. We present two clinical cases in which manic switching occurred after treatment with duloxetine.
A 58-year-old man with a 2-month major depressive episode was seen in our outpatient clinic. There were no psychiatric antecedents, and both the patient and his family denied any episodes suggesting mania or hypomania. The patient did not have a family history of bipolar disorder, and his medical history was unremarkable.
Treatment with paroxetine (40 mg daily) resulted in initial partial remission, followed by severe relapse. Duloxetine (60 mg daily) was substituted and rapid recovery was obtained. Four months later—while still on duloxetine—admission was necessary because the patient experienced a manic syndrome with psychotic features. General examination and routine studies (rapid plasma reagin, human immunodeficiency virus, thyroid function, blood chemistry, and computed tomography scan) showed results within normal limits.
The second patient was a 40-year-old woman who had previously showed symptoms of bulimia and alcohol abuse. She also had interspersed periods of increased activity with times of more inhibition, for which medical care was never required. Several months before, she suffered a transient, acute psychotic episode that required hospital admission and short treatment with an atypical antipsychotic. Her status at the time included anhedonia, hypersomnia, anergy, difficulty in concentrating, and a sense of worthlessness. Six weeks after beginning treatment with duloxetine, the patient’s mood improved. Nevertheless, after 3 months of treatment (120 mg daily), a sudden manic episode with psychotic symptoms was diagnosed, and inpatient management was required.
An increased risk of manic switching with venlafaxine (3), which is also a dual agent, has been reported. Although anecdotal, our two case studies warn against the risk of duloxetine. In both our patients, episodes were extremely severe. One patient had been treated with a selective serotonin reuptake inhibitor, but only after treatment with duloxetine did manic switching occur.
In our opinion, clinicians should carefully observe early warning signs of mania in patients with seemingly unipolar depressive disorders who are undergoing treatment with dual antidepressants.
1.Viktrup L, Perahia DG, Tylee A: Duloxetine treatment of stress urinary incontinence in women does not induce mania or hypomania. Prim Care Companion J Clin Psychiatry 2004; 6:239–2432.Dunner DL, D"Souza DN, Kajdasz DK, Detke MJ, Russell JM: Is treatment-associated hypomania rare with duloxetine?: secondary analysis of controlled trials in non-bipolar depression. J Affect Disord 2005; 87:115–1193.Post RM, Altshuler LL, Leverich GS, Frye MA, Nolen WA, Kupka RW, Suppes T, McElroy S, Keck PE, Denicoff KD, Grunze H, Walden J, Kitchen CM, Mintz J: Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry 2006; 189:124–131
Dr. de Dios has received honoraria for CME activity from Eli Lilly, Pfizer, Bristol-Myers Squibb, and Wyeth; she has lectured and received grants from AstraZeneca, Eli Lilly, Pfizer, Janssen, Bristol-Myers Squibb, and Wyeth; she has also received travel funds from Eli Lilly and Bristol-Myers Squibb. Dr. Ezquiaga has received honoraria for CME activity from Eli Lilly and Lundbeck; she has lectured and received grants from Eli Lilly and Lundbeck; she has also received travel funds from Eli Lilly.