Is it safe to take Lexapro (escitalopram) and Abilify (aripiprazole) together?

Lexapro and Abilify: Safety and Efficacy of Combination Therapy

The combination of Lexapro (escitalopram) and Abilify (aripiprazole) is safe and effective, with no significant drug-drug interactions reported between these medications. 1 According to the FDA drug label, aripiprazole does not require dosage adjustment when co-administered with escitalopram, as they do not have clinically important pharmacokinetic interactions.

Mechanism and Rationale

Lexapro (escitalopram) is a selective serotonin reuptake inhibitor (SSRI) that works by increasing serotonin levels in the brain, while Abilify (aripiprazole) is an atypical antipsychotic that acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at 5-HT2A receptors.

The combination provides complementary mechanisms:

• Escitalopram primarily targets depressive symptoms
• Aripiprazole can augment antidepressant effects and address symptoms that may not respond to SSRIs alone

Clinical Evidence Supporting Combination Use

Recent research supports the safety and efficacy of this combination:

• A 2024 randomized controlled trial found that escitalopram combined with low-dose aripiprazole (5 mg/day) improved cognitive function in patients with major depressive disorder, particularly in executive function and continuous attention domains 2

• A 2009 study demonstrated that the combination of aripiprazole and escitalopram was effective for psychotic major depressive disorder, with a 62.5% response rate and 50% remission rate 3

Side Effect Profile

When used together, potential side effects include:

1. Central nervous system effects: The most common and potentially severe side effects relate to the CNS, including drowsiness and nervousness 4

2. Akathisia: In one study, 10 of 16 subjects developed akathisia with the combination, though 9 of these cases resolved or improved with dose adjustment or propranolol treatment 3

3. Anxiety-related side effects: Patients with pre-existing anxious depression may experience more side effects, particularly nervousness and agitation, when starting escitalopram 4

Important Monitoring Considerations

When using this combination, monitor for:

• Emergence of akathisia, especially during the initial weeks of treatment
• Extrapyramidal symptoms using standardized scales
• Anxiety-related side effects, particularly in patients with pre-existing anxious depression
• QT interval prolongation, though this is not a significant concern with this specific combination

Clinical Recommendations

1. Starting doses:

   • Begin with escitalopram monotherapy (10 mg daily)
   • Consider adding low-dose aripiprazole (2-5 mg daily) if response is inadequate after 4-8 weeks

2. Dose adjustments:

   • Escitalopram can be increased to a maximum of 20 mg daily if needed
   • Aripiprazole can be titrated up to 10-15 mg daily based on response and tolerability

3. Management of side effects:

   • For akathisia: Consider dose reduction or addition of propranolol
   • For anxiety/agitation: Temporary dose reduction may help during initial treatment phase

This combination is particularly valuable for patients with:

• Treatment-resistant depression
• Depression with psychotic features
• Depression with cognitive impairment

Unlike some other medication combinations, there are no significant pharmacokinetic interactions between escitalopram and aripiprazole that would necessitate dose adjustments 1, making this a relatively straightforward combination to manage.