What are the considerations for adding a medication to Lexapro (escitalopram)?

Adding a Medication to Lexapro (Escitalopram)

Critical Drug Interactions and Contraindications

Before adding any medication to Lexapro, you must absolutely avoid MAOIs (including linezolid) within 14 days, pimozide due to serious cardiac risks, and exercise extreme caution with any serotonergic agents due to potentially life-threatening serotonin syndrome. 1

Absolute Contraindications

• MAOIs: Do not combine within 14 days in either direction due to risk of serotonin syndrome with high fever, muscle spasms, confusion, and loss of consciousness 1
• Pimozide (Orap): Contraindicated due to serious cardiac conduction problems 1

High-Risk Combinations Requiring Intensive Monitoring

Serotonergic Medications - These combinations significantly increase serotonin syndrome risk and require close monitoring within the first 24-48 hours:

• Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine): When combining escitalopram with amitriptyline specifically, start the second medication at low dose and titrate slowly while monitoring for serotonin syndrome symptoms (mental status changes, neuromuscular hyperactivity, autonomic instability) 2, 1
• Triptans for migraine 1
• Tramadol 1
• Lithium 1
• SNRIs (venlafaxine, duloxetine) 1
• Other SSRIs 1
• Amphetamines 1
• Fentanyl 1
• Buspirone 1
• St. John's Wort and tryptophan 1

Cardiac Considerations

For patients requiring tricyclic antidepressants (particularly amitriptyline) with escitalopram:

• Obtain baseline ECG before starting combination, especially in patients over 60 years or with cardiac risk factors 2
• Avoid this combination entirely in patients with cardiac conduction abnormalities or QT prolongation, as amitriptyline prolongs QT interval and delays AV-node conduction (OR = 1.69 for cardiac arrest) 2
• Both escitalopram and amitriptyline can affect cardiac conduction 3, 2

Bleeding Risk Medications

NSAIDs, aspirin, warfarin, and anticoagulants increase bleeding risk when combined with escitalopram due to interference with serotonin reuptake affecting platelet function 1. Monitor for signs of abnormal bleeding 1.

Metabolic Interactions

Escitalopram has minimal CYP450 interactions compared to other SSRIs, making it relatively safer for combination therapy 4. However:

• Cimetidine increases escitalopram exposure by 72% 4
• Omeprazole increases escitalopram exposure by 51% 4
• These increases are generally not considered clinically significant but warrant awareness 4

Protease inhibitors (telaprevir, boceprevir) can decrease escitalopram plasma concentrations, potentially reducing efficacy 3

Monitoring Requirements When Adding Medications

For serotonergic combinations:

• Monitor intensively for serotonin syndrome symptoms during first 24-48 hours after initiation or dose changes 2
• Watch for: agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremor, sweating, diarrhea, fever 2, 1
• If serotonin syndrome develops, immediately discontinue all serotonergic agents and provide supportive hospital-based care 2

For tricyclic antidepressant combinations:

• Consider therapeutic drug monitoring of amitriptyline and nortriptyline plasma levels (therapeutic range 80-200 ng/mL combined) if side effects emerge or response is inadequate 2
• Monitor for anticholinergic effects, particularly in elderly patients 3

Special Population Considerations

Elderly patients:

• Start at approximately 50% of standard adult doses when adding medications 3
• Higher risk for hyponatremia with escitalopram, particularly when combined with other medications 3, 1
• Increased risk of adverse drug reactions overall 3

Patients with hepatic impairment:

• No dose adjustment typically needed for escitalopram 3, 4
• Exercise caution with medications requiring hepatic metabolism 3

Patients with renal impairment:

• No dose adjustment needed for escitalopram 3, 4
• Adjust doses of renally cleared medications accordingly 3

Angle-Closure Glaucoma Risk

Escitalopram can cause mild pupillary dilation, which may precipitate angle-closure glaucoma in susceptible individuals 1. Consider ophthalmologic evaluation before adding medications that also affect pupil size 1.

Practical Algorithm for Adding Medications

1. Screen for absolute contraindications: MAOIs within 14 days, pimozide 1
2. Assess serotonergic burden: Identify all current and proposed serotonergic medications 1
3. Evaluate cardiac risk: Obtain ECG if adding tricyclics or in patients >60 years with risk factors 2
4. Check bleeding risk: Document use of anticoagulants, antiplatelets, NSAIDs 1
5. Start low, go slow: Initiate second medication at reduced dose with gradual titration 2
6. Intensive early monitoring: Assess within 24-48 hours after initiation or dose changes for serotonergic combinations 2
7. Consider therapeutic drug monitoring: For tricyclic combinations if concerns arise 2

Common Pitfalls to Avoid

• Never assume "just a little serotonin" is safe - serotonin syndrome can be life-threatening and develops rapidly 2, 1
• Don't overlook over-the-counter supplements like St. John's Wort or tryptophan, which are potent serotonergic agents 1
• Remember that escitalopram and citalopram should never be co-administered as escitalopram is the active enantiomer of citalopram 1
• Don't forget to counsel patients on alcohol avoidance, as concomitant use is not advised 1