Can I prescribe Escitalopram (Selective Serotonin Reuptake Inhibitor) and Duloxetine (Serotonin-Norepinephrine Reuptake Inhibitor) together?

From the Guidelines

Prescribing escitalopram and duloxetine together is not recommended due to the risk of serotonin syndrome, and caution is advised when combining any serotonergic medications, as stated in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. When considering the combination of these medications, it's crucial to weigh the potential benefits against the risks, particularly the risk of serotonin syndrome, which can be life-threatening. The guideline emphasizes the importance of caution when starting the second non-MAOI serotonergic drug at a low dose, increasing the dose slowly, and monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes 1. Some key points to consider when prescribing escitalopram and duloxetine together include:

• The potential for drug-drug interactions, particularly with medications that prolong the QT interval or are metabolized by CYP450 isoenzymes
• The risk of discontinuation syndrome when stopping or reducing the dose of either medication
• The importance of careful monitoring for adverse effects, particularly in the first few weeks after starting or changing the dose of either medication
• The need for close specialist supervision and careful monitoring for adverse effects when using combination therapy for treatment-resistant depression Alternative approaches for treatment-resistant depression might include augmentation with medications from different classes, such as atypical antipsychotics, mood stabilizers, or other adjunctive treatments that have lower risks of serotonergic interactions. In general, the combination of escitalopram and duloxetine should be approached with caution, and patients should be closely monitored for any signs of serotonin syndrome or other adverse effects.

From the FDA Drug Label

Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of escitalopram oxalate with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid).

The use of Escitalopram and Duloxetine together may increase the risk of Serotonin Syndrome, as both drugs are serotonergic. It is recommended to exercise caution when co-administering these medications.

• Key Considerations:
  • Monitor patients closely for signs and symptoms of serotonin syndrome.
  • Instruct patients to contact their healthcare provider or report to the emergency room if they experience any signs or symptoms of serotonin syndrome.
  • Consider alternative treatment options or adjust the dosage of one or both medications to minimize the risk of serotonin syndrome 2.

From the Research

Prescribing Escitalopram and Duloxetine Together

• There are no studies that directly assess the safety and efficacy of prescribing Escitalopram and Duloxetine together 3, 4, 5, 6, 7.
• The available studies compare the efficacy and safety of Escitalopram and Duloxetine as separate treatments for major depressive disorder, with some studies suggesting that Escitalopram may be better tolerated than Duloxetine 4, 6, 7.
• One study found that Escitalopram was non-inferior to Duloxetine in acceptability as a second-line treatment for depression 3.
• Another study found that Duloxetine was at least as fast as Escitalopram in terms of antidepressant onset efficacy 5.
• A double-blind comparison study found that Escitalopram was better tolerated and at least as effective as Duloxetine in the treatment of major depressive disorder 6.
• A long-term study found that both Duloxetine and Escitalopram demonstrated similar remission rates over the course of 8 months, with some differences in safety and tolerability measures 7.

Key Findings

• Escitalopram and Duloxetine have different mechanisms of action, with Escitalopram being a selective serotonin reuptake inhibitor and Duloxetine being a serotonin-norepinephrine reuptake inhibitor 4.
• The studies suggest that both Escitalopram and Duloxetine are effective in the treatment of major depressive disorder, but may have different safety and tolerability profiles 4, 6, 7.
• The decision to prescribe Escitalopram and Duloxetine together should be based on individual patient needs and medical history, and should be made with caution due to the lack of direct evidence on the safety and efficacy of this combination 3, 4, 5, 6, 7.