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Sex Differences in the Effect of Atomoxetine on the QT Interval in Adult Patients With Attention-Deficit Hyperactivity Disorder

Suzuki, Yutaro MD, PhD; Tajiri, Misuzu MD; Sugimoto, Atsunori MD, PhD; Orime, Naoki MD; Hayashi, Taketsugu MD; Egawa, Jun MD, PhD; Sugai, Takuro MD, PhD; Inoue, Yoshimasa; Someya, Toshiyuki MD, PhD

Journal of Clinical Psychopharmacology: February 2017 - Volume 37 - Issue 1 - p 27–31
doi: 10.1097/JCP.0000000000000630
Original Contributions
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Background The effects of atomoxetine on QT in adults remain unclear. In this study, we examined whether the use of atomoxetine to treat attention-deficit hyperactivity disorder in adults is associated with QT prolongation.

Methods Forty-one subjects with attention-deficit hyperactivity disorder were enrolled in this study. Participants were administered 40, 80, or 120 mg atomoxetine daily and were maintained on their respective dose for at least 2 weeks. We conducted electrocardiographic measurements and blood tests, measuring plasma atomoxetine concentrations after treatment. Electrocardiograms of 24 of the patients were also obtained before atomoxetine treatment. The QT interval was corrected using Bazett (QTcB) and Fridericia (QTcF) correction formulas.

Results In these 24 patients, only the female patients had prolonged QTcB (P = 0.039) after atomoxetine treatment. There was no correlation between plasma atomoxetine concentrations and the corrected QT interval (QTc), or between atomoxetine dosage and the QTc. However, in female patients, there was a significant positive correlation between atomoxetine dosage and the QTcB (r = 0.631, P = 0.012), and there was a marginally significant positive correlation between atomoxetine dosage and the QTcF (r = 0.504, P = 0.055). In male patients, there was no correlation between atomoxetine dosage and the QTcB or QTcF intervals. There was no correlation between plasma atomoxetine concentrations and the QTc in either female or male patients.

Implications Clinicians should exhibit caution when prescribing atomoxetine, particularly for female patients.

From the *Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences; †Department of Psychiatry; ‡Niigata Psychiatric Center, Niigata University Medical and Dental Hospital, Niigata; and §Techno-Pharma, Fukuoka, Japan.

Received April 5, 2016; accepted after revision September 28, 2016.

Reprints: Yutaro Suzuki, MD, PhD, Department of Psychiatry, Niigata University Medical and Dental Hospital, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan (e-mail: yutaro@med.niigata-u.ac.jp).

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