Duloxetine: A balanced and selective norepinephrine- and serotonin-reuptake inhibitor

PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, drug interactions, dosage and administration, cost, and place in therapy of duloxetine for major depression, pain from diabetic peripheral neuropathy, and stress urinary incontinence are reviewed. SUMMARY: Duloxetine is a balanced selective serotonin and norepinephrine-reuptake inhibitor available in the United States for the treatment of major depressive disorder (MDD) and diabetic peripheral neuropathic pain (DPNP). Duloxetine has also been used for the treatment of stress urinary incontinence (SUI). Absorption of duloxetine begins two hours after oral administration, reaching a maximum plasma concentration in six hours. Half-life and volume of distribution are 12 hours and 1640 L, respectively. The recommended dosage of duloxetine is 40-80 mg daily, depending on the indication, preferably split into two doses per day. For the treatment of major depression, duloxetine has achieved remission rates similar to that of existing selective serotonin-reuptake inhibitors (SSRIs). For SUI and pain associated with diabetic peripheral neuropathy, duloxetine has not demonstrated equivalence or superiority to existing therapies. The adverse effects of duloxetine are similar to those of traditional SSRIs. Nausea is common and has been cited as the primary reason for discontinuation of duloxetine in trials. Increases in blood pressure have been mild, but caution should be used in patients with hypertension. Patients with a creatinine clearance of <30 mL/min and patients with hepatic impairment should avoid duloxetine. Duloxetine should not be recommended as first-line therapy for SUI or DPNP. For MDD, duloxetine may be a useful alternative for patients who do not benefit from or are unable to tolerate other antidepressant therapy. CONCLUSION: Duloxetine has been approved for the treatment of MDD and pain associated with diabetic peripheral neuropathy in adults.