Medications That Can Be Taken With Lexapro (Escitalopram)
Critical Drug Interactions to Avoid
Lexapro should never be combined with MAOIs (monoamine oxidase inhibitors) including phenelzine, isocarboxazid, linezolid, and selegiline, as this combination is absolutely contraindicated due to severe risk of serotonin syndrome. 1
High-Risk Combinations Requiring Extreme Caution
Serotonergic medications pose significant risk when combined with Lexapro and should only be used together with careful monitoring:
Tricyclic antidepressants (amitriptyline, nortriptyline, doxepin): This combination increases serotonin syndrome risk and requires starting at low doses with slow titration 1, 2. The European Society of Cardiology specifically recommends avoiding amitriptyline with escitalopram in patients with cardiac conduction abnormalities or QT prolongation 2.
Other SSRIs/SNRIs (fluoxetine, paroxetine, sertraline, venlafaxine, duloxetine): Combining multiple serotonergic antidepressants substantially increases serotonin syndrome risk 1.
Opioids (tramadol, meperidine, methadone, fentanyl, oxycodone, hydrocodone): These can precipitate hypertensive crisis or serotonin syndrome when combined with Lexapro 1.
Muscle relaxants (cyclobenzaprine/Flexeril): Case reports document serotonin syndrome from this combination 3.
Moderate-Risk Combinations
The following medications can be used with Lexapro but require monitoring:
NSAIDs and aspirin: Increase bleeding risk (ecchymosis, epistaxis, petechiae) when combined with SSRIs 1.
QT-prolonging medications: Escitalopram may interact with drugs that prolong QT interval, requiring ECG monitoring 1, 2.
Sympathomimetic drugs (pseudoephedrine, phenylephrine, amphetamines, albuterol): Risk of hypertensive crisis due to potential MAO inhibition by escitalopram metabolites 1.
Over-the-counter cold medications containing dextromethorphan or chlorpheniramine: These have serotonergic properties and require caution 1.
Safer Medication Options
Escitalopram has minimal CYP450 enzyme effects compared to other SSRIs, making it one of the safer choices for combination therapy 1, 4:
Analgesics: Acetaminophen is preferred over NSAIDs to avoid bleeding risk 1.
Antihypertensives: Can generally be used, though beta blockers and calcium channel blockers may have additive heart rate effects 1.
Immunosuppressants (azathioprine, 6-mercaptopurine): No specific contraindication, though additive immunosuppressive effects should be considered 1.
Monitoring Protocol When Combining Medications
When adding any serotonergic medication to Lexapro:
- Start the second medication at the lowest possible dose 1
- Increase doses slowly over weeks, not days 1
- Monitor intensively for serotonin syndrome symptoms during the first 24-48 hours after any dose change 1, 2
- Watch for mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic instability (hypertension, tachycardia, diaphoresis) 1
For cardiac safety when combining with tricyclics:
- Obtain baseline ECG, especially in patients over 60 years or with cardiac risk factors 2
- Consider therapeutic drug monitoring if side effects emerge 2
Emergency Management
If serotonin syndrome develops, immediately discontinue all serotonergic agents and transfer to hospital for supportive care with continuous cardiac monitoring 1. Advanced symptoms including fever, seizures, arrhythmias, and unconsciousness can be fatal 1.