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

Anders D. Westanmo; Jon Gayken; Robert Haight


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

In This Article

Formulary Considerations

Duloxetine may be a useful addition to a hospital formulary for the treatment of depression. Published guidelines emphasize the complete remission of depressive symptoms as a primary goal of antidepressant treatment. Once remission is achieved, an adequate duration of continuation and maintenance treatment may prevent symptom relapse or recurrence of a major depressive episode. Antidepressant treatments vary in providing adequate symptom control for individual patients and in their risk of adverse effects. Patient acceptance of a prescribed treatment option may greatly enhance outcomes and ensure an adequate duration of therapy. In some studies, pharmacotherapy that increases both serotonergic and noradrenergic activity has shown greater efficacy than increasing only serotonergic activity. How these data relate to duloxetine is unknown. Results of studies of depression with the other two SNRIs available worldwide, venlafaxine and milnacipran, have been mixed. Venlafaxine may increase remission rates over traditional SSRI therapy.[86] However, milnacipran has not shown any advantage over SSRIs[87,88] or tricyclic antidepressants[87,89,90] and has shown inferiority to tricyclic antidepressants in two studies.[91,92] It is uncertain if duloxetine will increase remission rates beyond what current available therapy achieves, but it may be a suitable alternative for patients who cannot tolerate or have poor outcomes with traditional antidepressant therapy. Duloxetine's combined reuptake inhibition of both serotonin and norepinephrine may decrease the risk of adverse effects related to SSRIs and may reduce the risk of affecting blood pressure compared with venlafaxine.

It is premature to recommend duloxetine for stress urinary incontinence while the major organizations do not recommend pharmacotherapy for this indication. The American Urological Association has extensive guidelines on surgical treatment but does not provide guidance on pharmacologic therapy.[93] The First International Consultation on Incontinence recommends pelvic floor muscle training exercises as a first line but stops short of recommending any sort of pharmacologic therapy.[94] A recent review states that "many physicians consider only Kegel exercises and surgery" for stress urinary incontinence.[59] It goes on to review the trials for duloxetine and concludes, "Until and unless duloxetine is approved for the treatment of stress incontinence, no strong recommendation can be made for pharmacologic therapy. Other treatment modalities are safer and possibly more effective."[59]

Duloxetine is the only drug that has been FDA approved for the treatment of pain associated with diabetic peripheral neuropathy. Despite this, there are no data showing superiority of this drug over other available treatments. Many drugs have shown benefit for pain due to diabetic peripheral neuropathy, including amitriptyline, dextromethorphan, gabapentin, oxycodone, and tramadol.[55] Among these agents, gabapentin has consistently been recommended as first line for neuropathic pain.[55,95] No peer-reviewed randomized controlled trials have been published to date evaluating duloxetine for pain due to diabetic peripheral neuropathy. Until more information is available and the methodology and outcomes of studies are subjected to peer review, duloxetine should not be recommended as a first-line treatment for neuropathic pain.