Duplicate Antidepressant Therapy – Sertraline and Duloxetine

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In this case scenario, I review a common situation I’ve encountered with duplicate antidepressant therapy. JS is a 67-year-old male with a history of type 2 diabetes, peripheral neuropathy, and depression. He has been taking sertraline (podcast) 100 mg daily for over a year, but both he and his provider have noticed little improvement in mood. During a recent visit, JS also reports worsening foot pain related to diabetic neuropathy, which has been limiting his sleep and activity levels.

In response, the provider starts duloxetine (podcast) 30 mg daily, hoping it will help with both depression and neuropathic pain. However, the sertraline is not discontinued, and the patient ends up taking both medications together. Using drugs with an overlapping mechanism of action is a pet peeve of mine. It appears that sertraline hasn’t been very effective and that there is no solid reason to continue it.

Both medications increase serotonin, and when used together, can raise the risk of serotonin syndrome, as well as unnecessary polypharmacy. Given that sertraline was ineffective after an adequate trial, continuing it offers no clinical benefit and adds potential harm.

The pharmacist recommends discontinuing sertraline while gradually titrating up duloxetine to an appropriate target dose for combined mood and pain benefit. Simplifying the regimen not only reduces side effect risk but also improves adherence and therapeutic focus on one antidepressant with dual benefit.

When switching from an SSRI like sertraline to an SNRI such as duloxetine, it’s important to taper and discontinue the first agent rather than overlap them long term. Unnecessary duplicate antidepressant therapy increases serotonin-related adverse effects and confusion over which medication is actually working. Always reassess for efficacy before adding another antidepressant—sometimes, simplifying the regimen is the safest and most effective step.

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