Duloxetine hydrochloride is an SNRI that is approved by the FDA for the treatment of both major depression and the pain associated with diabetic peripheral neuropathy. Interestingly, it does not appear to induce sustained treatment-emergent hypertension compared with placebo, although rare cases are possible. Its half-life is approximately 12 hours, and it is highly protein bound. The most frequent side effect is early nausea, which is dose dependent and typically transient. Like venlafaxine, duloxetine typically is not associated with significant changes in weight.