Duloxetine: A Balanced and Selective Norepinephrine and Serotonin-Reuptake Inhibitor

Anders D. Westanmo; Jon Gayken; Robert Haight

Disclosures

Am J Health Syst Pharm. 2005;62(23):2481-2490. 

In This Article

Safety

The adverse-effect profile of duloxetine is similar to that of SSRIs. Common adverse effects of duloxetine at various dosages for depression are described in Table 2 . The majority of these adverse effects were mild to moderate. Nausea has been the most frequently reported adverse effect of duloxetine and the most common cause of adverse-event-related discontinuation.[44–47,69] In one trial using duloxetine 60 mg once daily, 80% of patients experienced nausea within the first week of treatment.[44] In another clinical trial, 22% of patients withdrew because of adverse events, with nausea being the most commonly cited reason.[66] Although poorly understood, SSRI-induced nausea has been inhibited by ondansetron.[27]

There is a slight risk of mild hypertension with duloxetine. In patients taking venlafaxine, increases in diastolic blood pressure of 1 mm Hg occur in approximately 5%.[70] Since this effect is speculated to be due to noradrenergic potentiation, duloxetine also may be expected to have similar effects.[71] In studies of duloxetine for MDD, average increases of 2 mm Hg in systolic and 0.5 mm Hg in diastolic blood pressure have been observed.[25] The manufacturer advises practitioners to measure blood pressure prior to treatment and periodically thereafter.[25] Heart rate has also been elevated by an average of 2–3 beats/min in patients taking duloxetine.[25] This increase was significant compared with placebo but not considered clinically significant. Because of the possibility of effects on blood pressure and heart rate, antidepressants with actions on norepinephrine should be used with caution in patients with hypertension, tachycardia, or other cardiovascular or cerebrovascular disorders.[29]

During placebo-controlled trials of duloxetine in patients diagnosed with MDD, the following sexual adverse effects were reported in the groups receiving duloxetine (n = 1139): decreased libido (3%), abnormal orgasm (3%), erectile dysfunction (4%), delayed ejaculation (3%), and ejaculatory dysfunction (3%). In all categories, the corresponding rate of these effects in patients randomized to placebo (n = 777) was 1%.[25] The Arizona Sexual Experience Scale (ASEX) is a validated measure of sexual dysfunction.[72] As rated by the ASEX, patients receiving duloxetine experienced a significant increase in sexual dysfunction (p <0.001) in the category of ease of reaching orgasm.[25] Clinicians are advised to routinely inquire about possible sexual adverse effects in patients receiving duloxetine.[25]

Patients with MDD may experience worsening of their depressive symptoms or the emergence of suicidal ideation and behavior, whether or not they are taking antidepressant medications. This risk may continue until significant remission occurs. Although there has been concern regarding the role of antidepressant medications in worsening depressive symptoms and the emergence of suicidality in certain patients, a causal role for antidepressants has not been established. Patients receiving antidepressant medications should be closely observed for worsening symptoms and suicidality, especially during and following initiation of treatment or during dosage adjustments.[25] During premarketing clinical trials of duloxetine, suicide attempt and completed suicide were infrequent adverse events (occurring in 1/100 to 1/1000 of patients). During a large long-term (one-year) safety and efficacy trial, 7 suicide attempts corresponded to one attempt per 115 patient-years of duloxetine exposure.[73] If patients, family members, or caregivers experience or observe increased depressive symptoms, agitation, irritability, or the emergence of suicidal thoughts during treatment with duloxetine or any antidepressant medication, they should report these symptoms immediately to a health care provider.[25]

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