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

Dosage and Administration

The recommended dosage of duloxetine for MDD is 40 to 60 mg per day, given either once a day or in divided doses twice daily.[25] Studies have shown that four to eight weeks of therapy at the recommended dosage is optimal at achieving a response,[78,79] and guidelines reflect this time frame.[37,38] If a patient does respond to drug therapy, treatment should be maintained for another 6 months for a total of 9 to 12 months of treatment.[37] In clinical practice, patients often do not receive the appropriate length of treatment because of inadequate dosing or duration, limited access, or non-compliance.[80,81] If a patient does not respond to a particular medication within four to six weeks, treatment with this medication should continue for an additional two to four weeks at the maximum tolerated dosage. If no response is noted at that time, the medication should be changed. Patients who are at high risk of relapse should be maintained at the effective dosage beyond six months, and possibly indefinitely.[82]

For diabetic peripheral neuropathic pain, the recommended dosage is 60 mg per day, although dosages of up to 120 mg daily have been studied.[25] Higher dosages do not have proven benefit and may increase the risk of adverse effects.

The approved dosage of duloxetine for treatment of stress urinary incontinence in Europe is 80 mg per day (40 mg twice per day).[83] This recommendation is based on experience in approximately 1000 women ages 18 to 84 years who were randomized to receive this dosage of duloxetine in four stress incontinence trials.[65–68] If patients continue to experience adverse effects beyond the initial four weeks of treatment, the European prescribing information states that the dosage may be reduced to 20 mg twice daily.[69]

In duloxetine studies for any indication, there seem to be dosage-related adverse effects. The authors of one study of duloxetine for stress incontinence stated that it would be reasonable to initiate duloxetine at 10 or 20 mg twice per day for the first two to three days of therapy.[84] This recommendation was based on the percentage of patients (25%) who dropped out of the study because of adverse effects. The number of patients treated with duloxetine for stress urinary incontinence has far exceeded the number treated for depression or pain; thus, the authors' recommendations seem reasonable.

No dosage adjustment is necessary in patients with mild renal impairment (CLcr, ≥ 30 mL/min).[25] Patients with a CLcr of < 30 mL/min should not take duloxetine.[25] Patients with any degree of hepaticimpairment should also be advised not to take duloxetine. The manufacturer of duloxetine recommends tapering the dosage of duloxetine if it is being discontinued.[25]

Duloxetine is rapidly degraded in an acidic environment, so the enteric-coated tablets should not be crushed or split.[25] The product is available in 20-, 30-, and 60-mg capsules with average wholesale prices of $3.18, $3.56, and $3.56, respectively ( Table 3 ).[85]