Profile of Adverse Events with Duloxetine Treatment A Pooled Analysis of Placebo-Controlled Studies

Background: The serotonin and noradrenaline (norepinephrine) reuptake inhibitor duloxetine has been approved in the US and elsewhere for a number of indications, including psychiatric illnesses and chronic pain conditions. Because the patient populations are diverse within these approved indications, and duloxetine is not yet approved for treatment of other conditions, we wanted to determine if adverse event profiles would differ among patients being treated for these various conditions. Objective: To provide detailed information on the adverse events associated with duloxetine and to identify differences in the adverse event profile between treatment indications and patient demographic subgroups. Methods: Data were analysed from all placebo-controlled trials of duloxetine completed as of December 2008. The 52 studies included 17 822 patients (duloxetine n = 10326; placebo n = 7496) with major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, osteoarthritis knee pain (OAKP), chronic lower back pain and lower urinary tract disorders. The main outcome measures were rates of treatment-emergent adverse events (TEAEs) and adverse events reported as the reason for discontinuation. Results: The overall TEAE rate was 57.2% for placebo-treated patients and 72.4% for duloxetine-treated patients (p <= 0.001). Patients with OAKP had the lowest TEAE rate (placebo 36.7% vs duloxetine 50.2%, p <= 0.01), while patients with fibromyalgia had the highest rate (placebo 80.0% vs duloxetine 89.0%, p <= 0.001). The most common TEAE for all indications was nausea (placebo 7.2% vs duloxetine 23.4%, p <= 0.001), which was predominantly mild to moderate in severity. No statistically significant treatment-by-subgroup interactions for age were found between placebo and duloxetine treatment for the most common TEAEs. The rates of duloxetine-associated dry mouth and fatigue were greater in women than in men (13.1% vs 10.4%, interaction p = 0.004; and 9.4% vs 7.6%, interaction p = 0.03, respectively). Duloxetine-associated dry mouth incidence was higher in Caucasians than non-Caucasians (13.2%, 11.0%, interaction p = 0.04). Conclusions: Duloxetine treatment is associated with significantly higher rates of common TEAEs versus placebo, regardless of indication or demographic subgroup. Differences across indications are likely to be attributable to the underlying condition rather than duloxetine, as suggested by the similar trends observed in placebo- and duloxetine-treated patients.