Clinical Lessons From Inappropriate Dual SNRI Prescribing

Patient Background

Linda M. is a 58-year-old female with a medical history significant for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, hypertension, osteoarthritis, and insomnia. She has no known drug allergies.

Her long-term medication regimen included venlafaxine XR 150 mg once daily, which she had been taking for approximately three years with stable control of depressive and anxiety symptoms. Additional medications included:

MEDS Current Medication List (click to expand)

Dose, route, frequency, and clinical indication.

Current Medication List

Medication	Dose	Route	Frequency	Indication
Metformin	1000 mg	Oral	Twice daily	Type 2 diabetes mellitus
Lisinopril	20 mg	Oral	Once daily	Hypertension
Hydrochlorothiazide	25 mg	Oral	Once daily	Hypertension
Gabapentin	300 mg	Oral	Three times daily	Neuropathic pain
Trazodone	50 mg	Oral	At bedtime	Insomnia / depression
Atorvastatin	40 mg	Oral	Nightly	Hyperlipidaemia
Acetaminophen	1000 mg	Oral	Three times daily (PRN)	Pain management

Clinical Presentation

Linda presented to her primary care provider with worsening burning pain in her feet, consistent with progression of diabetic peripheral neuropathy. To address neuropathic pain, duloxetine 30 mg once daily was initiated. Her existing venlafaxine XR therapy was continued unchanged.

Approximately two weeks later, Linda reported new symptoms including increased sweating, restlessness, mild tremor, nausea, and headache. Vital signs demonstrated elevated blood pressure (156/92 mmHg), which represented a notable change from her previously well-controlled readings.

Clinical Issue Identified

Medication review revealed concurrent use of two serotonin–norepinephrine reuptake inhibitors (SNRIs)—venlafaxine and duloxetine—resulting in therapeutic duplication. Both agents increase synaptic serotonin and norepinephrine, offering no additive clinical benefit when used together but substantially increasing the risk of adverse effects.

The patient’s symptoms were consistent with early serotonin toxicity and noradrenergic overstimulation, manifesting as autonomic instability, tremor, gastrointestinal upset, and blood pressure elevation. The absence of medication reconciliation at the time of duloxetine initiation contributed directly to this safety concern.

Pharmacist Intervention and Clinical Management

Identification of Therapeutic Duplication

• Recognize that concurrent venlafaxine and duloxetine therapy represents unnecessary duplicate SNRI prescribing.
• Correlate symptom onset with the addition of duloxetine.

Therapeutic Optimization

• Recommend discontinuation of one SNRI to eliminate duplication.
• If duloxetine is preferred for its dual efficacy in depression and neuropathic pain, initiate a gradual taper of venlafaxine XR rather than abrupt discontinuation.
• A reasonable strategy would include reducing venlafaxine XR to 75 mg daily upon duloxetine initiation, followed by a slow taper over several weeks to minimize withdrawal symptoms.

Monitoring and Safety

• Monitor blood pressure, heart rate, and resolution of serotonergic symptoms during medication adjustment.
• Assess for withdrawal symptoms, particularly given venlafaxine’s short half-life and high discontinuation risk.

Patient Education

• Counsel the patient on signs and symptoms of serotonin syndrome (e.g., agitation, tremor, diaphoresis, confusion, tachycardia).
• Reinforce the importance of reporting new symptoms promptly after medication changes.

Interprofessional Communication

• Communicate recommendations clearly to the prescribing provider to ensure coordinated deprescribing and documentation.

Clinical Rationale and Ramifications

This case highlights the risks associated with inadequate medication reconciliation when treating comorbid conditions. The addition of duloxetine without reassessing existing antidepressant therapy resulted in avoidable adverse effects, increased cardiovascular risk, and patient distress.

Venlafaxine, in particular, is associated with significant withdrawal symptoms if reduced too rapidly, making planned tapering essential when therapy changes are required. Failure to address therapeutic duplication could have progressed to clinically significant serotonin syndrome, emergency care utilization, or unnecessary escalation of antihypertensive therapy.

By identifying and correcting duplicate SNRI therapy, the pharmacist helps restore pharmacologic clarity, improve tolerability, and optimize treatment outcomes. This case reinforces the importance of reassessing existing therapy whenever a new medication is added, especially within the same pharmacologic class, to prevent harm and preserve patient safety.