Can Lexapro (escitalopram) and amitriptyline be used together?

Using Lexapro (Escitalopram) and Amitriptyline Together

Lexapro (escitalopram) and amitriptyline can be used together, but caution is required due to the increased risk of serotonin syndrome when combining these two serotonergic medications. 1

Risks of Combination Therapy

• The combination of escitalopram (an SSRI) and amitriptyline (a tricyclic antidepressant) increases the risk of serotonin syndrome due to their overlapping serotonergic effects 1
• Serotonin syndrome symptoms can develop within 24-48 hours after combining medications and include:
  • Mental status changes (confusion, agitation, anxiety) 1
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity) 1
  • Autonomic hyperactivity (hypertension, tachycardia, diaphoresis, shivering) 1
• Advanced symptoms may include fever, seizures, arrhythmias, and unconsciousness, which can be life-threatening 1

Recommendations for Safe Use

• If combination therapy is necessary, start the second medication (whichever is added later) at a low dose and increase slowly 1
• Monitor closely for symptoms of serotonin syndrome, especially during the first 24-48 hours after dosage changes 1
• The FDA label for escitalopram specifically warns about the risk of serotonin syndrome when combined with other serotonergic drugs, including tricyclic antidepressants like amitriptyline 2
• Hospital-based treatment with discontinuation of all serotonergic agents and supportive care is required if serotonin syndrome develops 1

Clinical Considerations

• Escitalopram has less effect on CYP450 isoenzymes compared to other SSRIs, potentially making it a safer choice when combining with other medications 1
• Research has shown that in selected patients who don't respond to monotherapy, the combination of amitriptyline and an SSRI (specifically citalopram, which is similar to escitalopram) can be beneficial for certain conditions without producing major serotonin syndrome symptoms 3
• Patients with comorbid conditions like depression, tension-type headache, or migraine may benefit from this combination when monotherapy is ineffective 3

Monitoring Requirements

• Regular monitoring is essential when using this combination 1, 2
• Patients should be educated about early symptoms of serotonin syndrome and instructed to seek immediate medical attention if they occur 2
• Any worsening of depression, emergence of suicidal thoughts, or unusual changes in behavior should prompt immediate medical evaluation 2
• Consider more frequent follow-up visits during the initial combination period and after any dose adjustments 1

Contraindications

• This combination is contraindicated in patients taking MAOIs or within 14 days of stopping an MAOI 2, 1
• Use extreme caution in patients with a history of seizures, as both medications can lower the seizure threshold 2
• Avoid in patients with cardiac conduction abnormalities or QT prolongation 1

Remember that while this combination can be used with appropriate precautions, the risk of serotonin syndrome is real and requires vigilant monitoring, especially during initiation and dose adjustments 1, 2.