What is an overdose of desvenlafaxine (Pristiq)?

Desvenlafaxine Overdose

Desvenlafaxine overdose typically causes mild toxicity with tachycardia, hypertension, and nausea, but serious complications including seizures, serotonin syndrome, QT prolongation, and death can occur, particularly with co-ingestions. 1

Clinical Presentation

Most Common Effects

• Tachycardia and mild hypertension (systolic BP 140-180 mmHg) occur in approximately 30-40% of single-agent overdoses 2
• Nausea and vomiting are frequently reported 1
• Changes in consciousness ranging from somnolence to coma can occur 1
• Mydriasis (dilated pupils) is commonly observed 1

Serious Complications

The FDA label warns that the following severe effects have been reported in venlafaxine (parent drug) overdoses and can occur with desvenlafaxine 1:

• Seizures - occurred in 5% of mixed overdoses but were rare in single-agent desvenlafaxine overdoses 2
• Serotonin syndrome - diagnosed in 9% of cases by treating physicians, though only 1% met formal Hunter Criteria 2
• Cardiac effects including QT prolongation, bundle branch block, QRS prolongation, ventricular tachycardia, and bradycardia 1
• Rhabdomyolysis 1
• Liver necrosis 1
• Death - lethal blood concentrations have been documented at 11.0 µg/mL for desvenlafaxine 3

Dose-Response Relationship

In single-agent overdoses, the median ingested dose was 800 mg (range 250-3500 mg), with most patients experiencing only mild effects 2. However, published studies indicate venlafaxine/desvenlafaxine overdose carries higher fatal outcome risk compared to SSRIs, though lower than tricyclic antidepressants 1.

Critical Management Pitfall

Co-ingestions dramatically increase toxicity risk. Patients taking desvenlafaxine with other medications developed significantly more severe effects including seizures, decreased consciousness (GCS ≤9), and ICU admissions, whereas none of the 75 patients taking desvenlafaxine alone required intensive care 2.

Management Approach

No specific antidote exists for desvenlafaxine 1. The FDA recommends:

• Contact Poison Control Center (1-800-222-1222) immediately for current management recommendations 1
• Assume multiple drug involvement in all cases 1
• Provide standard supportive care including airway management, breathing support, and treatment of hypotension and dysrhythmias 4

Monitoring Requirements

• Continuous cardiac monitoring for QT prolongation, QRS widening, and dysrhythmias 1
• Serial vital signs for hypertension and tachycardia 2
• Neurological assessment for altered consciousness and seizure activity 1, 2
• Assessment for serotonin syndrome using Hunter Criteria if clinically indicated 2