From the FDA Drug Label
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, meperidine, methadone, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i. e., MAOIs [see Contraindications (4) and Drug Interactions (7)] . SSRIs, including escitalopram oxalate, can precipitate serotonin syndrome, a potentially life-threatening condition.
Concomitant use of escitalopram and tricyclic antidepressants (such as amitriptyline) is not recommended due to the increased risk of serotonin syndrome, a potentially life-threatening condition.
- Key risks associated with concomitant use include mental status changes, autonomic instability, neuromuscular symptoms, seizures, and gastrointestinal symptoms.
- Monitoring for symptoms of serotonin syndrome is essential if concomitant use is clinically warranted.
- Alternative treatment options should be considered to minimize the risk of serotonin syndrome. 1 1
From the Research
Patients should generally avoid taking amitriptyline and escitalopram together due to the risk of serotonin syndrome, a potentially serious drug interaction. While some clinicians may prescribe this combination in specific circumstances with careful monitoring, it requires specialist oversight. The interaction occurs because both medications increase serotonin levels in the brain - amitriptyline through multiple mechanisms including serotonin reuptake inhibition, and escitalopram as a selective serotonin reuptake inhibitor. This combined effect can lead to excessive serotonin accumulation, potentially causing symptoms ranging from mild (agitation, tremor, diarrhea) to severe (high fever, seizures, muscle rigidity) 2, 3, 4.
Key Considerations
- The risk of serotonin syndrome is a significant concern when combining these medications, as evidenced by case reports and studies 2, 3, 4.
- If a patient is currently taking both medications as prescribed by their doctor, they should not stop either medication abruptly but should discuss their concerns with their healthcare provider.
- Any symptoms like confusion, rapid heart rate, dilated pupils, muscle stiffness, or high fever while on these medications require immediate medical attention.
- Some studies suggest that combination therapy may be beneficial in specific cases, such as patients with comorbid depression, migraine, and tension-type headache, but this should be approached with caution and close monitoring 5.
Monitoring and Precautions
- Patients taking amitriptyline and escitalopram together should be closely monitored for signs of serotonin syndrome.
- Healthcare providers should be aware of the potential risks and benefits of combination therapy and discuss these with their patients.
- Alternative treatment options should be considered, especially in patients who are at higher risk of serotonin syndrome or who have a history of adverse reactions to these medications.