Sertraline and Duloxetine Co-Administration: A Case of Duplicate Antidepressant Therapy

Patient Background:

John, a 67-year-old male, has a medical history significant for type 2 diabetes mellitus, peripheral neuropathy, and major depressive disorder. He has been maintained on sertraline 100 mg daily for over one year. Despite adherence to therapy, both the patient and his healthcare provider report minimal improvement in depressive symptoms.

Clinical Presentation:

During a recent consultation, John reported worsening neuropathic foot pain, which had begun to interfere with his sleep quality and daily functioning. In an attempt to address both depressive symptoms and neuropathic pain, the prescriber initiated duloxetine 30 mg daily. However, sertraline was inadvertently continued, resulting in concurrent therapy with two serotonergic antidepressants.

Clinical Issue Identified:

The simultaneous use of sertraline (SSRI) and duloxetine (SNRI) represents therapeutic duplication, as both agents act through serotonin reuptake inhibition. This overlap provides no additional antidepressant benefit and increases the risk of serotonin syndrome, additive adverse effects (e.g., nausea, agitation, diaphoresis, tremor), and polypharmacy-related complications such as reduced adherence and confusion regarding therapeutic response.

Pharmacist Intervention and Management:

Upon medication review, the pharmacist identified the duplication and advised the following management plan:

Gradual Discontinuation of Sertraline:

• Taper sertraline over 1–2 weeks to prevent withdrawal symptoms (e.g., dizziness, insomnia, irritability).
• Monitor for discontinuation symptoms and emerging mood changes.

Optimization of Duloxetine Therapy:

• Continue duloxetine 30 mg daily for 1–2 weeks, then titrate to 60 mg daily, the typical therapeutic dose for both depression and diabetic neuropathic pain.
• Monitor for blood pressure changes, gastrointestinal upset, and potential serotonin-related adverse effects during transition.

Patient Education:

• Explain the rationale for discontinuing sertraline to avoid overlap.
• Reinforce the importance of adherence to the single antidepressant regimen.
• Advise the patient to report symptoms of serotonin toxicity (e.g., agitation, confusion, sweating, tremor, or muscle rigidity) promptly.

Follow-Up:

• Schedule follow-up in 4–6 weeks to assess mood improvement, neuropathic pain relief, and tolerability of duloxetine.
• Coordinate care with the prescriber to ensure medication reconciliation and update the treatment plan.

Clinical Rationale and Ramifications

Failure to recognize therapeutic duplication between antidepressants can lead to serious clinical consequences, including serotonin syndrome, increased adverse effects, and unnecessary medication burden. In John’s case, the absence of benefit from sertraline after an adequate trial suggests that continuing it offers no therapeutic justification.

The pharmacist’s intervention prevented potential serotonin toxicity and streamlined therapy to a single, rationally selected agent—duloxetine, which offers dual efficacy in mood and neuropathic pain management. Simplifying the regimen improves safety, enhances adherence, and supports clearer evaluation of treatment response.